Reference for early detection of cancer

1.      JA Alvarez et al. “Sensitivity of monoclonal antibodies to carcinoembryonic antigen, tissue polypeptide antigen, alpha-fetoprotein, carbohydrate antigen 50, and carbohydrate antigen 19-9 in the diagnosis of colorectal adenocarcinoma”. In: Diseases of the colon & rectum 38.5 (1995), pp. 535–542.


Purpose: This study was designed to establish the sensitivity of monoclonal antibodies to carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), tissue polypeptide antigen (TPA), carbohydrate antigen 50 (CA 50), and carbohydrate antigen 19-9 (CA 19-9) and the efficacy of the joint determination of several tumor markers, as well as the dynamics of postoperative normalization of each marker in the absence of recurrence.

Materials and methods: A prospective study was carried out in 100 patients subjected to surgical resection of colon adenocarcinoma. Serum concentrations of these markers were determined the day before surgery and seven days, two months, and six months after surgery.

Results: The results demonstrate that sensitivity increased as the disease spread and that CA 19-9 was the most sensitive tumor marker. The rate of false negatives was 40 percent for Dukes Stage A lesions, 19 percent for Dukes Stage B, 7 percent for Dukes Stage C, and 0 percent for Dukes Stage D. Determination of two markers (CA 19-9 and CEA) provided the greatest sensitivity in Stages A and D tumors (60 percent and 100 percent, respectively); the incidence did not change when measurements of other antigens were associated. For Stages B and C, determination of at least three markers was necessary, the association of CEA, TPA, and CA 19-9 being that which showed the greatest sensitivity, 78 percent and 91 percent, respectively.

Conclusions: It would be advisable to include monoclonal antibody determination of CEA, TPA, and CA 19-9 in the diagnosis of adenocarcinoma, despite the fact that ultimate sensitivity will depend on the degree of tumor extension or on the presence of metastasis.

2.      A Archimandritis et al. “Serum Protein Markers (Hp, GC, C3) in Patients with Colon Cancer”. In: Human heredity 43.1 (1993), pp. 66-68.

The phenotypes and gene frequencies of three serum protein systems–Hp, GC and C3–were studied in 184 consecutive patients from all over Greece with colon cancer. Healthy Greeks studied previously in our department served as controls. No significant differences were found between patients and controls concerning GC and C3. Significant differences were found in the Hp system; the frequencies of the Hp*1 gene and the Hp 1-1 phenotype were significantly higher in patients than in controls.

3.      RC Bast Jr et al. “CA 125: the past and the future”. In: The International journal of biological markers 13.4 (1998), pp. 179–187.


Over the last 15 years, substantial progress has been made in understanding the potential and the limitations of the CA 125 assay. More than 2000 papers have been published concerning laboratory and clinical studies of CA 125. The original CA 125 assay utilized the OC 125 antibody that recognizes the CA 125 epitope on a high molecular weight glycoprotein. Despite repeated attempts, the gene encoding the peptide component has not yet been cloned. Monoclonal antibodies have been raised against other epitopes expressed by this molecule, leading to the development of the CA 125-II assay that exhibits less day-to-day variation. Using either assay, elevated levels of CA 125 are detected in a number of benign conditions, including endometriosis. CA 125 is most consistently elevated in epithelial ovarian cancer, but can be expressed in a number of gynecologic (endometrial, fallopian tube) and non-gynecologic (pancreatic, breast, colon and lung) cancers. The best established application of the CA 125 assay is in monitoring ovarian cancer. The rate of decline in CA 125 during primary chemotherapy has been an important independent prognostic factor in several multivariate analyses. Persistent elevation of CA 125 at the time of a second look surgical surveillance procedure predicts residual disease with > 95% specificity. Rising CA 125 values have preceded clinical detection of recurrent disease by at least 3 months in most, but not all studies. Given the modest activity of salvage chemotherapy, this information has not yet impacted on survival. Rising CA 125 during subsequent chemotherapy has been associated with progressive disease in more than 90% of cases. CA 125 may serve as an effective surrogate marker for clinical response in phase II trials of new drugs. CA 125 levels can aid in distinguishing malignant from benign pelvic masses, permitting effective triage of patients for primary surgery. Early detection of ovarian cancer remains the most promising application of CA 125. An algorithm has been developed that estimates the risk of ovarian cancer (ROC) based upon the level and trend of CA 125 values. A major trial has been initiated that uses the ROC algorithm to trigger transvaginal sonography and/or subsequent laparotomy. Such a trial could demonstrate improvement in survival through early detection. This strategy should provide adequate specificity, but sensitivity for early stage disease may not be optimal. In the future, improved sensitivity may be attained using multiple markers and neural network analysis. Most serum tumor markers have been proteins or carbohydrates, but lipid markers such as lysophosphatidic acid deserve evaluation. Genomic and proteonomic technologies should identify additional novel markers.

4.      J Bukowski et al. “CA 19-9 and CA 125 antigens in the sera of patients with cancer of the large intestine in relation to its clinical progress”. In: Wiadomosci lekarskie (Warsaw, Poland: 1960) 42.1 (1989), pp. 30–34.


By radioimmunoassay the concentration of the CA 19-9 antigen was determined in the serum of 68 patients with large bowel cancer, while the CA 125 antigen was determined in 26 patients with this disease. Both markers were determined with CIS kits. In all, 127 determinations were done. The results were as follows: 1) CA 19-9 concentration increased with disease progression from 21% (in grade I of local-regional progression, A, B, C according to Dukes), through 41% above-normal results in group II (with metastases–Dukes’ grade D), to 67% in case of recurrence of the tumor, and to 0% in group IV–with absent recurrence sign after radical surgical intervention. 2) CA 125 is without clinical value in large bowel cancer.

5.      P Charpiot et al. “Vitamin A, vitamin E, retinol binding protein (RBP), and prealbumin in digestive cancers.” In: International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitaminund Ernahrungsforschung. Journal international de vitaminologie et de nutrition 59.4 (1989), pp. 323–328.


The existence of a relation between vitamin A and vitamin E and human cancers is supported by epidemiologic investigations. The aim of this study is to link the level of these vitamins to those of plasmatic protein carriers like retinol binding protein (RBP) and prealbumin (TTR), in three groups of subjects: healthy patients (n = 78), polyp (n = 34) and digestive cancer patients (n = 70). A paired t-test did not reveal any significant variation in any parameter between the polyp group and controls, but did evidence a significant decrease in serum levels of retinol (p less than 2.10(-4], RBP (p less than 2.10(-4), TTR (p less than 10(-5), and alpha-tocopherol (p less than 2.10(-3), in cancer cases as against control subjects. Comparison of RBP renal clearance and retinol tissue clearance in cancer and healthy patients indicates that the decrease in circulating retinol levels cannot be attributed to an increase in peripheral consumption. The simultaneous reduction of RBP and TTR serum levels is to be considered as a sign of protein denutrition. Thus our results suggest that the decrease serum levels of vitamins A and E observed in digestive cancers are a consequence of this nutritional deficiency.

6.      Chien-Chih Chen et al. “Is it reasonable to add preoperative serum level of CEA and CA 19-9 to staging for colorectal cancer?” In: Journal of surgical research 124.2 (2005), pp. 169–174.


Background: Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are the most common tumor markers for colorectal cancer. The aim of this study was to evaluate the possibility of adding them into the current staging system by analyzing their prognostic significance.

Materials and methods: The study population was patients (n = 574, 67.1 +/- 11.3 years old, 397 males) who received potentially curative resection of colorectal adenocarcinoma (stage I-III) between January 1994 and August 2002, including preoperative measurements of CEA and CA19-9. Clinicopathological characteristics and associated follow-up data were retrospectively collected by reviewing available medical charts. CEA higher or equal to 5 ng/ml was defined as abnormal (CEA+). The CA19-9 level was set at 37 U/ml (CA19-9+). Patients were further divided into four groups (1, 2, 3, 4) according to the results of these two markers (CEA/CA19-9: -/-, -/+, +/-, and +/+). Survival was analyzed for AJCC staging, CEA (+) versus (-), CA19-9 (+) versus (-), and four groups.

Results: CEA and CA19-9 survival curves were not significantly different. However, the combined use of the two markers revealed a significant survival benefit (P = 0.035) of group 1 (“-” for both markers) over 4 (“+” for both) in stage II.

Conclusions: Patients with an elevated level of both CEA and CA19-9 in stage II of colorectal cancer have a significantly poorer prognosis than those with normal levels of these markers. We recommend adding both CEA and CA19-9 to the current staging system.

7.      P Durdey, NS Williams, and DA Brown. “Serum carcinoembryonic antigen and acute phase reactant proteins in the pre-operative detection of fixation of colorectal tumours”. In: British journal of surgery 71.11 (1984), pp. 881–884.


Fixity of colorectal tumours carries a poor prognosis, but only if it is the consequence of malignant spread. Pre-operative radiotherapy may be beneficial but selection depends on clinical examination which is often inaccurate or impossible. We therefore investigated if serum concentrations of carcinoembryonic antigen and acute phase reactant proteins (APRPS) which may be elevated in patients with colorectal cancer could determine the degree and nature of local spread prior to operation. Carcinoembryonic antigen (CEA), alpha 1 acid glycoprotein (AGP) and C-reactive protein (CRP) were measured pre-operatively in 100 patients with colorectal tumours, 89 of whom had a carcinoma. Thirty-two (36 per cent) were fixed, 18 (56 per cent) by malignancy (FM) and 14 (44 per cent) by inflammation (FI). Levels of CEA, AGP and CRP were all significantly higher in the serum of patients with fixed tumours (P less than 0.05). Concentrations of AGP greater than 1.4 g/l or CRP greater than 15 mg/l were accurate predictors of tumour fixation (specificity 87 and 90 per cent; sensitivity 78 and 78 per cent. CEA appeared more accurate in determining the nature of fixation. A value of greater than 50 ng/ml predicted 82 per cent of FM tumours (specificity 100 per cent; sensitivity 87 per cent). Thus, pre-operative measurement of serum CEA and APRP appear able to predict fixation of colorectal tumours.

8.      G Gebauer and W Müller-Ruchholtz. “Tumor marker concentrations in normal and malignant tissues of colorectal cancer patients and their prognostic relevance.” In: Anticancer research 17.4A (1997), pp. 2731–2734.


Tumor markers CEA, CA19-9, CA15-3, CA125, AFP, beta-HCG, SCC were measured quantitatively in the serum, tumor tissue and healthy colonic mucosa of patients with colorectal cancer. We wanted to investigated whether there is a difference in concentration between patients with and without recurrence of cancer. During the follow-up period 14 of 38 patients showed tumor recurrence. The patients with cancer relapse had higher preoperative serum levels of CEA and CA19-9 and in the histologically normal colonic mucosa they had higher concentrations of CEA, CA19-9, SCC and low CA15-3. The highest values of CEA, CA19-9, and SCC occurred in the mucosa of patients developing local cancer recurrence. Marker concentrations in tumor tissues themselves did not differ between patients with or without tumor relapse. Though confirmation in a larger number of cases is needed we conclude from these results that tumor marker concentrations in the healthy colonic mucosa of patients with colorectal cancer may become valuable indicators of the risk of tumor recurrence.

9.      Lisa J Herrinton et al. “Transferrin saturation and risk of cancer”. In: American journal of epidemiology 142.7 (1995), pp. 692–698.


The authors examined the hypothesis that relatively high levels of transferrin saturation increase the risk of cancer. They studied a cohort of prepaid health plan members whose transferrin saturation levels were measured during the period 1969-1971 and who were followed for cancer through 1990. After the exclusion of 10 percent of the subjects who received treatment for one or more of six chronic conditions or who were pregnant when the measurement was made and persons who contributed less than 5 years of follow-up, the authors were left with 38,538 persons who were followed for an average period of 17.7 years. In women, a positive association was observed between transferrin saturation and risk of stomach carcinoma (> or = 34.5% compared with < or = 20.3%: relative risk (RR) = 3.5, 95% confidence interval (CI) 0.98-12). In men, transferrin saturation was inversely associated with risk of colon and rectal carcinoma (> or = 40.7% compared with < or = 26.0%: colon, RR = 0.62, 95% CI 0.35-1.1; rectum, RR = 0.30, 95% CI 0.08-1.1) and with non-Hodgkin’s lymphoma (32.1-40.6% compared with < or = 26.0%: RR = 0.31, 95% CI 0.11-0.88; no cases observed with transferrin saturation > or = 40.7%). The authors did not find evidence that the risk of epithelial cancer (all sites combined) was related to transferrin saturation level or to iron deficiency (< or = 15%) or overload (> or = 60%).

10.    Christian Kersten et al. “Increased C-reactive protein implies a poorer stage specific prognosis in colon cancer”. In: Acta oncologica 52.8 (2013), pp. 1691–1698.


Background: To characterize the stage-specific prognostic relevance of preoperative systemic inflammatory response, defined by C-reactive protein (CRP), in colon cancer (CC) patients.

Material and methods: Data from CC patients operated on from 1998 to 2007 at three hospitals from three different Nordic countries were collected retrospectively from national registries, local databases and/or patient records. Patients with emergency surgery, infection or auto-immune disease were excluded. Associations between clinical or histopathological variables and CRP were assessed. Patients were followed from the date of surgery to death or end of follow-up. Disease-specific survival (DSS) was the main endpoint.

Results: In total, 525 patients with age and stage distributions which were representative for CC patients were included. None of the patients was lost to follow-up. Age, TNM Stage, WHO differentiation grade and right-sided tumor location significantly associated with elevated CRP values, in contrast to postoperative morbidity, which did not. CRP levels were found to be a strong prognostic factor for DSS in CC. The risk of death due to CC was augmented with increasing levels of CRP in every stage of operated CC. Both short- and long-term DSS were impaired. The sub-hazard ratios for CRP-levels above 60 mg/L were 7.37 (CI 2.65-20.5) for stage I+ II, compared to 3.29 (CI 1.30-8.29) for stage III and 2.24 (CI 1.16-4.35) for stage IV.

Conclusion: Increase of CRP concentrations correlate with clinically relevant poorer disease-specific survival in each stage of CC.

11.    Teruyuki Kishida et al. “Clinical significance of serum iron and ferritin in patients with colorectal cancer”. In: Journal of gastroenterology 29.1 (1994), pp. 19–23.


To clarify the significance of serum iron and ferritin as indicators of iron loss caused by continuous bleeding, and, thus, to determine their value as markers of colorectal cancer, values for the two were compared in male patients with early and advanced colorectal cancer and age-matched male controls. The mean value of serum iron levels in patients with advanced colorectal cancer was significantly decreased compared with values in patients with early colorectal cancer and controls, 50.5 +/- 38.6 micrograms/dl vs 93.0 +/- 32.1 micrograms/dl and 107.1 +/- 32.9 micrograms/dl, respectively (p < 0.001). The mean value of serum ferritin levels in patients with early and advanced colorectal cancer was also significantly decreased compared with controls, 80.5 +/- 35.0 ng/ml (p < 0.01) and 48.8 +/- 72.8 ng/ml (p < 0.001), respectively, vs 117.1 +/- 46.8 ng/ml. However, there was no significant difference between mean serum iron levels in patients with early colorectal cancer and controls. Eighteen (78.3%) of the 23 patients with advanced colorectal cancer and 3 (16.7%) of the 18 patients with early colorectal cancer had serum iron levels below 85 micrograms/dl and serum ferritin levels below 60 ng/ml. Levels of both serum iron and ferritin, without clinically evident anemia, are useful indicators of advanced colorectal cancer.

12.    Ken Konishi et al. “Expression of C4. 4A at the invasive front is a novel prognos tic marker for disease recurrence of colorectal cancer”. In: Cancer science 101.10 (2010), pp. 2269–2277.


Metastasis-associated gene C4.4A is a glycolipid-anchored membrane protein expressed in several human malignancies. The aim of this study was to explore the expression and clinical relevance of C4.4A in colorectal cancer. By quantitative RT-PCR, 154 colorectal cancer tissues were examined for C4.4A mRNA. We examined 132 colorectal cancer tissues by immunohistochemistry using a new polyclonal antibody that recognizes the C4.4A protein C-terminus containing the glycosylphosphatidyl-inositol anchor signaling sequence. A significant difference in 5-year overall survival was found between samples with high and low expression of C4.4A mRNA (P = 0.0005). Immunohistochemistry showed strong membranous staining of C4.4A at the invasive front of colorectal cancer tumors and at the frontier of metastatic lesions to lymph node and lung. The membranous staining with enhanced intensity at the invasive front of the primary colorectal cancer (Type A: 34/132, 25.6%) was associated with depth of invasion (P = 0.033) and venous invasion (P = 0.003), and was a significant independent prognostic factor (5-year overall survival in the entire series [n = 132; P = 0.004] and disease-free survival in stage II and III colorectal cancers [n = 82; P = 0.003]). Moreover, Type A C4.4A expression was linked to shorter liver metastasis-free survival rate, lung metastasis-free survival rate, or hematogenous metastasis-free survival (P = 0.0279, P = 0.0061, and P = 0.0006, respectively). Our data indicate that expression of the C4.4A protein at the invasive front acts as a novel prognostic marker in colorectal cancer, possibly through invasion-related mechanisms.

13.    P Kuusela et al. “Comparison of CA 19-9 and carcinoembryonic antigen (CEA) levels in the serum of patients with colorectal diseases”. In: British journal of cancer 49.2 (1984), p. 135.


The serum levels of CA 19-9 and carcinoembryonic antigen (CEA) were determined in 37 patients with benign colorectal diseases and in 111 patients with newly discovered colorectal carcinomas or clinically verified relapses. In cancer patients, the CA 19-9 level ranged from normal (0-37 U ml-1) to 77,500 U ml-1 whereas all samples but one from patients with benign colorectal diseases had a normal value. CA 19-9 was increased in 46% and 45% of patients with an advanced (Dukes C or D) carcinoma or a verified recidive, respectively. Only one out of 26 patients (4%) with a localized (Dukes A or B) carcinoma displayed an elevated CA 19-9 level (greater than 37 U ml-1). No clear correlation was found between the CA 19-9 and CEA levels. The sensitivity of the CA 19-9 test (36%) was poorer than that of the CEA assay (69%), but the new test was markedly more specific (97% vs 70%) than the CEA assay.

14.    Feng Li, Teruyuki Kishida, and Masafumi Kobayashi. “Serum iron and ferritin levels in patients with colorectal cancer in relation to the size, site, and disease stage of cancer”. In: Journal of gastroenterology 34.2 (1999), pp. 195–199.


We investigated blood loss from colorectal cancer in 92 men seen between January 1990 and June 1997, in relation to the size and site of the tumor, Dukes stage, pathologic type of cancer, and serum carcinoembryonic antigen (CEA) positivity. We used indirect methods, measuring serum hemoglobin, iron, and ferritin concentrations. The means of these three concentrations were significantly lower in patients with a tumor >3cm than in those with a tumor < or =3cm in largest diameter. The means of the three values were lower in patients with proximal colon cancer than in those with distal colon cancer, but only the difference in serum hemoglobin concentration was significant. Cancers of the ulcerative type were found more often in the proximal colon. The proportion of patients with Dukes stage C or D was not different between those with proximal colon cancer and those with distal colon cancer. There was a positive correlation between tumor size and Dukes stage. There were no differences in serum hemoglobin, iron, and ferritin concentrations with respect to the pathologic type of cancer and CEA positivity. These findings show that blood loss from colorectal cancer is closely related to the size and site of the tumor.

15.    G Lindmark et al. “Limited clinical significance of the serum tumour marker Ca 72-4 in colorectal cancer.” In: Anticancer research 16.2 (1996), pp. 895–898.


Background: We explored the potential value of CA 72-4 in the staging and prognostic prediction of colorectal cancer, as compared to six previously investigated serum tumour markers – CEA, CA 19-9, CA 50, CA 242, TPA, and TPS.

Materials and methods: CA 72-4 was analysed using an immunoradiometric assay in serum samples obtained, prior to surgery, from 196 consecutive patients resected between Jan. 1987 and Nov. 1992.

Results: CA 72-4 levels increased with progressive tumour stages; a high level correlated with poor prognosis. However, the information obtained from CA 72-4 did not improve the ease of staging, as compared with other tumour markers. Various combinations of CA 72-4 with the other tumour markers did not add any substantial information to the staging process either. The value of the CA 72-4 in prognostic prediction, as shown in the univariate analysis, was limited in the multivariate tumour marker analyses.

Conclusions: CA 72-4 does not improve the staging and prognostic prediction of colorectal cancer, when compared with other serum tumour markers used.

16.    OC Lunde and O Havig. “Clinical significance of carcinoembryonic antigen (CEA) in patients with adenocarcinoma in colon and rectum.” In: Acta Chirur gica Scandinavica 148.2 (1982), pp. 189–193.


Determination of carcinoembryonic antigen (CEA) in serum has been performed in 253 patients with proved adenocarcinoma in the colon and rectum. Preoperative CEA was normal in 58.3% of the patients. A correlation between CEA level and Dukes’ grading was found. There was, however, no statistically significant difference in recurrence rate between patients with normal and patients with elevated pre-operative CEA. Transient CEA elevation was seen in the follow-up period after curative resection in 21.8%. 75% of the patients with recurrence had abnormal CEA, and CEA elevation was the first sign of recurrence in 59.1%. The majority of these patients, however, had advanced disease not available for surgical treatment. In cases with local resectable tumour CEA often was normal. Only a few patients had advantage of CEA determination for diagnosis of recurrence and its routine use is therefore questioned.

17.    A Mangano et al. “Complelent and Its Fractions (C3-C4) Pattern in Subjects with Msoplasia”. In: Journal of immunopharmacology 6.3 (1984), pp. 147-162.


The total complement (CH50) and its fractions C3 and C4 have been assayed for up to two years after surgery in subjects with breast, gastric and colon-rectum carcinomas. In all three types of pathology a constant pattern has been observed. Before surgery the CH50 stayed below the normal range but was increased following surgery. After a month it was again within the normal range and subsequently, according to the clinical evolution of the disease, it remained normal in those patients without relapse or any apparent metastasis, whereas in those patients who displayed metastasis and/or approached the terminal phase it fell below the normal range. The C3 fraction followed the CH50 pattern whereas the C4 did not show any variation correlated with the stages of the disease.

18.    Gerard Milano et al. “Serum prealbumin, retinol-binding protein, transferrin, and albumin levels in patients with large bowel cancer”. In: Journal of the National Cancer Institute 61.3 (1978), pp. 687–691.


In a study of the levels of serum prealbumin (PALB), retinol-binding protein (RBP), transferrin (TF), and albumin (ALB) in patients with large bowel cancer, critical values were established as (g/liter): PALB, 0.15; RBP, 40 X 10(-3); TF, 2.0; and ALB, 30. Values consistently below these were taken as a sign of malnutrition. The proteins in this system were interrelated and tended to show a similar pattern of change. Metastatic colon cancer caused a relatively small decline of ALB compared to the mean in tumor-free patients. PALB was the most sensitive indicator of nutrition, and its levels and rates of change had a prognostic significance. A rapid fall of PALB often occurred 2–3 months prior to the patients’s death; this preterminal phase in ambulant patients was frequently heralded by a progressive rise in the level of C-reactive protein in the absence of any obvious infection.

19.    L Molnar et al. “Correlation between the results of carcinoembryonal antigen (CEA) test and the clinical stage of colorectal carcinoma.” In: Acta chirurgica Hungarica 27.1 (1986), pp. 27–34.


Correlation between results of CEA test and clinical stage of colorectal carcinoma is described. No correlation was found between the different stages and the actual CEA titre. Normalization of an increased preoperative serum CEA level indicated, however, nearly always the radical character of the intervention. Critically high (above 30 ng/per ml) CEA value observed in Dukes’ stages C and D can be considered bad prognostic signs. Patients like these died within one year. Results of CEA tests are also useful complementary data contributing to the diagnosis of recurrence or distant metastases.

20.    Seung-Jae Myung. “Colon tumor and inflammation: is C-reactive protein possible colon tumor marker?” In: The Korean Journal of Gastroenterology 51.4 (2008), pp. 265–268.

Comment on

21.    Tohru Nakagoe et al. “Prognostic value of carcinoembryonic antigen (CEA) in tumor tissue of patients with colorectal cancer.” In: Anticancer research 21.4B (2001), pp. 3031–3036.


To establish the prognostic value of carcinoembryonic antigen (CEA) concentration in tumor tissue (T-CEA), normal colonic mucosa (N-CEA) and pre-operative serum (S-CEA), we studied 79 patients who underwent resections for colorectal cancer. The patients were separated into groups reflecting laboratory values lower or higher than a diagnostic value (S-CEA) or the median value of the entire population (T-CEA, N-CEA). A high S-CEA predicted for more advanced stage (p = 0.028), whereas no association was noted between stage and CEA concentration for T-CEA and N-CEA groups. The high S-CEA and T-CEA groups had a worse clinical outcome (p=0.0036 and p=0.024, respectively), while survival of high versus low N-CEA groups did not differ. By Cox’s regression analysis, high T-CEA concentration was an independent variable for poor outcome (Hazard ratio, 3.15), while S-CEA and N-CEA were not. In conclusion, a high T-CEA concentration was the only independent predictor of poor outcome after resection for colorectal cancer.

22.    Shivananda B Nayak et al. “Copper and ceruloplasmin status in serum of prostate and colon cancer patients”. In: Indian journal of physiology and pharmacology 47.1 (2003), pp. 108–110.


Serum copper and ceruloplasmin levels were estimated in 20 patients each of prostate and colon cancer. Although copper to ceruloplasmin ratio was not significantly altered, copper and ceruloplasmin levels were increased significantly in the cancer patients as compared to controls. Trace elements and free radicals have been implicated in the etiology of cancer. Hence determination of specific antioxidants (like ceruloplasmin) and trace elements (like copper) may be of value in the early diagnosis of prostate and colon cancer.

23.    Richard L Nelson. “Iron and colorectal cancer risk: human studies”. In: Nutrition reviews 59.5 (2001), pp. 140-148.


Some reports have associated iron with cancer risk, particularly of the colorectum. This review will focus on the human studies that have investigated this association. Comparative studies were sought in which people with and without colorectal neoplastic lesions, either cancers or adenomatous polyps, were assessed for iron exposure. Iron exposure variables included dietary iron intake, iron vitamin supplementation, body iron stores as measured by ferritin or transferrin saturation, and gene status for hereditary hemochromatosis. Medline was searched for published reports using the key words iron, cancer, colon, rectum, ferritin, transferrin, and hemochromatosis. In addition, the Cochrane Library was searched for relevant studies and several authors were contacted to investigate their awareness of unpublished studies. Studies were categorized by study design and ranked for quality of innovation in design, sample size, and thoroughness of iron status ascertainment. Thirty-three studies were reviewed in 26 publications. Of the larger studies, approximately three-quarters supported the association of iron, in all three strata of exposure, with colorectal neoplasia risk. Because iron is broadly supplemented in the American diet, the benefits of iron supplementation need to be measured against the long-term risks of increased iron exposure, one of which may be increased risk of colorectal cancer.

24.    Tadahiro Nozoe et al. “Increase in both CEA and CA19-9 in sera is an inde pendent prognostic indicator in colorectal carcinoma”. In: Journal of surgical oncology 94.2 (2006), pp. 132–137.


Background and objectives: Carcinoembryonic antigen (CEA) and carbohydrate antigen (CA19-9) are well known to be the most common tumor markers of colorectal carcinomas. However, the significance of increase in these markers to predict the prognosis of the patients remains a problem for debate.

Methods: One hundred three patients with colorectal carcinoma, who had been treated by resection and reconstruction of digestive tracts were studied. Correlation of preoperative serum value of CEA and CA19-9 with clinicopathologic features including prognosis of the patients was investigated.

Results: Preoperative elevation of both of the two markers proved to be an independent prognostic indicator, however, an elevation of only one of the two markers did not obtain a prognostic significance.

Conclusions: Combined data of preoperative increase in CEA and CA19-9 in sera can provide a powerful and useful information to predict prognosis of patients with colorectal carcinoma.

25.    Seung-Yeol Park et al. “N-glycosylation status of B-haptoglobin in sera of patients with colon cancer, chronic inflammatory diseases and normal subjects”. In: International journal of cancer


N-glycosylation status of purified beta-haptoglobin from sera of 17 patients, and from sera of 14 healthy volunteer subjects, was compared by blotting with various lectins and antibodies. Patients in this study were diagnosed as having colon cancer through histological examination of each tumor tissue by biopsy. Blotting index of serum beta-haptoglobin with Aleuria aurantia lectin (AAL) was clearly higher for cancer patients than for healthy subjects. No such distinction was observed for blotting with three other lectins and two monoclonal antibodies. To determine tumor-associated reactivity of AAL binding as compared to inflammatory processes in colonic tissues, beta-haptoglobin separated from sera of 5 patients with Crohn’s disease (CD), and 4 patients with ulcerative colitis (UC), was studied. All these cases, except one case of UC, showed AAL index lower than that in cancer cases, similarly to healthy subjects. The higher AAL binding of beta-haptoglobin in colon cancer patients than in healthy subjects appeared to be due to alpha-L-fucosyl residue, since it was eliminated by bovine kidney alpha-fucosidase treatment. N-linked glycans of serum haptoglobin from colon cancer patients vs. healthy subjects were released by N-glycanase, fluorescence-labeled, and subjected to normal-phase high performance liquid chromatography (NP-HPLC). Glycan structures were determined based on glucose unit (GU) values and their changes upon sequential treatment with various exoglycosidases. Glycosyl sequences and their branching status of glycans from 14 cases of serum beta-haptoglobin were characterized. The identified glycans were sialylated or nonsialylated, bi-antennary or tri-antennary structures, with or without terminal fucosylation.

126.1 (2010), pp. 142–155.

26.    Bo E Persson et al. “A clinical study of CA-50 as a tumour marker for monitoring of colorectal cancer”. In: Medical oncology and tumor pharmacotherapy 5.3 (1988), p. 165.


Using a radioimmunoassay we have determined serum levels of the carcinoma-associated antigen CA-50 in 266 patients with colorectal cancer. Elevated CA-50 levels were found in Dukes’ A (15%), Dukes’ B (43%), Dukes’ C (31%) and Dukes’ D (65%). Patients who had developed a recurrence had 66% elevated levels. 25% of resected patients with no evidence of disease also had elevated CA-50 levels. From 139 patients operated on for a Dukes’ A-C, a rise in CA-50 levels from the pre- to the 6-9 month post-operative sample was demonstrated in 12 cases in the absence of any clinical evidence for a recurrence. On follow-up, a recurrence later developed in all these cases with lead times of CA-50 titre rises ranging from 5 to 40 months. A rise in CA-50 levels after resection of a Dukes’ A-C is indicative of a recurrence and may precede any clinical evidence of disease by several months or years. Data is also presented from 552 cases with colorectal cancer analysed with a immunoradiometric assay.

27.    Maja Prutki et al. “Altered iron metabolism, transferrin receptor 1 and ferritin in patients with colon cancer”. In: Cancer letters 238.2 (2006), pp. 188–196.


In this study, the level and distribution of transferrin receptor 1 (TfR1) and ferritin in colorectal carcinoma and in normal colon epithelium has been determined relative to the tumor stage and iron status of patients using immunohistochemical staining methods. While the majority of carcinoma patients were anemic, no relationship between the level of colon tissue ferritin and TfR1 and the systemic parameters of iron metabolism was evident. Furthermore, no association between ferritin content and the grade of colorectal carcinoma was observed. However, a relationship between the expression of TfR1 and the grade of colorectal carcinoma was observed. In this case high expression of TfR1 was found in colorectal carcinoma samples of Dukes A or B grade, and well differentiated colorectal carcinoma cells. In comparison, weak or no expression of TfR1 was observed in carcinoma samples of Dukes C or D grade with poorly differentiated cells and in carcinoma samples that had lymph node infiltration and distant metastasis.

28.    Henning Putzki et al. “Comparison of the tumor markers CEA, TPA, and CA 19-9 in colorectal carcinoma”. In: Cancer 59.2 (1987), pp. 223–226.


In 103 patients with colorectal carcinoma carcinogenic antigen, 19-9 (CEA), tissue polypeptide (TPA) and carbohydrate antigen (CA 19-9) were measured in serum. The values determined in these patients and in a control group have been converted into specificity-sensitivity diagrams. Comparison of diagrams of the three markers showed that CEA has the greatest sensitivity in colorectal carcinoma. Different ways to enhance the sensitivity by combination of the markers have been tried. By combination, however, the sensitivity of the single markers is not essentially enhanced.

29.    Armin Quentmeier et al. “Carcinoembryonic antigen, CA 19-9, and CA 125 in normal and carcinomatous human colorectal tissue”. In: Cancer 60.9 (1987), pp. 2261–2266.


In 115 primary colorectal carcinomas and 64 normal colorectal mucosa specimens the concentrations of carcinoembryonic antigen (CEA), CA 19-9, and CA 125 were measured. The determinations were performed in cytosols by use of radioimmunometric and enzymeimmunometric assays and related to the wet tissue weight. In the cancer tissue the CEA levels ranged from 5.5 to 1990 micrograms/g tissue and were significantly higher (P less than 0.0001) than those found in the normal mucosa (1.2-58.6 micrograms/g). The CA 19-9 content in carcinoma specimens (120-72660 U/g) was also significantly higher (P = 0.011) than in the normal mucosa (37-5800 U/g). In contrast, no significant difference of the CA 125 concentrations between the normal and the cancer tissue was found. The relative operating characteristic (ROC) curves for the three markers corroborate CEA as the marker superior to CA 19-9. On the other hand is shown that CA 125 is completely unable to discriminate between normal and cancer tissues. A decreasing CEA tissue concentration and an increasing dedifferentiation of colorectal cancers were significantly (P = 0.018) related with each other. Higher tumor stages implied significantly higher tissue marker values of CA 19-9 (P = 0.027) and CA 125 (P = 0.0008). The findings correspond quite well with serum examinations of the three markers which have been reported earlier.

30.    M Rosandić-Pilas et al. “Relationship between tissue and serum concentrations of carcinoembryonic antigen (CEA) in gastric and colonic carcinomas.” In: Acta medica Austriaca 17.5 (1990), pp. 89-93.


A relationship between tissue and serum concentrations of carcinoembryonic antigen (CEA) as determined by monoclonal enzymo-immunoassay (EIA) was studied in 47 patients with gastric carcinoma and 46 patients with colorectal carcinoma. The values were then compared to those obtained in a control group of 64 healthy subjects. On the basis of results, an increase in tissue CEA is not paralleled by a simultaneous increase in serum CEA. Serum CEA depends on tumor mass and points to the process extension. There is no specific tissue CEA threshold above which the serum CEA concentration should unavoidably increase. A relationship between tissue and serum CEA concentrations according to the degree of differentiation, studied in colorectal carcinomas, revealed significantly lower values of tissue CEA concentration in poorly differentiated carcinomas, whereas serum CEA concentrations did not show any such difference. The present study has suggested that, having identified both tissue and serum CEA concentrations in colorectal carcinoma, the tumor, its size and differentiation could be readily and quite closely defined at the time of measurements.

31.    YT Van der Schouw et al. “Comparison of four serum tumour markers in the diagnosis of colorectal carcinoma”. In: British journal of cancer 66.1 (1992), p. 148.


The assessment of the diagnostic power of four serum tumour markers, CEA, CA 19-9, CA 50 and CA 195 for colorectal carcinoma is described, according to recently formulated guidelines. Preoperative serum concentrations of the four markers were determined in 198 colorectal cancer patients and 57 patients with a benign colorectal disorder. The cumulative frequency distributions of the malignant and benign group show strong overlap for all markers, which indicates low diagnostic ability. This is confirmed by the Receiver Operating Characteristic curves, which have areas under the curve of 0.65 (95% confidence interval (CI) 0.58-0.73) for CA 19-9, CA 50 and CA 195 and of 0.70 (95%) CI 0.63-0.77) for CEA. The new tumour markers appear to be of slightly less diagnostic value than CEA for the primary diagnosis of colorectal cancer, although the discrepancy is not statistically significant. The low diagnostic power of CA 19-9, CA 50 and CA 195 may be due to a high proportion of colorectal cancer patients having the Lewis(a-b-) phenotype, who cannot synthesise these markers.

32.    Jian-qiu Sheng et al. “Transferrin dipstick as a potential novel test for colon cancer screening: a comparative study with immuno fecal occult blood test”. In: Cancer Epidemiology and Prevention Biomarkers 18.8 (2009), pp. 2182–2185.


Recent proteomic studies identified Transferrin (Tf) as a potential biomarker for cancer. We examined the efficacy of the newly developed Tf dipstick for detecting colorectal cancer and premalignant lesions, and compared that to Immuno Fecal Occult Blood test (IFOBT). Fecal samples from 110 patients including 40 colorectal cancer, 36 premalignant subjects (including 16 with high-risk adenomas and 20 with ulcerative colitis), and 34 low-risk subjects were collected before colonoscopic examination. Compared with IFOBT, Tf had a significantly higher positive rate in patients with colorectal cancer and premalignant lesions (76% for Tf versus 61% for IFOBT, respectively; chi(2) = 4.38; P < 0.05). The difference of positivity was mainly observed in patients with premalignant lesions (72% for Tf versus 44% for IFOBT; chi(2) = 5.71; P < 0.05), whereas the positive rates in cancer group and in low-risk group were similar (both P > 0.05). Combining Tf with IFOBT together (either/or) had 90% positive rate in cancer patients, 78% in premalignant patients, and 29% in low-risk subjects. The overall accuracy of IFOBT and Tf tests for detecting colorectal cancer and premalignant lesion was 69.0% and 76.4%, respectively. Tf dipstick test seems to be a highly sensitive test for detecting not only cancer, but also premalignant lesions, and provides an additional tool for colorectal cancer screening.

33.    Colin Walker and Bruce N Gray. “Acute-phase reactant proteins and carcinoem bryonic antigen in cancer of the colon and rectum”. In: Cancer 52.1 (1983), pp. 150–154.


One hundred and twenty-eight patients bearing primary malignancies of the large bowel were studied to ascertain the value of acute-phase reactant proteins (serum protein hexose, ceruloplasmin, transferrin, alpha-1-antitrypsin, seromucoid and haptoglobin) either alone or in conjunction with carcinoembryonic antigen to accurately reflect the disease status of patients both before and after resection of their large bowel malignancy. The results indicate that acute-phase reactant proteins have a higher diagnostic rate for the presence of malignancy than does CEA. Estimation of the serum protein hexose alone is of greater diagnostic value than a combination of acute-phase reactant proteins. Furthermore, serum protein hexose and CEA are complementary and when combined will reflect the presence of malignancy in a greater number of patients than either one alone. Following resection of primary large bowel cancer, acute-phase reactant proteins are as accurate as CEA in evaluating the disease-free status of patients and furthermore when combined with CEA increased the predictive value for the detection of patients with recurrent disease.

34.    V Yasasever et al. “Serum values of CA72. 4 in patients with gastrointestinal system tumors comparison with CEA and CA 19.9.” In: European journal of gynaecological oncology 13.5 (1992), pp. 403–408.


Serum CA 72.4 levels of patients with malignant gastrointestinal disorders (n = 77) were determined in parallel with the CEA and CA 19.9 levels. The values related to healthy individuals were 1.7 U/ml, with a median of 1.7 U/ml, whereas an average of 12.1 U/l (median 2 U/ml) was measured in malignancy. Among all three markers CEA showed the highest positive rate while the values for CA 19.9 and CA 72.4 were lower. Although positive rates among the healthy group were observed with CEA and CA 19.9, no false positives were found with CA 72.4. Elevated CA 72.4 levels were found in 17.6% of patients with gastric carcinoma and 56.3% with colorectal carcinoma. All markers showed significant sensitivity for the malignant state when used alone. However, the regression analysis revealed that only the combination of CA 72.4 and CEA may contribute significantly to the diagnostic potential. Our results indicate that complementation of CEA with CA 72.4 can significantly increase the sensitivity in the serodiagnosis of gastrointestinal system cancers. Combination of positive information from these two sources is likely to lead to a more accurate diagnosis and may therefore improve the efficiency of the follow-up and therapeutic response.

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