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Background: We aimed to assess the prognostic value of CYFRA 21-1 in a series of patients with anal canal squamous cell carcinoma treated by radiation-based therapy., Methods: All patients with anal cancer referred between September 2005 and July 2013 were considered. Patients with diagnosis of anal squamous cell carcinoma and in whom pre- and post-treatment serum CYFRA 21-1 levels were available were included. Serum CYFRA 21-1 levels at initial workup and after therapy were collected. Survival rates were estimated using the Kaplan-Meier method. Cox regression analysis was used to evaluate prognostic variables for prediction of outcomes., Results: Eighty-two patients were included. Median follow-up was 60 months (range: 8-128). Pre-treatment serum CYFRA 21-1 levels were significantly correlated with tumour stage (p < 0.001). Normal post-treatment serum CYFRA 21-1 level was significantly correlated with tumour complete response (p = 0.004). Elevated post-treatment serum CYFRA 21-1 level was significantly associated with poorer progression-free survival (p = 0.02) and overall survival (p = 0.003). T stage and post-treatment serum CYFRA 21-1 were independent prognostic factors for overall survival (p = 0.04 and 0.03, respectively)., Conclusions: Serum CYFRA 21-1 appears to be a useful marker for the monitoring of anal squamous cell carcinoma patients. Elevated post-treatment value appears to be correlated with treatment failure.

Increased serum levels of human chorionic gonadotropin beta subunit (hCG beta) were described previously in patients with bladder cancer. To obtain insight into such production of hCG beta, the expression of hCG beta 7, 8, 5, and 3 genes in bladder carcinomas and normal urothelia was investigated by reverse transcription PCR. Surprisingly, hCG beta mRNAs were detected in both normal urothelial and carcinomatous cells. However, tumor progression was characterized by different patterns of transcription of the hCG beta genes; the beta 7 gene was the only gene transcribed in normal urothelia and Ta tumors included in this study, whereas in addition to beta 7, genes beta 5, 8, and 3 were transcribed in T1 to T4 tumors. Moreover, transcription levels of the latter three genes increased with the stage of the disease. These observations showed that dramatic modifications in the expression of hCG beta genes accompany progression of bladder carcinomas.

The clinical use of tumor-associated markers still raises several problems, due to the lack of specificity of most biological markers and to insufficient evaluation of their true benefit for the patients. Only two markers, calcitonin and alpha-fetoprotein, markers of medullary thyroid carcinomas and of hepatocellular carcinomas respectively, have been proved useful in screening high risk populations for tumors. The usefulness of the prostate specific antigen in screening for prostatic cancer is still debated. Human chorionic gonadotropin and its free beta subunit are useful in the early detection of testicular cancer. Other biological makers, such as CA 15-3 for breast cancers, CA 19-9 for either gastric or pancreatic cancers, anc CA 125 for ovarian tumors are useful mostly in the follow-up of these tumors. Finally, measurements of tumor markers and analysis of their results must be performed by biologists or physicians who use tumor-associated markers routinely.

Due to their extreme specificity, monoclonal antibodies (Mabs) have been very useful for new analytical progresses in the field of tumor markers. For example, it has been possible to analyse only calcitonin, independently of its precursors in the patients with medullary thyroid carcinomas. These precursors have been estimated and found increased in the absence of calcitonin for many cancer patients, specially with small cell lung tumors. The assay of HCG and its subunits with a great specificity and sensitivity is an other interesting example of the analytical power of Mabs. The usefulness of the assay of beta subunit is now clear in the diagnostic and follow up of choriocarcinoma and perhaps in the screening of high risk pregnancies. An other example can be derivated of our works on neuropeptide Y (NPY). The assay of NPY is highly difficult, due to its great similarity with other neuropeptides (PYY and PP). Mabs have been used to solve these analytical problems. The assay of NPY is useful not only for patients with neuroendocrine tumors, but also experimentally in the rat hypothalamus for research in nutrition.

Over the last few years, many tumor markers have been proposed to clinicians but only a limited number of them meet the necessary criteria to be useful for either screening, diagnosis, prognosis or follow-up of gastrointestinal (GI) tumors. Both CEA and Ca 19-9 have proven to be clinically useful for the detection of recurrent tumors. AFP remains the most useful marker for the follow-up of hepatocellular carcinoma (HCC). Its interest for the early detection of primary tumor is debated. Recent data suggest that assays based on monoclonal antibodies to AFP could be used for detection HCC in high risk populations. Decarboxy-prothrombin assay may be a complement to the AFP test in this localization. In addition to GI hormones, serotonin and urinary 5HIAA, Neuron Specific Enolase appears to be a valuable marker for the follow-up of neuroendocrine tumors of the GI tract. Only a few of the new tumor-associated antigens detected by monoclonal antibodies, appear to be promising clinical ly e.g. Ca50 TAG-72, PAO. Monoclonal antibodies to tumor-associated markers have also been used with other techniques: Immunohistochemistry: this technique is useful to the pathologist for the diagnosis of undifferentiated tumors by demonstrating the presence of specific antigens on tissue samples. Immunoscintigraphy: it can be useful for the detection of either metastases of recurrences of colorectal cancer by using anti-ACE antibodies labeled with Iodine 131 iodine 123 or indium 111. However immunoscintigraphy is less sensitive than both ultrasonography and CT scan for localizing hepatic metastases. At the present time the best indication of this method remains the diagnosis of pelvic recurrences.(ABSTRACT TRUNCATED AT 250 WORDS)