Background: Cervical carcinomas are second most frequent type of women cancer. Success in diagnostics of this disease is due to the use of Pap-test (cytological smear analysis). However Pap-test gives significant portion of both false-positive and false-negative conclusions. Amendments of the diagnostic procedure are desirable. Aetiological role of papillomaviruses in cervical cancer is established while the role of cellular gene alterations in the course of tumor progression is less clear. Several research groups including us have recently named the protein p16 INK4a as a possible diagnostic marker of cervical cancer. To evaluate whether the specificity of p16 INK4a expression in dysplastic and neoplastic cervical epithelium is sufficient for such application we undertook a broader immunochistochemical registration of this protein with a highly p16 INK4a -specific monoclonal antibody.
Medical histories of 101 urothelial bladder cancer patients were compared with the results of morphological analysis and biomolecular detection of human papilloma viruses (HPV) in the tumor specimens. DNA of HPV16 (the major type of virus responsible for appearance of cervical carcinoma) was detected in 38 specimens, while mRNA of E6 and E7 oncogenes and E7 oncoprotein of HPV16 were observed in 13 specimens. HPV-positive bladder cancer was characterized by higher degree of cell anaplasia than HPV-negative cancer; in the primary bladder tumor, HPV was detected more often than in recurrent bladder cancer. These data attest to involvement of HPV16 in the genesis of bladder cancer. No correlations of HPV status of bladder tumor with patient's sex, age, and invasion into the muscle layer were revealed.
A battery of tests for detection human papillomavirus DNA, mRNA corresponding to viral oncogenes, and viral oncoprotein E7 in cancer bladder urothelium was piloted in 35 samples of bladder cancer. DNA of human papillomavirus type 16 (causes cervical cancer) was found in 16 (46%) samples; E6/E7 oncogene transcript and E7 oncoprotein of human papillomavirus type 16 were detected in 10 and 7 human papillomavirus DNA-positive samples, respectively. These findings attest to association of bladder cancer with human papillomavirus in Russia.
Hyperexpression of p16(INK4a) protein is an early marker of cervical cancer. Hyperexpression of INK4a gene encoding this protein at the level of mRNA and p16(INK4a) was detected in tumor cells of some patients with bladder cancer associated with human papilloma virus-16. However, in contrast to cervical cancer, this phenomenon in urothelial carcinomas does not correlate with expression of human papilloma virus-16 oncogenes E6 and E7.
Lynch syndrome is the most common cancer-prone syndrome associated with a high risk of colorectal cancer (CRC), neoplasms of the upper gastrointestinal system, the urinary tract, the female reproductive system, brain tumours and others. The only known form of hereditary endometrial cancer is also diagnosed as part of Lynch syndrome. One or more pathogenic germline mutations in one of the mismatch repair (MMR) genes are the cause of Lynch syndrome. Mapping of MMR genes and the discovery of microsatellite instability (MSI) have given rise to the possibility of using these clue characteristics of the pathogenic process for the elaboration of a screening test for Lynch syndrome. Being highly accurate and superior to all previously developed clinical criteria and guidelines, MSI-testing along with the assessment of the expression patterns of MMR proteins by immunohistochemistry has taken the leading role in the early diagnosis of Lynch syndrome. This article focuses on a brief review about the main evolutionary stages of clinical, anamnestic, molecular and genetic criteria for Lynch syndrome together with the results of our own research on the accuracy of the Amsterdam criteria, the Bethesda guidelines and MSI-diagnostics in the determination of the indications for MMR-genotyping in colorectal cancer patients suspected for Lynch syndrome.
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