P16 expression in anorectal carcinoma biopsy specimens seen in the department of pathology makerere university college of health sciences.

Abstract

BACKGROUND: There is an increasing number of cases of anorectal carcinoma in both men and women in Uganda and there is evidence in the role of hr-HPV in its pathogenesis. P16 has been shown in studies in developed countries such as U.S.A, Europe and Asia to be a useful surrogate biomarker in the identification of anorectal carcinoma harbouring hr-HPV DNA. It is presumed to be a molecular biomarker for malignant and premalignant high risk HPV- induced cervical and vulva lesions, squamous cell carcinoma of the anorectal region, penile carcinoma and oral lesions. P16 expression in both in situ and invasive cervical adenocarcinoma is recognised as a predictor of poor prognosis in these lesions. Recently, immunohistochemical expression of P16 has been used to discriminate cervical from endometrial adenocarcinomas if accompanied by high-risk HPV types. It has also been used as a adjunct for the evaluation of treatment response in HPV- associated malignancies and their precursor lesions. P16 expression in anorectal carcinoma in Ugandan patients is unknown. OBJECTIVE: The objective of the study was to determine the prevalence of P16 and describe its expression in anorectal carcinoma biopsy specimens in relation to age, gender, histological types and grades as seen in the department of pathology makerere university college of health sciences between 1997 and 2007. METHODOLOGY: This was a cross-sectional descriptive laboratory based study. A total of 111 paraffin embedded biopsy specimen seen in the department of pathology between 1997 and 2007 were studied. These specimens were assessed using H and E and then by employing tissue microarray technology were subjected to immunohistochemical methods using monoclonal antibody p16ink4A derived from mtm Laboratories Germay. EPIDATA was used for data entry and SPSS for analysis. Data was analyzed with respect to the variables. Data for gender, site for carcinoma, pattern of p16 expression, Histological grades and histological types were summarized into frequencies while the data for age was summarized into means. Data for the frequencies was presented in form of histograms and frequency tables. Photomicrographs were used to display H & E and P16 immunohistochemical staining. The assessment for the expression of P16 in relation to age, gender, histological types and grades was done using chi-square tests or t-test. Comparison of mean ages and mean positive cells was done using a t-test. RESULTS: Of the 111 biopsy specimens, 76 (68.5%) were p16 positive. The age ranged from 13-80 years with a mean age of 49.84 (SD 15.57). The mean age of the 76 p16 positive cases was 50.34 (SD 16.13) while that of the p16 negative cases was 48.74 (SD 14.44). There was 38 (70.4%) cases below 50 years and 38 (66.7%) cases of 50 years and above which were p16 positive. On the other hand, 32 (65.3%) males and 44 (71%) females were p16 positive. There were 12 (70.6%) cases of squamous cell carcinomas and 64 (68.1%) cases of adenocarcinomas which were p16 positive. On the other hand, 49 (71.0%) cases in grade one, 24 (72.7%) cases in grade two and 3 (33.3%) cases in grade three were p16 positive. CONCLUSION: The overall prevalence of p16 in anorectal carcinoma biopsy specimens seen at the department of pathology makerere university college of health sciences was 68.5%. The prevalence of p16 in squamous cell carcinoma was 70.6% while that in adenocarcinoma was 68.1%. There was no significant difference in the expression of p16 in anorectal carcinoma in relation to age, gender and histological types of anorectal carcinoma. There was a statistically significant difference in the expression of p16 in anorectal carcinoma in relation to the histological grades.