engleski

Immunohistochemical Profiling of Proteins involved in HPV induced Uterine Cervix Carcinogenesis: A Tissue Microarray Study

The involvement of human papillomavirus (HPV) in the development of carcinoma of the uterine cervix has been firmly established. However, other genetic alterations play an important role in pathogenesis of cervical cancer. The aim of this study was to analyse the immunohistochemical protein expression patterns of epidermal growth factor receptor (EGFR), p53, p16 (INK4A) and Ki 67 in cervical carcinoma using tissue microarray technology. Methods: The expression of EGFR, p53, p16 and Ki67 was studied in series of 34 cervical cancer samples: 14 squamous cell carcinomas (SCC), 6 cervical intraepithelial neoplasia (CIN III), and 14 adenocarcinomas, (ADC). The protein analysis was performed on routine formalin-fixed, paraffin-embedded tissue materials with immunohistochemical staining of the samples, assembled on a tissue microarray, in duplicate. Results: High-risk HPV-DNA was identified in 94 % (32/34) of the cases. HPV-16 predominated in SCC and CIN III, while HPV 18 and HPV 16/18 mixed infection were detected in ADC. Ninety-one percent (31/34) of uterine cervix neoplasia exhibited strong proliferative activity (+2 and +3 Ki 67 immunopositivity), while expression of p16, p53 and EGFR were recorded in 64% (22/34), 73% (25/34) and 61 % (21/34) neoplasia, respectively. According to the histological type, SCC and ADC demonstrated high expression of Ki67, p16 and p53, while in CIN III only high expression was detected for Ki67. Both p16 and p53 demonstrated low protein expression in CIN III. Substantial differences were shown in EGFR expression: SCC and CIN III demonstrated high level of EGFR expression, 92 % (13/14) and 100% (6/6), respectively. In eighty-five percent of ADC’s the expression of EGFR was absent (9/14) or (+1) intensity (3/14). Only two tumors demonstrated moderate/strong (+2) level of expression. Conclusion: In this preliminary study we have confirmed the reliability of tissue microarray technology in protein expression studies. It is also necessary to continue the investigation of EGFR expression in ADC and adenosquamous carcinoma to elucidate the role of EGFR expression in these histological types of uterine cervix carcinomas.

cervical cancer; HPV; EGFR; p16; Ki 67; tissue microarray

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