The presence and distribution of increased expression of H-ras p21 protein, c-myc protein and p53 protein, or of human papillomavirus (HPV) DNA were investigated in 42 Japanese patients with esophageal squamous cell carcinoma (SCC) by immunohistochemical techniques using each protein antibody, and by in situ hybridization with fluorescein isothiocyanate (FITC)-labelled DNA. probes for HPV-16 and HPV-18. Eighteen cases were positive with H-ras p21 antibody, but only one with c-myc protein antibody. Positive reaction of the cancer cell nuclei with p53 antibody was found in 14 cases. Among these positive cases with H-ras p21 or p53 antibody, 7 were double positive. In addition, we found positive results in 7 cases with HPV-16, and 8 cases with HPV-18, including 2 double positive cases. Among them, 6 cases were also positive with H-ras p21. Only HPV infection or p53 overexpression was detected each in 7 cases. All of HPV-positive tumors were negative with p53 antibody. Moreover, among the cases with the expression of I-I-ins p21, combined cases with overexpressed p53 protein or HPV infection counted for more than 50%. Statistically, these combined cases showed worse survival rate than only H-ras p21 positive ones. Judging from these results obtained in the present study, the increased expression of H-ras p21 protein as well as p53 and/or HPV may be involved in the carcinogenesis of this kind of disease, and become apparent, when the function of p53 as a tumor suppressor gene is inhibited with overexpressed p53 protein or HPV oncoprotein, resulting in a poor prognostic indicator.

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