INTERRELATIONSHIP BETWEEN THE EXPRESSION OF H-RAS P21, C-MYC AND P53 PROTEINS, AND THE INFECTION OF HIGH-RISK HUMAN PAPILLOMAVIRUSES IN JAPANESE PATIENTS WITH ESOPHAGEAL SQUAMOUS-CELL CARCINOMA

The presence and distribution of increased expression of H-ras p21 pro tein, 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 pro tein antibody, and by in situ hybridization with fluorescein isothiocy anate (FITC)-labelled DNA. probes for HPV-16 and HPV-18. Eighteen case s were positive with H-ras p21 antibody, but only one with c-myc prote in antibody. Positive reaction of the cancer cell nuclei with p53 anti body was found in 14 cases. Among these positive cases with H-ras p21 or p53 antibody, 7 were double positive. In addition, we found positiv e 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 mor e than 50%. Statistically, these combined cases showed worse survival rate than only H-ras p21 positive ones. Judging from these results obt ained in the present study, the increased expression of H-ras p21 prot ein 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 a s a tumor suppressor gene is inhibited with overexpressed p53 protein or HPV oncoprotein, resulting in a poor prognostic indicator.