Immunohistochemical detection of mutant P53 protein and human papillomavirus-related E6 protein in anal cancers.
OBJECTIVE
The wild-type P53 protein, a product of the P53 gene, is a normal growth controlling protein. Mutation of the P53 gene generates a mutant P53 protein which promotes tumor formation through loss of growth suppression. Some of the agents responsible for P53 gene mutation are known, one of which may be tumorigenic human papillomavirus (HPV) infection. Anal cancers are demonstrating a changing trend in the affected population, from older females in the older reported series to younger males more recently. This may be a reflection of infection with tumorigenic HPV types 16 and 18. The E6 oncoprotein of these viruses inactivates the growth-controlling wild-type P53 protein. In this study, our purpose was to determine the incidence of mutant P53 and HPV-16 and 18-related E6 protein and their coexpression in anal cancers.


METHODS
We examined 29 anal cancers immunohistochemically for mutant P53 protein, HPV 16 and 18 E6 protein, and coexpression of the two.


RESULTS
Mutant P53 protein was present in 58.6 percent of anal cancers overall and in 85.7 percent of anal adenocarcinomas. E6 oncoprotein was present in five cases (17.2 percent), all of which were squamous-cell carcinomas. Coexpression of both mutant P53 and E6 proteins was seen in only three cases (10.3 percent).


CONCLUSIONS
Although tumorigenic HPV may be an important cause for P53 gene mutation in anal cancers, perhaps other mutagenic factors play a predominant role.
Jakate
S M
SM
Department of Pathology, Rush Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612.
Saclarides
T J
TJ
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001005:Anus Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005819:Genetic Markers; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis*; D027383:Papillomaviridae; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; C052603:E6 protein, Human papillomavirus type 18; D005819:Genetic Markers; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53