IMMUNOHISTOCHEMICAL DETECTION OF P53 TUMOR-SUPPRESSOR GENE PROTEIN INCANINE EPITHELIAL COLORECTAL TUMORS

Eighty canine epithelial colorectal tumors obtained by excisional biop sy were evaluated immunohistochemically for p53 tumor suppressor gene protein. Dogs in the study averaged 6.9 years of age (range, 1-12.5 ye ars). A standard avidin-biotin immunohistochemical protocol incorporat ed a polyclonal antibody of rabbit origin (CM-I) as the primary antibo dy. Positive staining was observed within all subcategories of lesions , including hyperplastic polyps 1/2 (50%), adenomas 14/29 (48%), carci nomas in situ 9/22 (41%), adenocarcinomas 3/4 (75%), and invasive carc inomas 8/23 (35%). A total of 35/80 (44%) positive tumors were identif ied. Fifteen of 31 (48%) benign tumors labeled for p53 protein compare d to 20/49 (41%) malignant tumors. Survival data was available for 57/ 80 (71%) dogs. The average age of dogs within the group with survival data was 4.4 years. Males predominated 34/57 (60%). Mean survival time was 20.6 months. There was no significant difference in survival time between dogs grouped according to p53 immunoreactivity, cellular stai n location, or tumor site. A statistically significant increase in sur vival time was observed between dogs with clean surgical margins and t hose without (P < 0.018) and for dogs with adenomas or carcinomas in s itu over dogs with invasive carcinomas (P < 0.02). In this study, the overall greater positive staining frequency of benign lesions compared to malignant lesions is contrary to data derived from similar immunoh istochemical analyses of human tumors and is incongruous with the theo rized late-stage participation of the p53 protein in the development o f human colorectal cancers. The results of this study suggest that if the p53 tumor suppressor gene protein is involved in the progression o f canine colorectal tumors, it may play a relatively early role, possi bly analogous to the early appearance of p53 overexpression in precanc erous lesions of human ulcerative colitis. Immunohistochemical detecti on of p53 was not useful prognostically.