Mutation and overexpression of p53 as a prognostic factor in canine mammary tumors.
We concentrated ourselves to evaluate the prognostic significance of the p53 gene mutations, its protein expression and MIB-1 index as a proliferative marker in canine mammary tumors. In the present study, a total of 20 cases were examined, among which there were 5 malignant mixed tumors, 4 mammary gland adenocarcinomas, 1 papillary adenocarcinoma, 8 benign mixed tumors and 2 mammary gland adenomas. Positive immunostaining for p53 with PAb240 antibody was found in 2 benign (20%) and 3 malignant (30%) tumors. However, PAb421 antibody did not give positive result at all. In Western blot analysis, the p53 expression in benign and malignant tumors was detected in 4 and 3 cases, respectively. p53 mutations were found in 6 cases out of the cases with detected p53 protein expression. The MIB-1 index in benign and malignant tumors were 17.6+/-20.8% and 29.0+/-27.2%, respectively and there was no significant difference between tumor types. There was a significant correlation between p53 mutations and p53 overexpression (correlation coefficient = 0.5, p < 0.05). In Kaplan-Meier survival analysis, the p53 index was associated with significantly shortened survival time (p < 0.01). In multivariate analysis, p53 overexpression was only an independent factor for indicator of worse prognosis in canine mammary tumors (p = 0.01). These results demonstrated that p53 gene mutations and protein overexpression using the PAb240 anti-p53 antibody were useful predictors of increased malignant potential and poor prognosis in canine mammary tumors.
Lee
Chung-Ho
CH
Department of Veterinary Surgery, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Korea. ohkweon@snu.ac.kr
Kim
Wan-Hee
WH
Lim
Ji-Hey
JH
Kang
Min-Soo
MS
Kim
Dae-Yong
DY
Kweon
Oh-Kyeong
OK
D000818:Animals; D000974:Antibodies, Antinuclear / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015153:Blotting, Western / Q000662:veterinary; D004283:Dog Diseases / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D007150:Immunohistochemistry / Q000662:veterinary; D019394:Ki-67 Antigen / Q000378:metabolism; D015674:Mammary Neoplasms, Animal / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D019394:Ki-67 Antigen; C440408:MIB-1 antibody; D016159:Tumor Suppressor Protein p53