PROGNOSTIC VALUE OF P53 AND K-RAS-2 TOPOGRAPHIC GENOTYPING IN ENDOMETRIAL CARCINOMA - A CLINICOPATHOLOGICAL AND MOLECULAR COMPARISON

The predictive value of p53 and K-ras-2 mutational genotyping in deter mining tumor aggressiveness and survival in patients with endometrial carcinoma (EC) was retrospectively evaluated using a molecular genotyp ing approach on fixative treated tissue specimens. Two groups of patie nts with EC were selected based upon length of survival. Group A consi sted of 14 patients that died within 3 years of initial diagnosis and treatment (mean survival of 1.1 years). Group B consisted of 18 patien ts that survived beyond 3 years (mean survival of 4.7 years). Clinicop athologic features including clinical stage, histologic type, and comb ined nuclear and architectural grade of each tumor were statistically analyzed with respect to oncogene/tumor suppressor gene alterations, T he majority of carcinomas in group A were serous (57%), stage III or I V (93%), and high combined grade (938). Group B consisted mostly of en dometrioid (89%) and low-grade carcinomas (83%); 56.1% were stage III or IV. K-ras-2 point alterations were found in 2 (14%) and 4 (22%) pat ients from group A and B respectively; the spectrum of K-ras-2 genotyp es was similar in both groups. p53 gene mutations were identified in 9 (64%) and 1 (6%) patient from group A and B respectively. p53 stainin g in group A tended to be of strong intensity and diffuse distribution , being associated with the presence of point mutations, mainly in exo n 8. Only a single group B tumor exhibited point mutational change. Th e presence of p53 mutations strongly correlated with short survival (p <0.05) but the finding of K-fas-2 alterations did not. p53 genotyping has potential prognostic value in EC and can be used along with histo pathologic type and histologic grade to identify subsets of more aggre ssive tumors and to guide the treatment.