Prognostic relevance of hMLH1, hMSH2, and BAX protein expression in endometrial carcinoma

Endometrial carcinoma is the most common gynecologic malignancy in perimeno pausal and postmenopausal women. A role of mismatch repair genes, like hMLH 1 and hMSH2 in their pathogenesis, has been suggested. Loss of their functi on leads to the accumulation of replication errors (mutator phenotype), whi ch are responsible for further mutations in genes with microsatellite seque nces in their coding region, such as Bax. We analyzed the expression of hML H1, hMSH2, and Bax genes in 89 formalin-fixed paraffin-embedded endometrial carcinomas. The immunostains were scored with regard to percentage of posi tive tumor cells (0%, < 10%, 10 to 50%, > 50%), and relative staining inten sity (1+, 2+, 3+). The staining results were correlated with clinicopatholo gic features and survival. Loss of hMSH2 expression (0% positive cells) was observed in 1.1% (1/89) of the tumors; loss of hMLH1 was seen in 12.4% (11 /89) of the cases, particularly in endometrioid tumors with mucinous differ entation (5/11; 45%; P = .03). No significant association was found between the immunoscores and grade, stage criteria of the International Federation of Obstetrics and Gynecology (FIGO), or age of the patients. Among 11 tumo rs with loss of Bax expression (12.4%), 4 had also loss of hMLH1 (4/11; 36. 4%; P = .017). In multivariate analysis (Cox model), significantly longer s urvival was found for patients with tumors in FIGO Stage I-II (P < .0001), endometrioid type (P = .001), low grade (P = .001), and absence of hMLH1 ex pression (P = .027). Our results suggest that loss of function of hMLH1 and Bax occur in a subgroup of endometrial carcinoma. In addition to the class ical prognostic factors, absence of hMLH1 expression is associated with bet ter outcome of patients.