FATTY-ACID SYNTHASE EXPRESSION IN ENDOMETRIAL CARCINOMA - CORRELATIONWITH CELL-PROLIFERATION AND HORMONE RECEPTORS

BACKGROUND. Fatty acid synthase (FAS), a biosynthetic enzyme, normally functions in the Liver to convert dietary carbohydrate to fat, but it is minimally ex pressed in most other normal adult tissues. EAS is ex pressed at markedly elevated levels in subsets of human breast, ovaria n, and prostate carcinomas that are associated with poor prognoses. Du ring the menstrual cycle, the expression of FAS in the human endometri um is closely linked to the expression of the proliferation antigen Ki -67, estrogen receptor (ER), and progesterone receptor (PR). METHODS. This study reports the expression patterns of these antigens in 35 end ometrial carcinomas as determined by immunohistochemical analysis. RES ULTS, All cases demonstrated a close direct correlation between FAS an d Ki-67 expression. Average FAS expression levels were correlated with tumor grade. Twenty-five carcinomas that were positive for ER and PR showed close correlation in expression of FAS, Ki-67, and hormone rece ptors. Individual tumors displayed varying degrees of heterogeneity of expression. A few well-differentiated carcinomas showed very low expr ession of all four antigens, similar to the antigenic profile of secre tory endometrium. Nine high grade carcinomas that were negative for ER and PR also showed close correlation in expression of FAS and Ki-67 w ith uniformly high expression. CONCLUSIONS. These data suggest the fol lowing hypothesis: In hormone-dependent endometrial cells, FAS express ion is part of the estrogen-driven cellular response that leads to pro liferation; however, its linkage to proliferation is such that FAS exp ression is maintained in proliferating cells in endometrial carcinomas that acquire hormone independence. The use of these four antibodies a s a panel may increase the diagnostic utility of ER and PR immunohisto chemistry for tumor classification and prediction of the responsivenes s of tumors to hormonal therapy. Cancer 1998;83:528-37. (C) 1998 Ameri can Cancer Society.