EXPRESSION OF EPIDERMAL GROWTH-FACTOR FAMILY PROTEINS AND EPIDERMAL GROWTH-FACTOR RECEPTOR IN HUMAN ENDOMETRIUM

The biological significance of epidermal growth factor (EGF)related pr oteins in the development and progression of endometrioid endometrial carcinoma was studied. Expression of EGF-related proteins including EG F, transforming growth factor-alpha (TGF-alpha), cripto (CR), amphireg ulin (AR), and EGF receptor (ECFR) were immunohistochemically examined . Results were then correlated with clinicopathologic findings and ste roid receptor status in 12 specimens with normal endometrium, 13 with endometrial hyperplasia, and 40 with endometrioid endometrial carcinom a. EGFR, EGF, TGF-alpha, and CR immunoreactivities were observed in 58 .3%, 66.7%, 91.6%, and 66.7% of normal endometrial specimens; 100%, 15 .4%, 100%, and 30.8% of endometrial hyperplasia specimens; and 67.5%, 32.5%, 65.0%, and 65.0% of endometrial carcinoma specimens, respective ly. AR immunoreactivity was not observed in any of the normal, hyperpl astic, or neoplastic endometrium. The presence or absence of EGFR or T GF-alpha in endometrial carcinoma correlated with surgical stage, dept h of myometrial invasion, and findings from peritoneal washing cytolog y. EGF expression significantly correlated with the age of the patient s and that of CR with surgical stage and peritoneal washing cytologica l findings. There was a significant correlation between EGFR and TGF-a lpha expression, and between EGF and TGF-alpha. Coexpression of EGFR a nd TGF alpha, EGFR and CR, and TGF-alpha and CR in carcinoma specimens significantly correlated with advanced surgical stage, deeper myometr ial invasion, and positive peritoneal washing cytology. In normal as w ell as hyperplastic endometrium, endometrial glands immunohistochemica lly positive for TGF-alpha were generally positive for ER, but in poor ly differentiated endometrial carcinoma, cells positive for TGF-alpha tended to be negative for ER. The results of the present study show th at among EGF-related proteins, expression of TGF-alpha and CR seem to be associated with the progression of human endometrioid endometrial c arcinoma. Additionally, expression of TGF-alpha became increasingly es trogen independent with increasing histological carcinoma grades. (C) 1996 by W.B. Saunders Company