Expression of sonic hedgehog signaling molecules in normal, hyperplastic and carcinomatous endometrium

The aim of the present study was to determine the expression profile of the hedgehog (Hh) signaling molecules in normal, hyperplastic, and carcinomatous uterine endometrium. For this purpose, 271 endometrial tissue samples, (62 of normal endometrium, 127 of endometrial hyperplasias, and 82 endometrial adenocarcinomas) were studied using antibodies recognizing Hh-related signaling proteins, such as, sonic hedgehog (Shh), Patched (PTCH), Smoothened (Smo), Suppressor of fused [Su(Fu)], Gli-1, Gli-2, and Gli-3 by immunohistochemistry. The mRNA expression of these molecules was also assessed on reverse transcription-polymerase chain reaction. In the normal endometrium, the expression of Hh signaling molecules was generally downregulated except for Su(Fu), Gli-2, and Shh. In particular, the expression of both PTCH and Smo was very low or almost absent. Overall expression of Hh signaling molecules increased in hyperplastic endometrium; in particular, PTCH and Smo were significantly highly expressed in complex and atypical hyperplasia. In carcinoma samples extensive alterations were observed in the expression pattern of the signaling molecules. Nuclear Gli-2, cytoplasmic Gli-3, and Su(Fu) were overexpressed, whereas Shh, PTCH, and Smo expression were significantly reduced compared with the hyperplastic endometrium. The results suggest that the alteration of Hh signaling may be implicated in tumorigenesis of the endometrium.