Diagnostic Utility of Hepatocyte Nuclear Factor 1-Beta Immunoreactivity in Endometrial Carcinomas: Lack of Specificity For Endometrial Clear Cell Carcinoma

Hepatocyte nuclear factor 1-beta (HNF1 beta) has recently emerged as a relatively sensitive and specific marker for ovarian clear cell carcinoma. The purpose of this study is to assess the diagnostic utility of this marker for endometrial clear cell carcinoma. Immunohistochemical analysis was performed on 75 endometrial tissues using a goat polyclonal antibody raised against a peptide mapping at the C-terminus of human HNF1 beta protein. The 75 cases included 15 clear cell carcinomas, 20 endometrioid carcinomas, 15 endometrial serous carcinomas/uterine papillary serous carcinomas, 20 cases of normal endometrium, 2 cases of clear cell metaplasia, and 3 cases of Arias Stella reaction. Staining interpretations were based on a semiquantitative scoring system, a 0 to 12+ continuous numerical scale that was derived by multiplying the extent of staining (0 to 4 + scale) by the intensity of staining (0 to 3 + scale) for each case. HNF1 beta expression was found to be present in a wide spectrum of tissues. Twenty-seven (54%) of the 50 carcinomas displayed at least focal nuclear HNF1 beta expression, including 11 (73%) of 15,9 (60%) of 15, and 7 (35%) of 20 clear cell, serous, and endometrioid carcinomas, respectively. The average nuclear staining scores for clear cell carcinomas, endometrioid carcinomas, and serous carcinomas were 5.2, 1.4, and 4.1, respectively. Clear cell carcinomas and endometrioid carcinomas displayed statistically significant differences regarding their nuclear staining scores (P = 0.0027), but clear cell carcinomas and endometrial serous carcinomas did not (P = 0.45). The calculated sensitivity of any nuclear HNF1 beta expression in classifying a carcinoma as being of the clear cell histotype was 73%, whereas the specificity was 54%. Nineteen of 20 normal endometrium samples displayed at least focal nuclear expression of HNF1 beta, and this expression was often diffuse. The 5 cases of benign histologic mimics of clear cell carcinomas (Arias Stella reaction and clear cell metaplasia) displayed some degree of HNF1 beta immunoreactivity, with an average nuclear staining score of 7.3. We conclude that although HNF1 beta is frequently expressed in clear cell carcinomas, it should be used with caution as a diagnostic marker because of its lack of specificity. It neither distinguishes endometrial serous carcinomas from clear cell carcinomas nor clear cell carcinomas from its benign mimics. The greatest diagnostic utility of HNF1 beta expression may be in a supportive evidentiary role favoring clear cell carcinoma when the principal differential diagnostic consideration is endometrioid carcinoma.