Sex Steroid Biosynthesis Enzymes in Ovarian Sex-Cord Stromal Tumors

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Abstract
Previous studies on neoplastic and hyperplastic ovarian lesions using paraffin-embedded material have demonstrated immunolocalization of sex steroid biosynthetic enzymes (SSBEs): P-450 side chain cleavage (P-450 SCC), which converts cholesterol to pregnenolone; 3 0-hydroxysteroid dehydroge- nase (3β-HSD), which converts pregnenolone to progesterone; P-450 17 α-hy- droxylase and lyase (P-450 17A), which convert progesterone to 17 α-hyrox- yprogesterone and 4-androstene-3,17-dione; and P-450 aromatase (P-450 AR), which converts 4-androstene-3,17-dione to estradiol. To investigate the utility of immunohistochemical staining for SSBEs, we studied a series of 45 sex cord-stromal tumors of the ovary. P-450 SCC was present in 9 of 11 Sertoli- stromal cell tumors, 3 of 12 granulosa cell tumors, 2 of 7 thecomas, and 1 of 1 stromal luteomas; 3β-HSD was present in 5 of 11 Sertoli-stromal cell tumors, 2 of 12 granulosa cell tumors, 2 of 7 thecomas, and 1 of 1 stromal luteoma; P-450 17A was present in 5 of 11 Sertoli-stromal cell tumors, 2 of 12 granulosa cell tumors, 2 of 6 thecomas, and 1 of 1 stromal luteomas; P-450 AR was present in 6 of 11 Sertoli-stromal cell tumors, 2 of 12 granulosa cell tumors, none of 7 thecomas, and 1 of 1 stromal luteoma. SSBEs were not present in 12 fibromas, one sclerosing stromal tumor, and one myxoma. Five of 45 patients with sex cord-stromal tumors showed androgenic effects; 4 of 11 patients with Sertoli-stromal cell tumors and the patient with a stromal luteoma. These five sex cord-stromal tumors contained P-450 SCC, and three of four of the Sertoli- stromal cell tumors contained 3β-HSD, P-450 17A, and P-450 AR. Concurrent endometrial histology was available in 25 of 45 sex cord-stromal tumor patients. None of the five sex cord-stromal tumors arising in patients with endometria that showed hyperplasia or adenocarcinoma showed immunoreactiv- ity for SSBEs. Eight patients' endometria were unremarkable, but their sex cord-stromal tumor contained SSBEs. SSBEs were present in areas showing Leydig cell, Sertoli cell, or steroid cell differentiation or luteinized areas; however, the results did not significantly add to the histologic classification of sex-cord stromal tumors. Androgenic hormonal effects could always be explained by synthesis of hormones by SSBEs present in the patient's sex cord- stromal tumor. Estrogenic hormonal effects, as measured by endometrial histologic findings, could rarely be explained by the synthesis of hormones by SSBEs present in the patient's sex cord stromal tumor. The estrogenic effect in these cases may be due to production of hormones by the adjacent ovarian stroma or in extraovarian sites. Removal of a sex cord-stromal tumor may not be complete hormonal treatment for a hyperplastic endometrium, as this tumor might not be the source for the hormones creating the problem in every case.

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