Comparative immunohistochemical analysis of granulosa and sertoli components in ovarian sex cord-stromal tumors with mixed differentiation: potential implications for derivation of sertoli differentiation in ovarian tumors.

Granulosa cell tumors of the ovary occasionally show admixed Sertoli components, just as tumors that are predominantly Sertoli or Sertoli-Leydig cell tumors can contain minor granulosa elements. Although the immunoprofiles of pure granulosa cell tumors and pure Sertoli cell tumors have been characterized, little is known regarding what immunophenotypic relationships exist between the granulosa and Sertoli components in ovarian sex cord-stromal tumors that contain both elements. Furthermore, it is not completely understood why sex cord-stromal tumors of the ovary with female-type (granulosa) differentiation can produce male-type (Sertoli) differentiation. To better understand why simultaneous differentiation into female-type and male-type components occurs, eight tumors with mixed differentiation were stained with a panel of antibodies to androgen receptor (AR), calretinin, CD10, CD99, estrogen receptor, inhibin, Ki-67, low molecular weight cytokeratin, pancytokeratin, progesterone receptor, p53, and vimentin. Immunohistochemical composite scores were determined separately for the matched pairs of granulosa and Sertoli components in each case. Differences between both components were statistically analyzed using the Wilcoxon signed rank test. AR and vimentin expression showed a difference at the 10% statistical significance level (p < 0.1), demonstrating higher levels of expression in the granulosa components. The differences between the granulosa and Sertoli components in expression of CD99, inhibin, or pancytokeratin were not statistically significant (p > 0.1, each). Statistical calculations could not be made for calretinin, CD10, estrogen receptor, Ki-67, low molecular weight cytokeratin, progesterone receptor, or p53, although the overall mean levels of expression of CD10 and low molecular weight cytokeratin were substantially higher in the Sertoli components. Not surprisingly, the granulosa and Sertoli components of ovarian sex cord-stromal tumors with mixed differentiation show overlapping immunophenotypic profiles consistent with derivation from a common lineage rather than reflecting a composite tumor. However, because components of a sex cord-stromal tumor simultaneously differentiate along granulosa or Sertoli lines, they seem to show preferential expression of certain antigens. CD10 and low molecular weight cytokeratin are more often associated with Sertoli cell differentiation, whereas AR and vimentin expression seem to reflect granulosa differentiation.