Immunohistochemical markers as a diagnostic aid in ovarian pathology

With the advent of new antibodies and the discovery of novel applications of established markers, immunohistochemistry is increasingly being used in gynaecological pathology. Most of the applications in the field of ovarian pathology are related to the diagnosis of neoplasia; as yet, there are few situations where immunohistochemistry has proven useful in a prognostic or predictive sense.Immunohistochemistry is useful in distinguishing between a primary ovarian adenocarcinoma of endometrioid or mucinous type and a metastatic neoplasm from the colorectum, although it is stressed that many ovarian mucinous tumours express enteric markers, at least focally. In this distinction, a panel comprising CK7, CK20, CA125, CEA, ER and CDX2 is recommended. Markers may also be of value in distinguishing a primary ovarian adenocarcinoma from a metastasis from other sites but it is stressed that there is significant overlap in immunophenotype between pancreatic, biliary and gastric adenocarcinomas and primary ovarian mucinous carcinomas, a situation where there is not infrequently diagnostic confusion. The various markers discussed may also be of value in peritoneal biopsy or fluid specimens when faced with an adenocarcinoma of unknown primary.Immunohistochemistry is also useful in diagnosing other ovarian metastatic tumours, e.g. malignant melanoma, where the histological features may not be typical and the diagnosis not considered, especially in the absence of a known primary elsewhere. WT1 is useful in typing a primary ovarian carcinoma as most ovarian (and tubal and peritoneal) serous adenocarcinomas exhibit diffuse nuclear positivity while the other common types are typically negative, as is uterine serous carcinoma. As such, diffuse nuclear WT1 immunoreactivity in a disseminated serous carcinoma suggests an ovarian, peritoneal or tubal rather than a uterine origin. There are several useful markers of ovarian sex cord-stromal tumours, especially inhibin and calretinin, but also melan A and CD99. CD56 has recently been shown to be an extremely sensitive marker of ovarian sex cord-stromal tumours, although it lacks specificity. Immunohistochemistry may contribute to diagnosis in the broad fields of undifferentiated, spindle cell and small cell ovarian neoplasms; nuclear WT1 immunoreactivity is common in ovarian small cell carcinoma of hypercalcaemic type.Other areas where immunohistochemistry may contribute include the categories of neuroendocrine tumours and thyroid tissue (struma ovarii) with an unusual morphological appearance, including oxyphil or clear cells, such that thyroid tissue may not immediately spring to mind. There are several useful markers of malignant germ cell tumours, including established antibodies such as α-fetoprotein and placental alkaline phosphatase and relatively new markers, such as OCT4, which is positive in dysgerminoma and embryonal carcinoma.Throughout this review it is stressed that careful morphological examination, combined with consideration of the clinical and gross pathological features and judicious sampling, remains the mainstay in diagnosis. In problematic cases, a panel of markers should be carefully chosen based on the differential diagnoses under consideration; in this author’s experience, an inappropriate panel of markers is often chosen seemingly with little focus. It is stressed that unexpected staining may be encountered, one example being the recent discovery that TTF1, a hitherto considered reliable marker of thyroid and pulmonary neoplasms, is not uncommonly expressed in ovarian and other gynaecological adenocarcinomas.