GATA-3 expression in trophoblastic tissues: an immunohistochemical study of 445 cases, including diagnostic utility

Abstract

Immunohistochemical expression of GATA-3 is seen predominantly in non-neoplastic bladder and breast epithelium and their respective carcinomas; however, data on expression in normal and lesional trophoblastic tissues are limited. Immunohistochemical staining for GATA-3 was assessed in a range of normal/lesional trophoblastic tissues and tumors in the differential diagnosis (n=445), including nonmolar products of conceptions/second and third trimester placentas/ectopic pregnancies, hydatidiform moles, placental site nodules, normal/exaggerated implantation sites, choriocarcinomas, epithelioid trophoblastic tumors, placental site trophoblastic tumors, atypical smooth muscle tumors (including leiomyosarcoma), and cervical and pulmonary squamous cell carcinomas. The extent of expression (0 to 4+) and intensity (weak to strong) were recorded. All cases with developing trophoblast/non-neoplastic trophoblastic proliferation and 81% of trophoblastic neoplasms were positive. Of all non-neoplastic trophoblast cell types, expression was observed in cytotrophoblast in 89% of cases, syncytiotrophoblast in 50%, intermediate trophoblast in 100%, and villous trophoblastic columns in 100%. Increasing gestational age was associated with a decrease in extent/intensity of expression in non-neoplastic cytotrophoblast and syncytiotrophoblast, whereas intermediate trophoblast maintained diffuse and strong expression from early to late gestation (P<0.0001). Eighty-nine percent of normal/exaggerated implantation sites showed 3+ or 4+ expression, whereas staining in 55% of placental site nodules was 1+ or 2+. Staining for GATA-3 was present in 78% of choriocarcinomas, 95% of epithelioid trophoblastic tumors, and 71% of placental site trophoblastic tumors. Although the number of choriocarcinomas and placental site trophoblastic tumors that showed a spectrum of expression ranging from negative to diffuse was relatively evenly distributed, 81% of epithelioid trophoblastic tumors had 3+ or 4+ staining. None of the atypical smooth muscle tumors and 3% of squamous cell carcinomas were positive, all of which exhibited weak staining. We conclude that GATA-3 is frequently expressed in normal and lesional trophoblastic tissues. It is also differentially expressed in intermediate trophoblast and cytotrophoblast/syncytiotrophoblast, which varies according to time during pregnancy. This study expands the spectrum of neoplasms known to express GATA-3. Thus, recognition of expression in trophoblastic tumors is important, because it can present a diagnostic pitfall in the assessment of suspected metastatic bladder or breast carcinomas involving the gynecologic tract. In the evaluation of diagnostically problematic tumors for which trophoblastic neoplasms are in the differential diagnosis, such as leiomyosarcoma and squamous cell carcinoma, GATA-3 can be included as part of an immunohistochemical panel particularly when other trophoblastic markers are either not available or yield ambiguous results.

Figure 1

Ectopic pregnancy, 1st trimester (A, H&E; B, GATA-3)- The cytotrophoblast and villous trophoblastic columns show diffuse strong expression. The syncytiotrophoblast are negative. Complete hydatidiform mole, 1st trimester (C, H&E; D, GATA-3)- Diffuse strong staining is present within villous trophoblastic hyperplasia and villous trophoblastic columns. 2nd trimester placenta (E, H&E; F, GATA-3)- GATA-3 is diffusely expressed with moderate-strong intensity in the intermediate trophoblastic island, but staining in the cytotrophoblast is substantially decreased in extent and intensity. The syncytiotrophoblast are largely negative. Fetal membranes, 3rd trimester (G, H&E; H, GATA-3)- The chorionic-type intermediate trophoblast are diffusely positive with strong intensity while the amnionic epithelium is negative.

Figure 2

Exaggerated implantation site (A, H&E; B, GATA-3)- Diffuse strong expression within implantation-type intermediate trophoblast. Multinucleated intermediate trophoblastic cells are also positive. Placental site nodule (C, H&E; D, GATA-3)- The chorionic-type intermediate trophoblastic cells show diffuse strong staining.

Figure 3

Choriocarcinoma (A, H&E; B, GATA-3)- The monophasic component shows diffuse weak-moderate staining; however, the syncytiotrophoblastic component is mostly negative. Epithelioid trophoblastic tumor (C, H&E; D, GATA-3)- GATA-3 is diffusely positive with moderate-strong intensity in the neoplastic chorionic-type intermediate trophoblastic cells.