GATA3 Expression in Common Gynecologic Carcinomas: A Potential Pitfall

Abstract

GATA binding protein 3 (GATA3) immunohistochemistry is primarily used as a marker of breast and urothelial differentiation, particularly in metastatic settings. In the gynecologic tract it also serves a robust marker for mesonephric and trophoblastic tumors. However, expression has also been described in more common malignancies of gynecologic tract including ovarian, endometrial, and cervical carcinomas. Data on the distribution of GATA3 expression in gynecologic malignancies is somewhat limited, particularly across different histologic subtypes of ovarian, endometrial, and cervical carcinomas. To assess the rates of GATA3 expression among common gynecologic cancers of various histologic types, 100 ovarian carcinomas, 64 endometrial carcinomas/atypical hyperplasias, 16 cervical squamous cell carcinomas (SCCs), and 14 endocervical adenocarcinomas were evaluated by immunohistochemistry for GATA3 positivity. Eight percent of endometrial carcinomas expressed GATA3, including 2 serous carcinomas, 1 carcinosarcoma, and 1 case of atypical hyperplasia. Six percent of ovarian carcinomas were GATA3-positive including 2 clear cell carcinomas, 2 mucinous adenocarcinomas, and 2 high-grade serous carcinomas. Thirty-eight percent of cervical SCCs showed weak to moderate staining in up to 50% of tumor cells. All endocervical adenocarcinomas were entirely negative for GATA3. In summary, GATA3 shows focal weak to moderate expression in a subset of endometrial and ovarian carcinomas. In contrast, usual-type endocervical adenocarcinomas are typically negative for GATA3, which can be helpful in differentiating them from mesonephric proliferations or carcinomas. A larger proportion of cervical SCCs express GATA3, therefore caution should be exercised when using this stain in the setting of a lower genitourinary carcinomas.

High-Grade Endometrioid Carcinoma of the Endometrium With a GATA-3-Positive/PAX8-Negative Immunophenotype Metastatic to the Breast: A Potential Diagnostic Pitfall

“…GATA-3 was originally identified as an organspecific biomarker for breast and urothelial differentiation, but with commonly less frequent expression, it has been identified in several other carcinomas including endometrial carcinoma. [2][3][4][5][6][7][8][9][10] Thus, its expression could be a potential pitfall when making a pathologic diagnosis and should be interpreted in an appropriate clinicopathological context. In our case, GATA-3 nuclear expression was weakly identified in <50% of the cells in a metastatic breast lesion.…”

“…In our review of the literature, GATA-3 expression in endometrial carcinomas ranged in frequency from 0% to 13%. 7,10 Studies quantifying GATA-3 expression in endometrial lesions are summarized in Table 1. [3][4][5][6][7][8][9][10] GATA-3 expression in endometrial lesions was reported as being of weak to moderate intensity in the majority of cases in all studies, with a single exception.…”

“…7,10 Studies quantifying GATA-3 expression in endometrial lesions are summarized in Table 1. [3][4][5][6][7][8][9][10] GATA-3 expression in endometrial lesions was reported as being of weak to moderate intensity in the majority of cases in all studies, with a single exception. 2,[7][8][9][10] For endometrioid endometrial carcinomas, GATA-3 expression range in frequency from 2% to 10%, with more frequent expression in high-grade endometrioid carcinoma.…”

“…2,[7][8][9][10] For endometrioid endometrial carcinomas, GATA-3 expression range in frequency from 2% to 10%, with more frequent expression in high-grade endometrioid carcinoma. 10 Furthermore, GATA3 expression may be of prognostic significance in high-grade endometrial tumors. 13 In one study, GATA-3 expression was found in 19% (40 of 209 cases) of endometrioid carcinomas and 57% (12 of 21 cases) of serous papillary/clear cell carcinoma.…”

“…Notably, GATA-3 expression has been identified in endometrial carcinoma, albeit at a much lower frequency than has been observed in breast and urothelial carcinomas. 2,[7][8][9][10] Accordingly, GATA-3 expression can be a diagnostic pitfall when the clinical differential diagnosis for a tumor is between a breast and gynecologic origin. Similarly, PAX-8 is a biomarker that is expressed in a high proportion of most but not all gynecologic tract carcinomas.…”