Pax8: A marker for carcinoma of Müllerian origin in serous effusions

Abstract

PAX8 is a nuclear transcription factor with limited expression in normal and neoplastic tissues in a cell lineage-dependent manner. PAX8 has been detected in embryonic Müllerian ducts, human fallopian tubes, and ovarian carcinomas. However, little is known about its expression in other areas of the female genital tract. In this study, we used immunohistochemistry (IHC) to examine PAX8 expression in the normal uterine corpus and cervix, malignant tumors arising from these sites, and malignant effusions. We reported here that PAX8 was also detected in endometrial epithelial cells and endocervical glands, with a lower expression level in the latter, but not in the stromal cells of these areas. All endometrial carcinomas (N = 52) were positive for PAX8, whereas endocervical adenocarcinomas (N = 5) and uterine leiomyosarcomas (N = 3) were negative for PAX8. PAX8 was detected in 70% (22/31) and 68.8% (11/16) of metastatic carcinomas of the ovary and endometrium in serous effusions, respectively. No PAX8 was detected in carcinomas of nongynecologic origin or noncarcinomas (N = 71) in serous effusions except in one renal-cell carcinoma and one carcinoma of unknown primary in a woman. In addition, papillary serous carcinomas of the peritoneum (N = 10) were diffusely positive for PAX8, implying a Müllerian origin similar to malignant tumors in the female genital tract. Our findings suggest that PAX8 is an additional IHC marker for carcinomas of Müllerian origin hence we recommend including PAX8 for evaluation of malignant serous effusions in women, especially when tumors of Müllerian origin are in the differential diagnosis.

Value of PAX8, PAX2, claudin-4, and h-caldesmon immunostaining in distinguishing peritoneal epithelioid mesotheliomas from serous carcinomas

“…13,27 In a combined review of 713 primary and 118 metastatic ovarian serous carcinomas from 10 published studies, 650 (91%) and 107 (91%), respectively, were reported to be PAX8 positive. 13,[23][24][25][26][28][29][30][31][32] These results are comparable to those in the present investigation in which 14 (93%) of the 15 primary and 28 (93%) of the 30 metastatic ovarian serous carcinomas were found to express PAX8. To my knowledge, only one study on the expression of PAX8 in peritoneal epithelioid mesotheliomas has been published.…”

Assessment of the Utility of PAX8 Immunohistochemical Stain in Diagnosing Endocervical Glandular Lesions

“…Earlier studies showed that PAX8 positivity ranges from 97% to 100% in AIS and 0% to 87% in ECA. [1][2][3][4][5][6][7][8][9] The discrepancies among various studies may be attributable to several factors; the first is small sample size. Our study included 43 ECA (combined 2 cohorts) and 16 AIS, and is one of the largest studies.…”

“…PAX8 is usually expressed in Müllerian tumors and not expressed in many non-Müllerian tumors, including breast, colon, and gastroesophageal cancers. 1,3 Even though PAX8 can also be expressed in kidney, thyroid, and thymus neoplasms, usually these tumors can be differentiated from Müllerian tumors based on morphologic features. 1 During the formation of the reproductive system, paramesonephric ducts (also called Müllerian ducts) differentiate into the oviduct, uterus, cervix, and upper one-third of the vagina.…”

“…2 Furthermore, PAX8 was expressed in 97% to 100% of adenocarcinoma in situ (AIS) and in 0% to 87% of endocervical adenocarcinoma (ECA) specimens (summarized in Table 1). 1,[3][4][5][6][7][8][9] The goal of this study was to evaluate PAX8 expression by immunohistochemistry (IHC) in endocervix.…”

Tubal origin of ‘ovarian’ low-grade serous carcinoma

“…18 PAX8 expression is present in the secretory, but not ciliated epithelial cell population of the normal human fallopian tube, 19 and may play a role in differential diagnosis of ovarian epithelial cancers from histologic mimics. [19][20][21][22][23] Calretinin is a recognized mesothelial cell marker, which has been successfully applied to differentiate ovarian serous carcinomas from mesotheliomas, although a few ovarian high-grade serous carcinomas can have weak and focal positivity. [24][25][26] Tubulin identifies cellular surface cilia, and is therefore an appropriate marker to identify ciliated cells.…”