Expression of PAX2 in papillary serous carcinoma of the ovary: immunohistochemical evidence of fallopian tube or secondary Müllerian system origin?

Abstract

PAX2 is a urogenital developmental transcription factor expressed in the Wolffian ducts, developing kidneys, and Mü llerian ducts during embryonic stage. Its function in renal development is well documented and its clinical application in the diagnosis of lesions of renal origin has been reported recently. However, information on its role in the Mü llerian-derived genital tract is sparse. In this study, we investigated the expression of PAX2 in human female genital tract using immunohistochemistry. We demonstrated that PAX2 was expressed specifically in the epithelial cells of fallopian tube, endometrial and endocervical glands, but not in the stromal tissues in these areas. PAX2 was detected in secondary Mü llerian structures in the ovary, such as endometriotic and endosalpingiotic glands and rete ovarii, but not in ovarian surface epithelium, surface epithelium-derived inclusion cysts, stroma, or sex-cord-derived structures such as follicles, oocytes, and corpus luteum. In addition, PAX2 was detected in 67% of ovarian papillary serous carcinomas (N ¼ 36) but rarely in peritoneal malignant mesotheliomas, with two exceptions (N ¼ 54). Interestingly, the two PAX2-positive 'peritoneal malignant mesotheliomas' were from female patients and were positive for estrogen receptor. The significance of expression of PAX2 and estrogen receptor in these cases is under investigation. Taken together, we suggest that PAX2 is a novel Mü llerian-specific epithelial marker when used in proper clinical settings. Identification of PAX2 in the majority of papillary serous carcinomas of the ovary but not in the ovarian surface epithelium or epithelium-derived inclusion cysts suggests that this malignant epithelial tumor may be directly derived from the primary or secondary Mü llerian epithelium in or surrounding the ovary, rather than from the surface epithelium or its derivatives.

Nephrogenic adenoma identified on urine cytology using PAX‐2 immunostaining

“…Renal cell carcinoma 12,13 and NA 1,9 are positive for PAX2, whereas prostate adenocarcinoma and urothelial carcinoma are negative. 9 The epithelial cells of the fallopian tube, uterus, cervix, and papillary serous carcinoma of the ovary are positive for PAX2, 14 but these cells rarely appear in urine. Therefore, it is conceivable that PAX2 positive cells in urine may include normal renal tubular cells, NA cells, and cells from renal cell carcinoma.…”

Divergent Roles of PAX2 in the Etiology and Progression of Ovarian Cancer

“…Although PAX2 expression in ovarian cancers has been extensively reported (4,7,9,15), its role in ovarian tumorigenicity is uncertain, due to a limited number of experimental reports and their conflicting outcomes. Notably, PAX2 knockdown in some ovarian cancer cell lines increased apoptosis and reduced cellular proliferation and/or migration (9,15).…”

“…PAX2 is a member of the paired-box binding protein family (PAX) of transcription factors and is expressed in the developing urogenital tract, inner ear, and brain (5). After development, Pax2 expression is usually attenuated (5,6), except in putative stem cells in breast, kidney, and female reproductive tract (4,6,7), where it promotes cell survival and tissue regeneration (8).…”

Genetic association between PAX2 and mullerian duct anomalies in Han Chinese females

“…Pax2 was first detected in the intermediate mesoderm, which would evolve into the mullerian duct, Wolffian duct, kidney, and other derivatives of the urogenital system afterwards. Subsequently, Pax2 was found in both ductal and mesenchymal components and played a vital role in mesenchyme-to-epithelium transition during genital tract and kidney development [16,17,26]. As we mentioned before, the function of PAX2 in the urogenital system was also further investigated in mice models.…”

“…As a crucial factor, PAX2 is widely expressed in the epithelial cells of the mullerian-derived reproductive tract and the condensing mesenchyme of the kidney, which participates in the development and differentiation of the vertebrate urogenital system [15,16]. The important function of PAX2 in the urogenital system has been further demonstrated through animal models.…”