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

Department of Pathology, Columbia University Medical Center, New York, NY 10032, USA.
Modern Pathology (Impact Factor: 6.19). 09/2007; 20(8):856-63. DOI: 10.1038/modpathol.3800827
Source: PubMed


PAX2 is a urogenital developmental transcription factor expressed in the Wolffian ducts, developing kidneys, and Müllerian 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 Müllerian-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 Müllerian 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=36) but rarely in peritoneal malignant mesotheliomas, with two exceptions (N=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 Müllerian-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 Müllerian epithelium in or surrounding the ovary, rather than from the surface epithelium or its derivatives.

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Available from: Alain charles Borczuk, Aug 04, 2014
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    • "(ii) The three most prevalent ovarian cancer subtypes are morphologically reminiscent of different Müllerian duct-derived structures [36]). (iii) Well-established ovarian cancer biomarkers such as CA125 [37], HE4 [38] and PAX2 [39], are proteins expressed by endometrial and tubal epithelial cells though not in ovarian surface epithelium [37], [38], [39]. In view of our findings, an admittedly speculative though stimulating hypothesis can be formulated. "
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    ABSTRACT: In fertile women, the endometrium undergoes regular cycles of tissue build-up and regression. It is likely that uterine stem cells are involved in this remarkable turn over. The main goal of our current investigations was to identify slow-cycling (quiescent) endometrial stem cells by means of a pulse-chase approach to selectively earmark, prospectively isolate, and characterize label-retaining cells (LRCs). To this aim, transgenic mice expressing histone2B-GFP (H2B-GFP) in a Tet-inducible fashion were administered doxycycline (pulse) which was thereafter withdrawn from the drinking water (chase). Over time, dividing cells progressively loose GFP signal whereas infrequently dividing cells retain H2B-GFP expression. We evaluated H2B-GFP retaining cells at different chase time points and identified long-term (LT; >12 weeks) LRCs. The LT-LRCs are negative for estrogen receptor-α and express low levels of progesterone receptors. LRCs sorted by FACS are able to form spheroids capable of self-renewal and differentiation. Upon serum stimulation spheroid cells are induced to differentiate and form glandular structures which express markers of mature műllerian epithelial cells. Overall, the results indicate that quiescent cells located in the distal oviduct have stem-like properties and can differentiate into distinct cell lineages specific of endometrium, proximal and distal oviduct. Future lineage-tracing studies will elucidate the role played by these cells in homeostasis, tissue injury and cancer of the female reproductive tract in the mouse and eventually in man.
    PLoS ONE 07/2012; 7(7):e40691. DOI:10.1371/journal.pone.0040691 · 3.23 Impact Factor
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    • "PAX2 and PAX8 have been detected in 64 to 100% of nonmucinous ovarian cancers, and in 74 to 90% of primary and metastatic renal cell carcinomas (Bowen et al., 2007; Tong et al., 2007; Nonaka et al., 2008; Chivukula et al., 2009; Zhai et al., 2010; Laury et al., 2011; Tacha et al., 2011). The absence or rareness of PAX2 and PAX8 in many other types of cancers such as colorectal carcinomas and mesotheliomas has raised the possibility that these proteins could be useful markers for differential diagnosis (Tong et al., 2007; Zhai et al., 2010; Laury et al., 2011; Tacha et al., 2011), but this depends on the appropriate setting. Ovarian metastasis from renal cell carcinoma and renal metastasis from ovarian carcinoma are rare. "

    Ovarian Cancer - Basic Science Perspective, 02/2012; , ISBN: 978-953-307-812-0
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    • "Chen et al. (2010) have also shown that androgen-dependent re-expression of Pax2 occurs after castration in male mice. PAX2 is expressed in ovarian cancers, in renal cell carcinomas (RCC), and in some bladder carcinomas (Muratovska et al., 2003; Tong et al., 2007; Herlitz et al., 2008). In these cell types it appears to be important for tumor cell survival (Muratovska et al., 2003; Hueber et al., 2006), which has recently been shown to be because PAX2 regulates ADAM10 (Doberstein et al., 2011), and in RCC PAX2 expression is promoted by the loss of VHL and hypoxia (Luu et al., 2009). "
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    ABSTRACT: PAX genes have been shown to be critically required for the development of specific tissues and organs during embryogenesis. In addition, PAX genes are expressed in a handful of adult tissues where they are thought to play important roles, usually different from those in embryogenesis. A common theme in adult tissues is a requirement for PAX gene expression in adult stem cell maintenance or tissue regeneration. The connections between adult stem cell PAX gene expression and cancer are intriguing, and the literature is replete with examples of PAX gene expression in either situation. Here we systematically review the literature and present an overview of postnatal PAX gene expression in normal and cancerous tissue. We discuss the potential link between PAX gene expression in adult tissue and cancer. In addition, we discuss whether persistent PAX gene expression in cancer is favorable or unfavorable.
    Frontiers in Genetics 01/2012; 3:6. DOI:10.3389/fgene.2012.00006
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