PAX2 expression in low malignant potential ovarian tumors and low-grade ovarian serous carcinomas

Tung, Celestine S.; Mok, Samuel C.; Tsang, Yvonne T.M.; Zu, Zhifei; Song, Huijuan; Liu, Jinsong; Deavers, Michael T.; Malpica, Anaís; Wolf, Judith K.; Lu, Karen H.; Gershenson, David M.; Wong, Kwong-Kwok

doi:10.1038/modpathol.2009.92

Cited by 79 publications

(64 citation statements)

References 34 publications

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“…OSE cells retain the potential to differentiate into epithelia resembling that of the Mullerian system (28,29) by, for example, induction of HOX gene expression (30). HOX and PAX genes are required for Mullerian development and are expressed in a subset of EOC but not in normal OSE cells (4,31). PAX2 is expressed in ciliated inclusion cysts, low-malignant potential, and LGSC (4), suggesting that gain of PAX2 expression promotes transformation (as shown in rat fibroblasts; ref.…”

Section: Discussionmentioning

confidence: 99%

“…PAX2 is not expressed in normal ovaries (4), suggesting that induction of its expression might be an early step in ovarian tumorigenesis. 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).…”

Section: Introductionmentioning

confidence: 99%

“…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).…”

Section: Introductionmentioning

confidence: 99%

“…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).…”

Section: Introductionmentioning

confidence: 99%

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

Al-Hujaily

Tang

Yao

et al. 2015

Cancer Prevention Research

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PAX2 is an essential transcription factor for development. Aberrant PAX2 expression in adult tissues is associated with carcinogenesis and experimental evidence shows that PAX2 generally exhibits oncogenic properties. Although PAX2 is not expressed in normal ovaries, it is highly expressed in low malignant potential and low-grade epithelial ovarian tumors, suggesting that PAX2 induction in ovarian surface epithelium (OSE) may contribute to transformation. Herein, we provide evidence that expression of PAX2 in normal murine OSE cells (mOSE) enhances their proliferation and survival and, with loss of p53, induces tumorigenicity. PAX2 expression in murine ovarian cancer cells enhanced or inhibited tumorigenicity, depending on the model system. In RM cells (mOSE transformed by K-RAS and c-MYC), PAX2 expression inhibited p53 and induced pERK1/2 and COX2, resulting in enhanced angiogenesis and decreased apoptosis of tumors arising from these cells. However, in a murine model of high-grade serous ovarian cancer (STOSE), PAX2 expression improved animal survival by reducing proliferation and metastasis, which correlated with increased Htra1 and decreased COX2. Thus, PAX2 may not be a classical oncogene or tumor suppressor but instead can act in either role by differential regulation of COX2 and/or HTRA1.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Al-Hujaily

Tang

Yao

et al. 2015

Cancer Prevention Research

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“…17,18 One of these genes, PAX2, has been shown to be down-regulated in both high-grade mü llerian (endometrioid or serous) pelvic carcinomas and in benign and neoplastic endometrium. 16,[19][20][21] Recently, we identified a second form of SCOUT in the oviduct that exhibited normal TP53 genotype but on further analysis, frequently showed a loss or reduction of PAX2 immunostaining. 14 In a comparison of serous cancers, benign controls, and benign tubes from women with germ-line BRCA1 or BRCA2 mutations, a higher frequency of these foci appeared strongly associated with malignancy.…”

Section: Discussionmentioning

confidence: 99%

PAX2-null secretory cell outgrowths in the oviduct and their relationship to pelvic serous cancer

et al. 2012

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With the exception of germ-line mutations in ovarian cancer susceptibility genes, genetic predictors for women destined for ovarian serous cancer cannot be identified in advance of malignancy. We recently showed that benign secretory cell outgrowths (SCOUTs) in the oviduct are increased in frequency with concurrent serous cancer and typically lack PAX2 expression (PAX2-null). The present study examined the relationship of PAX2-null SCOUTs to high-grade serous cancers by comparing oviducts from women with benign gynecologic conditions and high-grade serous cancers. PAX2-null SCOUTs were identified by immunostaining and computed as a function of location, frequency (F) per number of cross-sections examined, and age. Six hundred thirty-nine cross-sections from 35 serous cancers (364) and 35 controls (275) were examined. PAX2-null SCOUTs consisted of discrete linear stretches of altered epithelium ranging from cuboidal/columnar, to pseudostratified, the latter including ciliated differentiation. They were evenly distributed among proximal and fimbrial tubal sections. One hundred fourteen (F ¼ 0.31) and 45 (F ¼ 0.16) PAX2-null SCOUTs were identified in cases and controls, respectively. Mean individual case-specific frequencies for cases and controls were 0.39 and 0.14, respectively. SCOUT frequency increased significantly with age in both groups (P ¼ 0.01). However, when adjusted for age and the number of sections examined, the differences in frequency between cases and controls remained significant at P ¼ 0.006. This study supports a relationship between discrete PAX2 gene dysregulation in the oviduct and both increasing age and, more significantly, the presence of co-existing serous cancer. We propose a unique co-variable in benign oviductal epithelium-the PAX2-null SCOUT-that reflects underlying dysregulation in genes linked to serous neoplasia.

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Diagnostic utility of PAX8 and PAX2 immunohistochemistry in the identification of metastatic Müllerian carcinoma in effusions

Wiseman

Michael

Roh

2010

Diagnostic Cytopathology

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Morphologic distinction of Müllerian carcinomas from non-Müllerian carcinomas in effusion specimens by cytomorphology alone can be diagnostically challenging. Therefore, immunohistochemical adjuncts can be useful in differentiating Müllerian from non-Müllerian metastases. In this study, we evaluated the expression of PAX8 and PAX2 in malignant effusions collected from patients with known Müllerian and non-Müllerian carcinomas. Sections from cell blocks prepared from 152 effusion specimens (54 and 98 cases representing metastases from Müllerian and non-Müllerian primaries, respectively) were immunostained with rabbit polyclonal antibodies against PAX8 and PAX2. Immunopositivity was defined as the presence of strong nuclear staining in at least 25% of the tumor cells. Fifty-two (96%) and 13 (24%) of the 54 Müllerian carcinomas were positive for PAX8 and PAX2, respectively. PAX8 positivity was seen in only four (4%) of 98 non-Müllerian carcinomas; these represented metastasis from a large cell neuroendocrine lung carcinoma, papillary thyroid carcinoma, renal cell carcinoma, and acinic cell carcinoma of the parotid gland. PAX2 positivity was not seen in any of the non-Müllerian carcinomas. The results demonstrate that both PAX8 and PAX2 are highly specific markers for metastatic Müllerian carcinomas in cell block preparations from effusion specimens (96% and 100%, respectively). PAX8, however, is more sensitive than PAX2 in identifying Müllerian carcinomas in fluids (96% versus 24%). Overall, immunohistochemistry for PAX8 and PAX2 represent diagnostically useful adjuncts in identifying a Müllerian carcinoma as a source of a malignant effusion.

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PAX2 expression in low malignant potential ovarian tumors and low-grade ovarian serous carcinomas

Cited by 79 publications

References 34 publications

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

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

PAX2-null secretory cell outgrowths in the oviduct and their relationship to pelvic serous cancer

Diagnostic utility of PAX8 and PAX2 immunohistochemistry in the identification of metastatic Müllerian carcinoma in effusions

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