Gain of OGP, an Estrogen-Regulated Oviduct-Specific Glycoprotein, Is Associated with the Development of Endometrial Hyperplasia and Endometrial Cancer

Abstract

Purpose: Lesions in the endometrium are difficult to differentially diagnose. The present study examined whether oviduct-specific glycoprotein is differentially expressed in normal, hyperplastic, and malignant endometrium.Experimental Design: The expression of oviduct-specific glycoprotein was characterized by immunohistochemical methods with whole sections of endometrium from 90 women. An endometrial cancer tissue microarray with 200 cases of endometrial cancer was also assessed for oviductspecific glycoprotein, estrogen receptor, and PTEN expression.Results: In normal endometrium, there was focal oviduct-specific glycoprotein expression in the basalis layer, where the stem cells reside, in 10 of 15 cases. On average, atypical hyperplastic endometria stained more intensely than hyperplastic endometria (P ‫؍‬ 0.017), whereas the percentage of positively stained cells was not significantly different. The mean staining indices (intensity ؋ percentage of positive cells score) for hyperplasia and atypical hyperplastic were 4.7 and 5.5 and were significantly higher than staining indices seen in normal cycling endometria or welldifferentiated endometrioid endometrial carcinomas (P < 0.0001 and P < 0.001, respectively). The endometrial cancer tissue microarray showed that of 139 endometrioid endometrial carcinomas, 11 cases were strongly oviduct-specific glycoprotein positive, whereas the other 128 cases were negative or weakly positive. Analysis of Kaplan-Meier curves with log-rank statistics showed a trend toward significance, with strong oviduct-specific glycoprotein staining serving as a predictor of good prognosis (P ‫؍‬ 0.1). There was a significant positive correlation between oviduct-specific glycoprotein staining and loss of PTEN in the cases of endometrial cancer (P ‫؍‬ 0.004).Conclusions: Oviduct-specific glycoprotein may be a useful diagnostic adjunct to more accurately classify premalignant and early malignant change in the endometrium, improving on the current irreproducible histologic classification system.

Oviductal Glycoprotein (OVGP1, MUC9)

“…22 We reported previously that in tumor tissue microarrays, rare endometrial carcinomas were positive for OVGP1. 19,20 These observations agree with the results of the present study. Interestingly, in an analysis of gene expression in early-stage ovarian cancer, mucinous and clear cells histotypes could be distinguished from the others regardless of tumor grade.…”

“…As detection antibody, we used a highly specific polyclonal rabbit antiYhuman OVGP1 antibody. 13,19,20 Construction of Double-Determinant (Sandwich) Enzyme-Linked Immunosorbent Assay…”

“…19 In an immunohistochemical study of endometrial carcinomas, OVGP1 was present in 35% of atypical endometrial hyperplasias but in less than 10% of endometrioid cancers and none of the nonendometrioid carcinomas. 20 In the present study, we investigated the possibility that OVGP1 could be detected in the serum of women with ovarian cancer, and serve as a diagnostic marker. At the onset of this study, no monoclonal antibodies and no assay system for human OVGP1 were available.…”

NAC1, a potential stem cell pluripotency factor expression in normal endometrium, endometrial hyperplasia and endometrial carcinoma

“…NAC1 may play an important role in estrogen-induced cell growth in normal cyclic endometrium. It may be less important in endometrial cancers that have lost estrogen signaling and are stimulated by other oncogenic pathways (28,32,33). While many endometrial cancers lose NAC1 expression, some high grade tumors continue to produce it.…”

Identification of cellular isoform of oviduct-specific glycoprotein: role in oviduct tissue remodeling?

“…Interestingly, like tubulin up-regulation at ciliogenesis (Shea and Walsh 1987), OGP is coordinately regulated by genes involved in differentiation and/or proliferation suppression (Bauersachs et al 2004). Further, it is expressed ex situ in the endometrium (Punyadeera et al 2005;Talbi et al 2006), wherein the loss is correlated with neoplastic progression involving de-differentiation and proliferation (Woo et al 2004). Additionally, in vitro studies have revealed a close link between OGP mRNA levels and the maintenance of polarity and differentiation (Reischl et al 1999).…”