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Oviduct-specific glycoprotein is a molecular marker for invasion in endometrial tumorigenesis identified using a relevant mouse model.

TitleOviduct-specific glycoprotein is a molecular marker for invasion in endometrial tumorigenesis identified using a relevant mouse model.
Publication TypeJournal Article
Year of Publication2009
AuthorsWang H, Joshi A, Iaconis L, Solomon GJ, Xiang Z, Verhage HG, Douglas W, Ronnett BM, Ellenson LHedrick
JournalInt J Cancer
Volume124
Issue6
Pagination1349-57
Date Published2009 Mar 15
ISSN1097-0215
KeywordsAdaptor Proteins, Signal Transducing, Animals, Disease Models, Animal, DNA Mutational Analysis, DNA Primers, Endometrial Neoplasms, Exons, Fallopian Tubes, Female, Genotype, Loss of Heterozygosity, Mice, Mice, Knockout, Neoplasm Invasiveness, Neoplasm Metastasis, Nuclear Proteins, PTEN Phosphohydrolase, Tumor Markers, Biological
Abstract

The light microscopic distinction between complex atypical hyperplasia (CAH) and invasive endometrioid carcinoma (UEC) on endometrial sampling is problematic and often has significant clinical implications. Using mouse models of endometrial tumorigenesis based on two of the most common molecular alterations found in primary human UEC we sought to characterize the transition from CAH to carcinoma to identify clinically useful biomarkers. We used the previously described Pten(+/-); Mlh1(-/-) mouse model. DNA was isolated from microdissected lesions (CAH and carcinoma) and analyzed for LOH and mutations of Pten and additional candidate genes. To identify novel candidate genes associated with invasion, global gene expression profiles were compared from uteri with extensive CAH and carcinoma. The majority of CAHs and carcinomas, arising in this model showed biallelic inactivation of Pten mediated through LOH or intragenic mutation of the wild-type allele suggesting that complete loss of Pten is insufficient for the development of carcinoma. The global gene expression studies detected increased expression of oviduct-specific glycoprotein (OGP) in carcinoma as compared with CAHs. This finding was validated using immunohistochemical staining in a collection of primary human UECs and CAHs. Our studies identify a molecular marker for invasive endometrial cancer that may have clinical significance, and highlight the usefulness of this mouse model in not only understanding the genetic underpinnings of endometrial carcinoma, but as a tool to develop clinically relevant biomarkers.

DOI10.1002/ijc.24022
Alternate JournalInt. J. Cancer
PubMed ID19101990
PubMed Central IDPMC2680255
Grant ListR01 CA095427 / CA / NCI NIH HHS / United States
R01 CA095427-05 / CA / NCI NIH HHS / United States
R01 CA095427-09 / CA / NCI NIH HHS / United States
R01CA095427 / CA / NCI NIH HHS / United States

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