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U-M pathologist receives Department of Defense New Investigator Award

added 6/29/04

Ann Arbor - The majority of ovarian cancers are thought to arise from the single layer of cells on the surface or epithelium of the ovary. Although ovarian epithelial cancers or ovarian adenocarcinomas (OAs) may share a common origin, they look very different when examined under a microscope. Pathologists can recognize four major types of OAs – serous, mucinous, clear cell, and endometrioid – based on specific features on the tumor cells. However, these differences in histology do not correspond to different treatments for the disease. Rong Wu, M.D., a pathologist at the University of Michigan Comprehensive Cancer Center, wonders if perhaps they should.

Wu is about to undertake early studies to better understand how one of these four types of ovarian cancer, ovarian endometrioid adenocarcinoma (OEA), might develop and progress. Wu’s research concept has been recognized by the United States Department of Defense Ovarian Cancer Research Program with a New Investigator Award of $433,000 to develop a murine, or laboratory mouse, model to study OEAs.

Cancer evolves through a process that promotes the growth of cells with gene mutations that allow cancerous cells to survive and multiply. While these mutations are critical in virtually all cancer types, the specific genetic defects vary from one cancer type to another. In the case of ovarian cancer, some differences in gene mutations have been observed in each of the four histological types identified. Mutations of a specific gene encoding a protein called ß-catenin have been shown by Wu and others to occur frequently in OEA, but not in the other three histological types of ovarian cancer. Furthermore, ß-catenin mutation appears to play a critical role in transforming normal cells into cancerous ones, making this a target worthy of further study.

Many cancer types, including colon, lung, brain, breast and prostate have been successfully modeled using mice bred specifically for laboratory study. But most efforts to generate mouse models to study ovarian cancer have failed. Although recent attempts to generate transgenic mice that selectively express cancer-associated genes on the ovarian surface epithelium have met with some success, all thus far seem to result in ovarian cancers resembling the serous type. Wu will attempt to develop a new mouse model of the OEA type with features similar to the human form of the disease by expressing a mutant form of ß-catenin in the mouse ovarian surface epithelium.

In its most basic application, Wu hopes the study will help ovarian cancer research catch up with other areas of cancer research, where murine models are proving so helpful. “Mouse models of many cancer types have provided important insights into how tumors develop, progress and respond to treatment. Although our research is too basic for immediate clinical applicability, even this first step will be significant in advancing ovarian cancer research,” she says.

What does Wu see as the ultimate goal of the research? “Our study has the potential to help all ovarian cancer patients by increasing our understanding of the different types of ovarian cancer. It may eventually lead to type-specific preventive, diagnostic and treatment strategies for patients, although this outcome will likely take several years to achieve.”

To learn more about ovarian cancer and its treatment at the University of Michigan Comprehensive Cancer Center, call the Cancer AnswerLine™ at 800-865-1125.

For further information, contact Shelley Zalewski at (734) 936-9584 or szalewsk@umich.edu.

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