Genetic findings affect diagnosis, treatment of ovarian cancer

A new study from the National Cancer Institute suggests that ovarian tumors classified as serous borderline or serous low malignant potential are not early precursors in the development of aggressive ovarian cancer. They may instead belong to an entirely different class of tumors.

Genes that were identified in this study as being expressed in these different classes of tumors could help identify targets for more specific diagnostic methods and therapies to treat this disease, according to an NCI press release.

Low malignant potential tumors are characterized by malignant features and metastatic potential yet display a benign clinical course. Such tumors are more aggressive than serous high-grade ovarian tumors but were found to share genetic similarities with the less aggressive serous low-grade ovarian tumors.

Both serous high-grade and low-grade ovarian tumors are types of invasive ovarian cancer. Whether low malignant potential tumors can give rise to invasive ovarian cancers has been a controversial issue.

Dr. Tomas Bonome and colleagues from the NCI, the Dana-Farber Cancer Institute in Boston, and the M.D. Anderson Cancer Center in Houston compared gene expression in ovarian tumors and normal epithelial cells. They found that high-grade tumors overexpressed genes that control various cell functions related to the development of cancer (Cancer Research 2005;65[22]:10602-10612).

In contrast, low-grade and low malignant potential tumors did not overexpress these genes, and the gene expression profiles of low malignant potential and low-grade tumors were similar.

These findings suggest that distinct biological mechanisms may be involved in the initiation of low malignant potential and high-grade tumors and that some low malignant potential tumors may give rise to invasive low-grade tumors.

"Patients with serous low-grade or high-grade ovarian tumors currently receive the same treatment, which is surgery followed by chemotherapy. However, the finding that low-grade tumors are more similar to low malignant potential tumors has significant therapeutic implications," said senior author Dr. Michael Birrer, head of the molecular mechanism section at the NCI, in the press release.

Women with low-grade invasive tumors may benefit from therapies that are different from those given to patients with high-grade tumors. The biochemical pathways identified in this study may provide targets for more rational therapies for these different tumor types, Birrer said.

The most common type of ovarian cancer arises from the epithelial cells that line the surface of the ovary. Epithelial ovarian tumors constitute 80% of all ovarian tumors. Approximately 50% of them are classified as serous.

The classification of invasive serous ovarian tumors as either low grade or high grade is an indication of the clinical course of the disease. High-grade tumors have the poorest prognosis, according to coauthor Dr. David M. Gershenson, a gynecologic oncologist at M.D. Anderson.

The tumors analyzed in this study included 80 primary ovarian tumors. Of the 20 that were low malignant potential tumors, all were classified as grade 0 and half were classified as stage I. The remaining 60 tumors were invasive cancers. The majority of these were grade 3, stage III. Gene expression was also assessed in 10 samples of normal ovarian epithelial tissue.

The researchers obtained cancer cells by microdissecting the tumor. Therefore, the genes identified were expressed specifically in the ovarian cancer cell and may provide insights into how genes within cancer cells modulate normal cells to support malignant tumor growth, according to the study.

For more information from the Diagnostic Imaging archives:

Task force says no to routine genetic testing

Enhanced ultrasound reveals gynecological disorders

FDG-PET predicts ovarian cancer response to chemotherapy

Reporter gene imaging illustrates molecular events