Ovarian Tumors Differ, Treatment Could Vary
Ovarian tumors classified as serous borderline or low malignant potential (LMP) are not early precursors in the development of aggressive ovarian cancer, but may instead be part of an entirely different class of tumors, according to a study reported in Cancer Research.
In addition, genes that were identified in this study as being expressed, or active, in these different classes of tumors could help identify targets for more specific diagnostics and therapies to treat this disease.
LMP is different than serous high-grade ovarian tumors (more aggressive tumors) yet shares remarkable similarities with serous low-grade ovarian tumors (less aggressive tumors), the researchers say.
Both serous high-grade and low-grade ovarian tumors are types of invasive ovarian cancer. Whether serous LMP tumors can give rise to invasive ovarian cancers has been controversial.
The most common type of ovarian cancer arises from the epithelial cells that line the surface of the ovary.
Epithelial ovarian tumors, approximately 50 percent of which are classified as serous (the cells have glandular features), constitute 80 percent of all ovarian tumors.
The classification of invasive serous ovarian tumors as either low-grade or high-grade is an indication of the clinical course of the disease, with high-grade tumors having the poorest prognosis.
Among gynecologic malignancies, ovarian cancer has the highest rate of mortality in women in the US with an estimated 22,220 new cases in 2005 and over 16,000 deaths.
The study was conducted by a research team that included scientists from the National Cancer Institute (NCI), the Dana-Farber Cancer Institute, and the M.D. Anderson Cancer Center.
Using a gene expression technique that reveals which genes are turned on or off in a cell, the researchers identified distinct differences between the gene expression profiles of LMP tumors and high-grade ovarian malignancies.
The gene expression results suggest that serous low-grade ovarian tumors are more similar to LMP tumors than to serous high-grade ovarian cancers and that different biochemical pathways may be involved in the development of LMP and low-grade tumors compared to high-grade tumors.
"Patients with serous low-grade or high-grade ovarian tumors currently receive the same treatment, which is surgery followed by chemotherapy," says Dr. Michael Birrer, study leader and head of the Molecular Mechanism Section at NCI.
"However, the finding that low-grade tumors are more similar to LMP tumors has significant therapeutic implications," says Dr. Birrer.
"Women with low-grade invasive tumors may benefit from therapies that are different from those given to patients with high-grade tumors," he remarks. "Furthermore, the biochemical pathways identified in this study may provide targets for more rational therapies for these different tumor types."
Dr. David M. Gershenson, a study co-author from M.D. Anderson Cancer Center, notes, "The classification of invasive serous ovarian tumors as either low-grade or high-grade is an indication of the clinical course of the disease with high-grade tumors having the poorer prognosis."
This study compared gene expression in ovarian tumors and normal epithelial cells. High-grade tumors over-expressed genes that control various cell functions related to the development of cancer.
These genes included those that control cell growth or cause DNA instability, as well as genes that can silence the expression of other genes, information that may provide important clues about why certain tumors are more aggressive than others.
In contrast, low-grade and LMP tumors did not overexpress these genes, and the gene expression profiles of LMP and low-grade tumors were similar. LMP tumors were characterized by the expression of growth control pathways, such as the p53 pathway in the cell.
These findings suggest that distinct biological mechanisms may be involved in the initiation of LMP and high-grade tumors and that some LMP tumors may give rise to invasive low-grade tumors.
"This study analyzed over 40,000 genes that were expressed in these different ovarian tumor types. Using the gene expression profiles we can determine the relationship between these tumors," says Dr. Birrer.
The tumors analyzed in this study included a total of 80 primary ovarian tumors. Of these, 20 were LMP tumors, all of which were classified as grade 0 and half of which 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.
A second study, reported in Archives of Internal Medicine, indicates that women who drink at least two cups of tea a day can reduce their risk of developing ovarian cancer by almost 50 percent.
There has been some experimental evidence that green and black tea might lower the risk of some cancers, but this is one of the few studies that has looked at the ability of tea to reduce the risk of ovarian cancer, the researchers note.
In their study, Susanna C. Larsson and Alicja Wolk, of the National Institute of Environmental Medicine at the Karolinska Institute in Stockholm, looked at 61,057 women who were 40 to 76 years old.
"We found a lower risk of ovarian cancer associated with greater tea consumption," says Larsson.
Larsson and Wolk found that women who drank at least two cups of tea a day reduced their risk of developing ovarian cancer by 46 percent.
"Each additional cup of tea per day was associated with an 18 percent lower risk of ovarian cancer," the authors report.
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