"As the aging population continues to grow, there is an urgent need to develop identification and treatment methods for intraepithelial neoplasia," said Scott Lippman, M.D., of the M.D. Anderson Cancer Center, Houston, Tex.
"We are hoping studies, like the data presented today, will continue to advance our knowledge and bring us closer to early screening methods for these deadly diseases," he added.
Correlation of Proliferation, Apoptosis and Nuclear and Glandular Features with Development of Prostatic Intraepithelial Neoplasia (PIN) and Prostate Cancer (Abstract 1255)
Researchers at the Roswell Park Cancer Institute, Buffalo, NY, and the University of Arizona Cancer Center in Tucson examined several factors that may be important in the development of prostate cancer, including nuclear and glandular features of prostate tissue, cell proliferation (reproduction) and cell apoptosis (cell death). Many studies have suggested that high-grade prostatic intraepithelial neoplasia (HGPIN, abnormal growth in the glands or ducts of the prostate) is a precursor to prostate cancer, and it has been recommended as a significant target for prostate cancer chemoprevention. As the most frequently diagnosed cancer in the United States and the second leading cause of cancer death for men, prostate cancer receives much attention, and prevention methods are in high demand.
Researchers distinguished abnormalities in cell changes in four different tissue diagnoses: normal cells, low grade PIN (LGPIN), HGPIN, and cancer. Using machine vision, researchers identified more than 100 nuclear and glandular features, including nuclear size, roundness, optical density, number of gaps and mean gap size. Machine vision is an image analysis system for use in determining differences in cancerous tissue on a glandular and nuclear level. Several nuclear features from machine vision showed a significant difference in HGPIN and cancer compared to normal, and nuclear roundness showed a significant difference in cancer compared to normal. As expected, there also was a difference in the cell reproduction rate between normal tissue and all other tissue diagnoses. Specifically, the rate increased from LGPIN to HGPIN to cancer, indicating that reproduction increases as tissue becomes more cancerous.
There was a significant increase from the apoptosis rate of normal tissue to that of cancer tissue, but apoptosis was very low in both LGPIN and HGPIN, and thus no conclusion could be drawn for the PIN cases. In addition, apoptosis rates did not distinguish tissue histology (structure) as clearly as reproduction. Observations of increases in both reproduction and apoptosis are consistent with animal studies.
"While apoptosis may not be a leading factor in prostate cancer development, machine vision is a good marker for discerning subtle nuclear changes that occur during disease development and progression," said Rochelle Ondracek, Ph.D., of the Roswell Park Cancer Institute, and lead author of the study.
"Based on the results of our study, in combination with other data, we believe that prostatic intraepithelial neoplasia may be a significant target for prostate cancer chemopreventive strategies, and that more research should be conducted to confirm this novel approach."
Exploratory Study of Ovarian Intraepithelial Neoplasia (Abstract 1563)
To better understand the role of ovarian intraepithelial neoplasia (OIN, abnormal growth in the glands or ducts of the ovary) in promoting the development of ovarian cancer, researchers from the Arizona Cancer Center in Tucson examined the disorder, testing three main hypotheses.
They first theorized that in normal-appearing ovarian surface epithelia, changes in the nuclear chromatin pattern indicate the presence of an ovarian abnormality. The second hypothesis suggested that such changes might already be present on the surface of ovaries that are free of lesions in women who are at increased risk for ovarian cancer. The last theory argued that some changes might occur in the underlying stroma (connective tissue).
"Ovarian cancer too often is a deadly disease for women since no reliable early detection methods exist," said Molly Brewer, D.V.M., M.D., M.S., of the Arizona Cancer Center, and lead author of the study.
"In our study, we observed changes on the ovarian surface and in the underlying tissues that we believe are sufficiently distinct to have potential as a diagnostic and prognostic marker for both early detection and prevention," she said.
Results from this study have shown that normal ovarian surfaces that are hiding a cancerous lesion can develop changes in the nuclear chromatin pattern consistent with a second phenotype (visible properties of an organism that are produced by the interaction of the genotype and the environment), something currently not accurately detected visually or histologically. The phenotype is also present in women at increased risk for ovarian cancer, suggesting it may represent a pre-malignant process. Secondarily, researchers found that in the stroma, a subpopulation of cells representing a second phenotype may also assist in identifying those at increased risk for ovarian cancer and those with ovarian cancer.
To investigate the hypotheses, researchers carefully collected ovaries from normal women, women at high risk of developing ovarian cancer, and ovaries with areas of histologically normal tissue adjacent to ovarian cancer. A total of 3,290 epithelial nuclei and 3,510 stromal nuclei were segmented and evaluated.
In 2003, an estimated 25,400 new cases of ovarian cancer will be diagnosed in the United States, accounting for nearly four percent of all cancers among women. Ovarian cancer ranks second among gynecologic cancers and causes more deaths than any other cancer of the female reproductive system. More than 14,000 women will die from ovarian cancer this year.
Founded in 1907, the American Association for Cancer Research is a professional society of more than 21,000 laboratory, translational, and clinical scientists engaged in cancer research in the United States and in more than 60 other countries. AACR's mission is to accelerate the prevention and cure of cancer through research, education, communication, and advocacy. Its principal activities include the publication of five major peer-reviewed scientific journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. AACR's annual meetings - next year in Orlando, Fla., March 27-31 - attract more than 15,000 participants who share new and significant discoveries in the cancer field. Specialty meetings like this one, held throughout the year, focus on the latest developments in all areas of cancer research.