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A PROTEIN ANTIGEN HOLDS PROMISE FOR BETTER CERVICAL CANCER DETECTION, UC IRVINE RESEARCHER REPORTS
Substance Helps Identify Early Cervical Abnormalities
Irvine, Calif., March 23, 1998 ó An easily detectable protein may hold the key to more reliably warning women about early cell abnormalities in the cervix before they get life-threatening cancer, a UC Irvine researcher reported today.
Testing Pap smears of cervical cells for an antigen called MN/CA9 can tip scientists off to precancerous cervical lesions and malignant growths that may go undiscovered with current diagnostic techniques, said Eric J. Stanbridge, a UCI College of Medicine cancer researcher. Stanbridge spoke of his findings at the American Cancer SocietyÃs annual meeting for science writers in Newport Beach, Calif.
Stanbridge and his colleague, Dr. Shu-Yuan Liao, will begin clinical trials for a new MN/CA9 test in the coming months, pending final approval by the National Cancer Institute. Liao is an associate clinical professor in the UCI College of Medicine and a pathologist at St. Joseph Hospital in Orange, Calif.
Worldwide, cervical cancer is one of the most common malignancies in women, and is second only to breast cancer in its incidence and mortality. In developed countries, including the United States, the introduction of the Papanicolaou (Pap) smear test has greatly reduced the incidence of cervical cancer. Despite this success, false negative results can still occur due to human errors in the lab or cell sampling errors.
"The reported incidence of false negatives varies considerably, but any incident is potentially serious for the patient involved," Stanbridge said.
An additional test to detect the MN/CA9 antigen, used in conjunction with a standard Pap smear, holds the potential to help physicians diagnose cell abnormalities more accurately.
The MN/CA9 antigen was first identified in 1992 by Czech and Slovak scientists, who found it in a cervical cancer cell line known as HeLa. They contacted Stanbridge because he was one of the pioneers of an experimental system to suppress tumor cells using somatic cell hybridization: the fusion of malignant human cells with normal human cells, resulting in transformed cells in which malignancy is suppressed. One of the cell lines Stanbridge used for such research was HeLa. The MN/CA9 antigen, a protein produced by HeLa cells, also is present in virtually all cervical cancer growths, though its function is unknown.
In a standard Pap smear test, experienced cytologistsóscientists with expertise in the structure and function of cellsólook very closely at cells taken with a swab or cytobrush from a womanÃs cervix, smeared onto a slide and stained with the Papanicolaou stain. They judge whether the cells are outside normal limits of shape and other characteristics, indicating a woman could have anything from a precancerous lesion to a malignant tumor. When using the new test method, scientists can take those same cells and apply an antibody stain to them that results in a brown stain when MN/CA9 is present.
Stanbridge and Liao found in a recent study that MN/CA9 showed up in some cells identified in Pap tests as within normal limits. When they looked at the actual cervical tissue the cell samples came from, they found several dysplasiasóirregular cells prone to turning cancerousóand adenocarcinomas, or glandular-related cancers. In some cases, women whose cell samples looked completely normal but were positive for MN/CA9 were found to have precancerous or cancerous cervical lesions. When Stanbridge and Liao found no MN/CA9 in the Pap smears, they found no evidence of lesions in the originating tissue.
One of the challenges of using Pap tests, Stanbridge said, is that cytologists sometimes find that cells donÃt look normal, but they donÃt look malignant or dysplastic, either. One group of such cells is termed "atypical glandular cells of undetermined significance" (AGUS). Gynecologic oncologists face a dilemma when they see AGUS results, because screening surveys show about 40 percent of patients with AGUS results have a significant lesion that is dysplastic or cancerous, and 60 percent do not. About 250,000 U.S. women a year have Pap tests with results showing AGUS (about .5 percent of all Pap smears), but doctors canÃt determine if patients have significant lesions without costly, invasive procedures.
Suspecting MN/CA9 could shed light on vague AGUS test results, Stanbridge and Liao conducted a study to look for the antigen in AGUS Pap smear samples. Their findings were clear-cut: Smears from patients who had been found to have significant cervical lesions all showed MN/CA9 staining, and all smears that showed no specific MN/CA9 staining corresponded to tissue that showed no signs of dysplasia or carcinoma.
Stanbridge and Liao have not yet conducted a study to correlate MN/CA9 and a second form of unusual cells, "atypical squamous cells of undetermined significance" (ASCUS), but Stanbridge said the MN/CA9 technique appears promising for those cells as well.
Stanbridge has taught and conducted research at UC Irvine since 1975. His work focuses on tumor suppressor genes and genes that contribute to the onset and continued growth of cancer.
More information about Eric StanbridgeÃs research is available on his faculty home page.
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