CCR Grand Rounds November 22: Dr. Paul Meltzer, Senior Investigator, Cancer Genetics Branch, National Human Genome Research Institute; "Using Genome Technologies to Find Biological Mechanisms in Cancer: Beyond Expression Profiling" November 29: Dr. Richard M. Caprioli, Stanley Cohen Professor of Biochemistry, Professor of Chemistry and Pharmacology, Director, Mass Spectrometry Research Center, Vanderbilt University; "The Role of Proteomics in Clinical and Biological Research: Direct Tissue Analysis by Mass Spectrometry" CCR Grand Rounds are held 8:30 to 9:30 a.m. at the NIH campus in Bethesda, Md., in the Clinical Center's Lipsett Amphitheater.

Ovarian Cancer Screening With Ultrasound and CA-125 Finds Cancer, But Also Many False-Positives

A new NCI study shows that screening methods such as transvaginal ultrasound (TVU) and testing for the protein biomarker CA-125 can detect ovarian cancer, but can also produce many false-positive test results. The report on preliminary results from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial appears in the November 15 American Journal of Obstetrics and Gynecology.

These results, the first on ovarian cancer screening from the ongoing multicenter PLCO Trial, are based on analysis of the participants' initial screening tests. CA-125 and TVU have been considered potential screening techniques, but studies to date have not shown that they can be effective and thus they are not currently recommended. The long-term goal of the PLCO Trial is to determine whether screening with TVU and/or CA-125 decreases ovarian cancer mortality in women ages 55 to 74.

Of the 28,816 women who underwent baseline screening, 1,338 (4.7 percent) had an abnormal TVU and 402 (1.4 percent) had an abnormal CA-125 blood test. Thirty-four women (0.1 percent) had abnormal results in both screening tests. Among the women with abnormal test results, 29 tumors were detected, 20 of which were invasive cancers.

"Ovarian cancer is a disease that is often fatal, and both patients and physicians are anxious to find ways to detect it at an earlier, more curable stage," said lead author Dr. Saundra Buys of the University of Utah. "However, the results from the initial year of screening show that TVU and CA-125 cannot currently be recommended for widespread use in the general population."

Gene Profiling Suggests New Classification for Ovarian Tumors

Researchers using DNA microarrays to analyze gene activity in several types of ovarian tumors have determined that a type called papillary serous low malignant potential (LMP) is distinctly different from high-grade ovarian tumors. Further, the results indicate that low-grade invasive ovarian tumors are more similar to LMP tumors than to high-grade ovarian tumors.

The team used a technique called laser capture microdissection to isolate tumor cells from about 80 ovarian tumor samples. Using the microarrays, the researchers identified genes involved in regulating cell growth and other critical activities that were overactive in high-grade tumors but not in the other types. The low-grade and LMP tumors had similar overall patterns of gene activity that were distinct from those of the high-grade tumors.

The findings, taken together, suggest that LMP and low-grade tumors may represent "a distinct classification of tumors rather than as precursors in the development of advanced high-grade malignancy," the researchers report in the November 15 Cancer Research.

The results could have implications for treatment. Currently, patients with low-grade tumors receive the same therapy as patients with high-grade tumors: surgery followed by chemotherapy. "It is not clear that women with low-grade ovarian tumors benefit from being treated with high-grade regimens," notes Dr. Michael Birrer, who heads NCI's Molecular Mechanism Section and led the study.

Being able to distinguish among different types of ovarian tumors might eventually allow women with low-grade serous tumors to have therapy specific to their cancer and be spared the side effects of combination chemotherapy used for high-grade tumors.

Most Men Can Father Children After Testicular Cancer

A majority of men treated for testicular cancer can naturally father children, concludes a study from Norway published in the November 2 Journal of the National Cancer Institute. The success rate varied from 81 percent for men followed with surveillance to 38 percent for men who were treated with high-dose chemotherapy. The overall success rate was 65 percent with a median follow-up of 11 years.

"[T]he ability to conceive and the time to conception reflected the intensity of treatment," write the researchers from five Norwegian cancer centers.

The team assessed 1,433 men treated for testicular cancer between 1980 and 1994. The participants were split into five treatment groups: the first received only orchiectomy (surveillance) while the others were treated with orchiectomy plus retroperitoneal lymph node dissection, radiotherapy, or low- or high-dose chemotherapy.

In an accompanying editorial, Dr. Scott Saxman, of NCI's Cancer Therapy Evaluation Program, writes that conventional retroperitoneal lymph node dissection, which frequently results in dry ejaculation, and high-dose chemotherapy (defined in the study as greater than 850 milligrams of cisplatin) are no longer standard treatments. They have been replaced by nerve-sparing surgery and lower overall doses of chemotherapy, which do not affect male fertility as severely as previous treatments.

Newly diagnosed men concerned about having children should consider sperm banking, Dr. Saxman writes. Even those who choose surveillance instead of more intensive treatments should consider sperm banking, as some 20 to 30 percent of these men will experience disease recurrence and require aggressive chemotherapy.