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Also in the December 21 Journal of the National Cancer Institute

Journal of the National Cancer Institute

Two Studies Look at Methods for Studying Biomarkers
In the future, biomarkers may be used as early markers of cancer and to predict a patient's response to therapy and overall chance of survival. Two studies in the December 21 issue of the Journal of the National Cancer Institute address methodologic issues that surface when studying biomarkers.

The concentration of biomarker antibodies, antibodies against proteins that scientists use to measure the progression of a disease, can affect what a certain level of protein expression indicates about patient survival.

David L. Rimm, M.D., Ph.D., a member of Yale Cancer Center at Yale University School of Medicine and colleagues used tissue microarray analysis and a range of antibody concentrations to test the expression of HER2, p53, and the estrogen receptor (ER) proteins in tissue samples from tumors from 250 breast cancer patients.

When the authors used a high concentration of antibodies and an optimal range of data, low expression of HER2 and p53 proteins was associated with low patient survival. Alternately, when researchers used a low concentration of antibodies and an optimal range of data, high expression of HER2 and p53 proteins was associated with low patient survival. Rimm and colleagues suggest that biomarker antibody concentration appears to affect the relationship between biomarker expression and outcome in analyses measuring expression by use of a method used for quantitative analysis of protein expression, called AQUA.

In an accompanying editorial, Donald Earl Henson, M.D., of the George Washington University Cancer Institute in Washington, D.C., writes that the results from Rimm and colleagues "warrant consideration." He suggests that additional studies are required that use alternate antibodies, detection methods, and biomarkers.

In a second study, Gabriella Sozzi, Ph.D., at the Istituto Nazionale per lo Studio e la Cura dei Tumori in Milan, Italy, and colleagues examined the effect of long-term storage of plasma and isolated plasma DNA on the amount of free circulating DNA that can be measured. Levels of free circulating DNA have been investigated as a possible biomarker for lung cancer.

Sozzi and colleagues found that levels of circulating DNA declined about 30% after each year of storage. They suggest such observations should be taken into account when scientists use stored samples for data analysis.

Contacts:
Article (Rimm): Renee E. Gaudette, Associate Director, Public Affairs and Marketing, Yale Cancer Center, 203-785-2143, renee.gaudette@yale.edu

Editorial: Donald Earl Henson, George Washington University School of Medicine, patdeh@gwumc.edu

Article (Sozzi): Gabriella Sozzi, Istituto Nazionale per lo Studio e la Cura dei Tumori, 39-02-23902232-2643, Gabriella.sozzi@istitutotumori.mi.it

Study Examines Origins of Secondary Lesions in Female Genital Tract
High-grade cervical dysplasia and subsequent genital lesions may originate from the same group of abnormal cells, according to a new study.

Infection with high-risk human papillomavirus (HPV), which integrates into the host DNA at random sites, can cause cervical cancer in women. It is unknown whether subsequent genital lesions and cancers arise from new HPV infections or whether they come from the same transformed cell population as the original cancer. To address this question, Magnus von Knebel Doeberitz, M.D., at the University of Heidelberg in Germany, and colleagues studied DNA isolated from tumor tissue samples of seven patients who had developed vaginal cancers after treatment for cervical cancer.

They found that tumors occurring along the female genital tract in patients infected with high-risk HPV contained HPV integration sites that had identical HPV DNA to those in the earlier cervical tumors. The authors conclude that high-grade cancerous lesions in the female genital tract share a common origin with initial cervical tumors and may come from transformed cells derived from the uterine cervix.

In an accompanying editorial, Qinghua Feng, Ph.D., and Nancy B. Kiviat, M.D., of the University of Washington in Seattle, discuss the possibility that some vaginal tumors might come from cells from cervical cancers. Feng and Kiviat suggest that the surgery used to remove the cervical cancer might harm the vaginal epithelium and make the tissue more likely to accept cancerous cells.

Contacts:
Article: Annette Tuffs, Leiterin der Pressestelle, 06221-56-45-36, Annette_Tuffs@med.uni-heidelberg.de
Editorial: Nancy B. Kiviat, University of Washington, nbk@u.washington.edu

CXCR4 Expression Associated with Decreased Survival in Esophageal Cancer
Expression of CXCR4, a receptor that helps cells home in on bone marrow and sites of inflammation, is associated with poor survival in esophageal cancer patients and may play a role in the metastatic spread of tumor cells, according to a study by Jussuf T. Kaifi, M.D., Klaus Pantel, M.D., and Jakob R. Izbicki, M.D., of the Universitaetsklinikum Hamburg-Eppendorf in Hamburg, Germany, and colleagues.

Kaifi and colleagues obtained tumor tissue samples from 136 patients who underwent surgery for esophageal cancer. They found that CXCR4 expression in tumor tissues was associated with tumor cell spread into the lymph nodes and bone marrow. In addition, CXCR4 expression was associated with lower survival rates, and the authors suggest that the receptor could be involved in early metastasis.

Contact: Mathias Goyen, Universitaetsklinikum Hamburg-Eppendorf, 49-040-42803-6071, goyen@uke.uni-hamburg.de

Also in the December 21 JNCI:

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