• 10/12/2004
  • New Orleans
  • Sunil Singhal, MD et al.
  • U.S. Newswire (usnewswire.com)

Surgeons from the University of Pennsylvania, Philadephia, have isolated the genes that are expressed in head and neck cancer as well as those expressed in lung carcinoma in smokers. Armed with this information, the investigators were able to predict precisely if patients with lung masses had developed lung cancer or metastases from another source. In a study of 24 smokers from three different academic medical centers, the scientists made accurate predictions for every patient. The researchers presented their findings at the 2004 annual Clinical Congress of the American College of Surgeons (ACS).

The research group is making its genetic algorithms available to physicians throughout the world to help them decide whether an individual patient has advanced cancer that spread from the head and neck to the lung, or whether the patient has other metastatic sources that may be treated individually. Sunil Singhal, MD, a fellow in thoracic surgery, explained that smokers have a high risk for developing cancer in the head, neck, mouth, jaw, and lung. It is often difficult to identify the primary source of disease because all cancers related to smoking appear the same in tissue samples under the microscope-as squamous cell carcinoma. “People who have been smoking all their lives often have tumors in the head, in the neck, or in the tongue or jaw where the tobacco has rubbed against the inner lining of the mouth. These patients also often have masses in the chest on x-rays. There has been no way to determine whether a patient has cancer that has spread or several different cancers,” Dr. Singhal reported.

Dr. Singhal and his associates hope their genetic profiles of cancers related to smoking will become the new gold standard for determining if a patient has primary or metastatic disease. The scientists are giving the oncology community access to their genetic profiles so physicians may choose tumor- and patient- specific treatment, he said. “We are telling physicians to look at our genes or even send tissue samples to us. We’re hoping to get to the point where physicians can look on the Web, compare a patient’s genetic profile with our gold standard, and be able to immediately determine what type of cancer he or she has,” Dr. Singhal said.

The physicians are currently examining the genes that make head and neck cancer different from lung cancer so the genes may be targeted for therapy. “If we know the genetics in each tumor, we can attack that tumor specifically. Instead of giving the same, standard chemo-therapeutic regimen, we may be able to customize treatment. In the future, a doctor will take a biopsy, send it to a lab, and the lab will be able to say, ‘for this cancer, these are the best chemotherapeutic or biological agents to take based on its genetic profile’,” Dr. Singhal said.

In the study, Dr. Singhal extracted ribonucleic acid from eight smokers with lung squamous cell carcinoma and eight smokers with head and neck squamous cell carcinoma. The researchers examined more than 44,000 genes through microarray technology (genetic testing that screens thousands of genes at the same time) to find 65 genes that could distinguish lung from head and neck cancer. The goal was to develop a genomic-based classification that would identify the origin of lung squamous cell carcinoma.

After constructing statistical algorithms for each disease, the researchers prospectively classified 24 patients with an unknown primary source of head and neck or lung cancer, and they correctly identified all 17 who later were confirmed to have head and neck cancer and all seven who had lung cancer. Tissue samples from these patients were obtained from Columbia University, New York, NY; the University of Minnesota, Minneapolis, MN; and the University of Pennsylvania, Philadelphia, PA. The results were duplicated regardless of the type of micro-array platform used in the individual institutions.

Amil Vachani, MD; Michael Kupferman, MD; Charles Powell, MD, FACS; P. Gaffney, MD; Ruth Muschel, MD; Steve Albelda, MD; and Larry Kaiser, MD, FACS, also participated in the study.