For the first time, Hutchinson Center scientists have identified genes that signal when oral cancer has spread to lymph nodes in the neck. If confirmed by additional research, the discovery of this four-gene set could lead to the development of a biomarker-based test of the tumor that could help physicians determine whether oral squamous cell carcinoma has spread and therefore become more deadly. The findings appear in the April 15 issue of Clinical Cancer Research.
Currently, doctors use tumor size as an indicator of potential cancer spread and remove the cervical lymph nodes of all patients whose tumors are larger than two centimeters. However, metastasis occurs in only 20 percent to 40 percent of such patients, meaning that 60 percent to 80 percent of the surgeries are unnecessary.
Fewer false positives, unnecessary surgeries
“The advantage of this gene signature, when applied to patients at risk for metastasis to neck lymph nodes, is that we’d maintain our ability to detect lymphatic metastasis while reducing the number of false positives and thus the number of unnecessary surgeries,” said corresponding author Dr. Chu Chen, a molecular epidemiologist in the Public Health Sciences Division and affiliate professor at the University of Washington.
Although patients can well tolerate neck surgery, it has the potential to cause nerve damage and create shoulder muscle problems.
The researchers found that gene expression outperforms tumor size as a predictor of metastasis in patients with no clinical evidence that their cancer has spread.
Sensitive signature detects metastasis
The study compared the effectiveness of a four-gene signature in detecting metastasis to neck lymph nodes versus tumor size alone (less than or equal to 2 centimeters vs. greater than 2 centimeters) among 59 patients with oral cancer who had no clinical evidence of metastasis to the lymph nodes.
The researchers—including the Clinical Research Division’s Dr. Eduardo Mendez and John Houck, David Doody and Drs. Pawadee Lohavanichbutr, Wenhong Fan, Lue Ping Zhao and Stephen Schwartz, all of PHS—found the use of tumor size alone resulted in many false positives. Among 49 patients with tumor size greater than two centimeters, 31 of them had negative lymph nodes in their pathology reports. Using the four-gene signature, the number of false positive was reduced to nine out of 28 patients. Moreover, the signature was sensitive enough to detect 19 of 20 lymph node-positive patients. That means that using the four-gene signature can reduce the number of unnecessary surgeries while maintain the ability to detect lymph node metastasis.
Oral squamous cell cancers include those that occur in the oral cavity, oral pharynx, tonsils and at the base of the tongue. According to the American Cancer Society, in 2010 approximately 36,540 new cases of oral cancer were diagnosed in the U.S. and 7,880 people died from the disease.
Grants from the National Cancer Institute funded the research. Investigators from the University of Washington and the University of Minnesota contributed to the study.