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Gene expression signature may prevent undetected metastases in OSCC
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The combination of clinical assessment and a gene expression signature cut undetected nodal metastases in half in a cohort of patients with early-stage oral cancers, according to study results.
The researchers aimed to validate a gene expression signature that can help distinguish between metastasizing and non-metastasizing squamous cell carcinoma of the oral cavity (OSCC) and oropharynx. The signature has been found to be a prognostic factor in these two diseases. Misdiagnosis of the likelihood of metastasis previously has led to over-treatment.
Sander R. van Hooff
The current analysis included 94 samples that had been evaluated using generic, whole-genome DNA microarrays. The researchers transferred signature genes to a dedicated microarray, and then analyzed 222 addition samples from patients with head and neck cancersusing the same technology. They used polymerase chain reaction to determine HPV status.
Researchers observed a negative predictive value of 72% for the diagnostic signature in the validation cohort of 222 samples.
The signature was associated with a negative predictive value of 89% on a subset of 101 early-stage (cT1-T2N0) oropharynx samples.
“Combining current clinical assessment with the expression signature would decrease the rate of undetected nodal metastases from 28% to 11% in early-stage OSCC,” the researchers wrote. “This should be sufficient to enable clinicians to refrain from elective neck treatment.”
In an accompanying editorial, Edmund A. Mroz, MD, and James W. Rocco, MD, PhD, both of Massachusetts General Hospital in Boston, highlighted the large number of diagnostic genes that were used quantitatively in the study.
“The risk of nodal metastasis for each patient was gauged by how closely each of its 732 expression values matched the corresponding average expression value over the 54pN+ patients in the ‘platform transition’ cohort,” Mroz and Rocco wrote. “This type of signature avoids the risk of relying on a small set of genes or on yes/no categorization of expression.”
The large number may provide more reliability from study to study, Mroz and Rocco wrote. However, they noted that the clinical community now must translate microarray analysis into clinical practice.
“Even if future prospective studies support the present estimates of assay performance, and even if the practical difficulties of disseminating this technology widely can be overcome, there are significant clinical issues with regard to whether or how patients and physicians should use this information in the way that these authors propose,” they wrote.
Some of the issues that could be problematic include changes in the timing of the course of care to wait for microarray results; the low specificity of microarray-based classification; the risk that true metastasizing patients who are misclassified may experience a delayed diagnosis during watchful waiting; and the possibility that patients correctly classified as non-metastasizing may have difficulty handling the uncertainty of watchful waiting.
“The types of tradeoffs would be changed under the approach these authors propose, but much uncertainty would remain,” Mroz and Rocco wrote.
For more information:
Mroz EA. J Clin Oncol; 2012;doi:10.1200/JCO.2012.44.8050.
van Hooff SR. J Clin Oncol. 2012;doi:10.1200/JCO.2011.40.4509.
Disclosure: See study for disclosure information. Mroz and Rocco report no relevant financial disclosures.