Molecular profiling may be useful for early diagnosis and treatment decisions for head and neck squamous cell carcinomas (HNSCC).

Head and neck cancer includes tumors of the oral cavity, oropharynx, hypopharynx, and larynx, which histopathologically are classified as squamous cell carcinomas (SCCs) in approximately 90% of all head and neck tumors.

Scientists at the University Hospital of Bonn (Germany) and their colleagues analyzed tissues from 113 patients with primary tumors, 30 recurrent tumor tissues, 85 lymph node metastases, and 20 control samples of normal squamous epithelial tissue. To determine the extent to which the mediator complex subunit 15 (MED15) levels correlated with mortality, the investigators performed immunohistochemical analysis of primary tumor tissues from the 108 patients who developed recurrent tumors.

Immunohistochemistry (IHC) staining was performed on sections of paraffin-embedded tissues using a Ventana XT immunostainer (Ventana, Tucson, AZ, USA). The investigators used various other techniques such as immunofluorescence, small interfering ribonucleic acid (siRNA) transfection. Western blot staining were detected using the ECL Plus chemiluminescence system (GE Healthcare Bio-Sciences, Pittsburgh, PA, USA).

The scientists found that found that MED15 was overexpressed in 35% of primary tumors, 30% of lymph node metastases, and 70% of recurrences, in contrast to no or low expression in control samples. They found that the mortality rate, defined as death within one to 12 years after first diagnosis, increased from 58% overall to 78% in the subset of patients whose tumors showed MED15 overexpression, with a significant association found between MED15 overexpression and high mortality.

Further investigation revealed that the mortality rate of patients with tumors in the oropharynx or oral cavity was significantly higher than that of patients with tumors in the hypopharynx or larynx. Likewise, the expression of MED15 was found to be higher in oral cavity/oropharyngeal tumors compared with tumors from the hypopharynx or larynx. Heavy alcohol consumption was found to be significantly associated with MED15 overexpression, shedding light on the possible mechanism of action of alcohol's adverse influence.

Sven Perner, MD, PhD, the lead investigator, said, “These findings regarding MED15 overexpression are particularly significant, as genetic alterations that provide cells with growth advantages and metastatic potential may be present only in subpopulations of cells in the primary tumor, but increase in tissue from metastases and relapsed HNSCC tumors.” The study was published on March 16, 2015, in the American Journal of Pathology.

Related Links:
University Hospital of Bonn 
Ventana 
GE Healthcare Bio-Sciences