Loss of PTEN Expression in Sinonasal Squamous Cell Carcinoma

Background: Squamous cell carcinoma (SCC) arising in the sinonasal and paranasal regions arises from the surface Schneiderian mucosa and may have biologically distinct molecular alterations. Identifying altered pathways for targeted therapy and markers to aid in predicting outcome and response to therapy are needed. Phosphatase and tensin homolog deleted from chromosome-10 (PTEN), a tumor suppressor gene associated with regulation of the PI3K pathway, is altered in many tumor types, including SCC in other head and neck sites. We sought to determine the incidence and potential correlation of PTEN expression with clinical parameters in sinonasal SCC.

Methods: Tumor tissue from 48 patients with primary sinonasal SCC who underwent a surgical procedure from 2001–2008 were included in a paraffin tissue microarray. Immunohistochemical analysis was performed for PTEN expression using standard techniques (PTEN 6H2.1, 1:100, Dako, Carpinteria, CA). Each tumor was evaluated for expression in duplicate cores as negative (loss of PTEN expression) or positive (staining in the cytoplasm and/or nucleus in any tumor cells).

Results: Five of 48 (10.4%) sinonasal SCC showed complete loss of PTEN expression by immunohistochemical analysis. Internal controls were positive in each case. All five tumors arose in the maxilla in three males and two females. Patients were treated with surgery with or without radiation therapy. One of the five patients developed local recurrence and was treated with salvage surgery. Three patients are alive with no evidence of disease (49–105 months follow-up), and two patients died of other causes with no evidence of disease at 33 months. Survival curves were not statistically significant between PTEN expressing tumor and those with PTEN expression loss.

Conclusions: PTEN expression is altered in a subset of sinonasal SCC with 10% showing complete loss by immunohistochemical evaluation. The significance of this alteration in sinonasal SCC is unclear, secondary to limited number of events. Studies are ongoing to delineate the molecular basis for this alteration.