Abstract

Background: Na/H exchange regulator factor 1 (NHERF1/EBP50) isan adaptor/signaling protein that when aberrantly expressed has been associated with tumor development and progression. In some tumors this occurs through its interaction with the PIK3-PTEN-AKT pathway.

Objective: This study explores NHERF1 biomarker expression in lung cancers and, further, NHERF1 and PTEN expression and the PIK3CA-PTEN-AKT pathway in squamous cell lung carcinoma (SQCC).

Design: Phase 1: The immunohistochemical expression of NHERF1 was examined in a lung cancer microarray and correlated with histologic type of tumor and stage. Phase 2: NHERF1 and PTEN expression in 21 SQCC was correlated. Mutations in the PIK3CA/PTEN/AKT pathway were analyzed by NGS.

Results and conclusions: Phase 1: NHERF1 expression and histologic subtype strongly correlated (p<0.001). Small cell carcinomas were negative. SQCCs exhibited moderate to strong expression. Strong aberrant expression in adenocarcinomas correlated with lymph node metastases (p=0.005). Phase 2: 20 SQCC cases expressed NHERF1. PTEN was negative in 7 cases, heterogeneous in 2, and positive in 13. There was no correlation between NHERF1 and PTEN expression, arguing against cooperativity of the proteins in this setting. AKT, PTEN, and PIK3CA did not have detectable mutations. PTEN loss was not associated with an underlying genetic mutation, suggesting a different mechanism for deregulation.

Keywords: Lung cancer, NHERF1, PIK3CA-PTEN-AKT pathway