Lack of response to EGFR tyrosine kinase inhibitors in an amylase-producing lung cancer with a preexisting MET amplification

Abstract

A 76-year-old man was diagnosed as having lung adenocarcinoma harboring an epidermal growth factor receptor (EGFR)-activating mutation based on a transbronchial biopsy specimen. Although laboratory data showed a marked elevation of saliva-type amylase activity in both the serum and urine, the salivary glands and pancreas were not clinically involved in hyperamylasemia. The patient was treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs). However, the EGFR-TKIs were ineffective, and the patient’s amylase levels increased in parallel with disease progression. He eventually died of respiratory failure. On autopsy, the histological findings showed an invasive adenocarcinoma with micropapillary growth and an immunohistochemical study revealed the localization of the amylase in the cytoplasm of tumor cells. Using fluorescence in situ hybridization analyses of both transbronchial lung biopsy specimens obtained prior to treatment and the autopsied lung tumor, we confirmed the amplification of the MET gene prior to drug exposure. The result suggested that the lung cancer might have overcome the inhibition of EGFR-TKIs via MET amplification. This case report also indicated that the amylase levels of amylase-producing lung cancer vary with disease progression, and hyperamylasemia refractory to EGFR-TKIs may be a predictor of drug resistance to EGFR-TKIs. Therefore, if the amylase levels do not decrease sufficiently in response to EGFR-TKI treatment in patients with EGFR-mutated, amylase-producing lung cancer, the possibility that drug resistance to EGFR-TKIs may coexist with the EGFR mutation should be considered.