دانلود رایگان ترجمه مقاله تغییر بافت شناسی موتانت EGFR آدنوکارسینوم ریه – الزویر 2017

تغییر بافت شناسی موتانت EGFR آدنوکارسینوم ریه بدون قرار گرفتن در معرض مهار EGFR

Histologic transformation of EGFR mutant lung adenocarcinoma without exposure to EGFR inhibition

Abstract

Resistance to EGFR kinase inhibitors appears to be invariable in the treatment of non-small cell lung cancer. Several mechanisms have been described. Here, we report the first case of histologic transformation of EGFR mutant lung adenocarcinoma without prior exposure to EGFR inhibition

1- Introduction

Despite initial marked response to EGFR kinase inhibitors in patients with non-small cell lung cancer (NSCLC) harboring activating EGFR mutations, drug resistance develops within a median of 12 months. Described resistance mechanisms include secondary mutations within EGFR (e.g. T790M), MET amplification, PI3K pathway hyperactivation, HER2 amplification, AXL overexpression, and epithelial-to-mesenchymal transition. Additionally, in rare cases, EGFR mutant lung adenocarcinoma may undergo histologic transformation to small cell lung cancer and squamous cell cancer after EGFR inhibitor treatment [1,2]. Here, we report the first case of histologic transformation of EGFR mutant lung adenocarcinoma without prior exposure to EGFR inhibition.

2- Case report

During radiographic evaluation of a stage 3A invasive ductal carcinoma of the right breast, a 79-year old woman with no smoking history was found to have a right middle lobe mass (Fig. 1A). Biopsy demonstrated a TTF-1- and Napsin A-positive primary lung adenocarcinoma (Fig. 2A–C) harboring a classic EGFR exon 19 deletion (Fig. 3). She underwent right middle lobe lobectomy and mediastinoscopy, with a final diagnosis of stage 2 (T2N1M0) disease. The patient received three cycles of adjuvant carboplatin-pemetrexed chemotherapy (Fig. 1C). Subsequently she underwent partial right mastectomy, breast and axillary radiation therapy, and started tamoxifen. Approximately 13 months after completing adjuvant chemotherapy, surveillance chest CT demonstrated an enlarging nodule at the right cardiophrenic angle (Fig. 1D). Biopsy revealed squamous cell carcinoma (Fig. 2E–F) with no evidence of adenocarcinoma histology. Molecular analysis demonstrated the original EGFR exon 19 deletion and no evidence of T790M mutation (Fig. 3). Immunohistochemical analysis of both the original and subsequent lung tumors demonstrated Rb expression (images not shown), suggesting absence of small cell histology. For both the original and subsequent lung tumors, all available tissue underwent histologic review. The patient initiated erlotinib, with partial response lasting six months (Fig. 1E)