Most ALK rearrangements consequence from a compact inversion inside chromosome p concerning the exon within the ALK gene and distinct exons of EML , resulting in a fusion protein with constitutive activation from the ALK intracellular kinase domain. EML ALK fusion genes have a powerful oncogenic action each in vitro and in vivo and several variants are presently recognized. EML ALK translocations correlate with certain clinical and pathological characteristics, specifically lack of EGFR and K ras mutations .In addition, the presence of EML ALK fusion gene might be related with EGFR TKI resistance . We report the situation of an erlotinib resistant NSCLC patient with EGFR and ALK concomitant mutations Case report The patient was a yr previous Caucasian by no means smoker guy who, in January , was diagnosed a lung tumour in the upper right lobe with a single metastasis in the th left rib . The two lesions underwent trans thoracic fine needle aspiration that has a diagnosis of NSCLC, most steady with squamous cell carcinoma. The patient had a superb functionality standing and referred reasonable cough and left thoracic pain. No significant former healthcare historywasreported. Hence, hewastreated by using a firstline chemotherapy such as cisplatin and gemcitabine just about every 3 weeks up to 6 cycles.
The treatment method was nicely tolerated and CT and FDG PET scans evidenced a partial response inside the lung nodule which has a complete radiologic and metabolic response during the rib lesion. Offered the young age, the fantastic ROCK inhibitors efficiency status, the single metastatic web page and the favorable PET response, the patient underwent perfect upper lobectomy with lymphnode dissection and rib resection. At histology, the tumour had a prevailing part of squamous cell carcinoma with restricted parts of glandular differentiation showing luminal and intracellular mucin manufacturing . A diagnosis of poorly differentiated adenosquamous carcinoma was given. Four peribronchial lymphonodes showed metastatic deposits with histological options of solid adenocarcinoma. No rib involvement was detected. The pathological stage was pTNM and no adjuvant remedy was administered. Assessment in the EGFR standing was carried out around the lymphnode specimens by immunostaining, FISH and EGFR gene mutation evaluation.
EGFR was optimistic by immunohistochemistry in of neoplastic cells; EGFR gene amplification was also evidenced with suggest EGFR nucleus and chromosome nucleus in of tumour cells by fluorescence in situ hybridization using the LSI EGFR dual colour probe set . DNA sequencing showed a deletion of exon of EGFR gene . Just after months of stick to up, the patient referred cervical ache. The CT scan revealed lung, hepatic and bone lesions constant with ailment relapse. Looking at peptide synthesis kinase inhibitor the preceding evidence of EGFR gene mutation, the patient underwent therapy with erlotinib . In the course of erlotinib therapy, no clinical benefit was obtained and just after two months of treatment the patient died for progression of disease.