We are especially grateful to M. Angeles Ros Roca for technical assistance. We thank Rosario Martinez and all the Biobank p38 kinase assay personnel for their help. We are also grateful to our laboratory members for helpful comments. Conflicts of interest: The authors declare no conflict of interest. “
“High mortality rate of non–small cell lung cancer (NSCLC) patients after a curative surgery [1] suggests that the tumor-node-metastasis (TNM) staging system is insufficient for patient’s prognosis and therapeutic decisions and that new prognostic factors are needed [2]. Aberrations of MET proto-oncogene, frequently observed in cancer [3] and [4], are one of the molecular factors with
a possible prognostic potential [5]. An association between MET copy gains and a worse prognosis in patients with NSCLC has been found previously [6], [7], [8] and [9], but the data are limited and inconsistent. Recently, an increase in MET copy number (CN) has been demonstrated to be responsible for about 20% cases of the acquired Doxorubicin research buy resistance to EGFR tyrosine kinase inhibitors (TKIs) in patients with NSCLC [10] and [11], suggesting that, as a pre-existing condition occurring before treatment, it may provide a primary lack of response [12], although a number
of researchers deny that possibility [10] and [13]. The rate of MET copy gain in NSCLC reported thus far ranges significantly from 3% to 21% depending on the detection technique used [6], [7], [14], [15], [16] and [17] and patient cohort differences [15]. Moreover, although a few studies examined the association dipyridamole between MET CN alterations and protein level in cancers [16], [17] and [18],
no data regarding MET mRNA expression in lung cancer are available. The aim of the present study was to evaluate MET CN and mRNA expression level in stage I to IIIA NSCLC tumor samples and to assess their associations with clinicopathologic characteristics of the patients including the postoperative outcome. In addition, the relations between the mutational status of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and KRAS genes and MET CN alterations were analyzed. The study was performed on pairs of freshly frozen cancerous and unaffected lung tissue specimens obtained from patients with NSCLC stage I to IIIA (pTNM, 7th edition, 2009) who underwent a curative surgery at the Bialystok Medical University Hospital between 2003 and May 2010 and were followed-up for at least 3 years. None of the patients received chemotherapy or radiotherapy before the surgery. Tissue samples were collected intraoperatively and processed immediately after surgical resection: After the macroscopic visual assessment, the tumors were divided into two sections. One of them was fixed in formalin followed by paraffin embedding and the other, as well as the unaffected lung tissue specimen from the same lobe or lung of the patient, was frozen in liquid nitrogen followed by storage at − 80°C.