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In non-small cell lung cancer (NSCLC), approximately 1-3% of cases harbor an increased gene copy number (GCN) of the MET gene. This alteration can be due to de novo amplification of the MET gene or can represent a secondary resistance mechanism in response to targeted therapies. To date, the gold standard method to evaluate the GCN of MET is fluorescence in situ hybridization (FISH). However, next-generation sequencing (NGS) is becoming more relevant to optimize therapy by revealing the mutational profile of each NSCLC. Using evaluable n = 205 NSCLC cases of a consecutive cohort, this study addressed the question of whether an amplicon based NGS assay can completely replace the FISH method regarding the classification of MET GCN status. Out of the 205 evaluable cases, only n = 9 cases (43.7%) of n = 16 high-level MET amplified cases assessed by FISH were classified as amplified by NGS. Cases harboring a MET GCN > 10 showed the best concordance when comparing FISH versus NGS (80%). This study confirms that an amplicon-based NGS assessment of the MET GCN detects high-level MET amplified cases harboring a MET GCN > 10 but fails to detect the various facets of MET gene amplification in the context of a therapy-induced resistance mechanism.

Objective: This study sought to evaluate the clinical outcome after extended sentinel lymph node dissection (eSLND) and radical retropubic prostatectomy (RRP) in patients with clinically localized prostate cancer (PCa)., Subjects and Methods: From August 2002 until February 2011, a total of 819 patients with clinically localized PCa, confirmed by biopsy, were treated with RRP plus eSLND. Biochemical recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were assessed with Kaplan-Meier curves. Various histopathological parameters were analyzed by univariate and multivariate analysis., Results: The mean follow-up was 5.3 years. Lymph node (LN) metastases occurred in 140 patients. We removed an average of 10.9 LNs via eSLND from patients with pN1 PCa. Postoperatively, 121 pN1 patients temporarily received adjuvant androgen deprivation therapy. The mean survival periods for RFS, RFS after secondary treatment, CSS, and OS were 4.7, 7.0, 8.8, and 8.1 years, respectively. The cancer-specific death rate of the 140 pN1 patients was 13.6%. RFS, CSS, and OS were significantly correlated with pathological margin status, LN density, the total diameter of evident metastases, and membership in the subgroup 'micrometastases only'., Conclusion: Despite the presence of LN metastases, patients with a low nodal tumor burden demonstrate a remarkable clinical outcome after undergoing eSLND and RRP, thus suggesting a potential curative therapeutic approach., (2014 S. Karger AG, Basel)