amplification assessed using optimized FISH reporting criteria predicts early distant metastasis in patients with non-small cell lung cancer.

To investigate the prognostic impact of copy number (-CN) in patients with non-small cell lung cancer (NSCLC), we retrospectively reviewed clinical and pathologic data of NSCLC patients whose tumors were assessed for -CN using fluorescence hybridization (FISH). We correlated -CN status with patient overall survival (OS) and optimized -FISH reporting criteria. The study group included 384 patients with NSCLC of which 88% were adenocarcinoma and 55.7% of patients had distant metastases. There were 170 patients with stages I-III and 214 patients with stage IV disease. Based on the -CN and /CEP7 ratio the patients were classified into 3 categories: -amplification (amp): /CEP7 ≥ 2 or -CN ≥ 5; -CN-gain (cng): -CN ≥ 4 to < 5; and -negative (neg): -CN < 4. amp was associated with high fatality (=.036) and stage IV tumors (=.038). In patients with stages I-III NSCLC, patients in the amp category had the shortest OS (=.015) and more often developed distant metastases within 1 year (=.004). In patients with stage IV tumors, amp did not further impact the OS. Patients in the cng category had the longest OS (=.053). Multivariate analysis confirmed amp to be an independent high-risk factor (HR 3.26; =.026) and predicted earlier progression to distant metastasis (HR 4.86; =.001). In conclusion, we suggest that the -FISH criteria presented optimizes risk stratification by defining 3 categories of NSCLC patients. amp is an independent risk factor predicting early distant metastasis and patients with cng could represent a lower-risk group.