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BackgroundBased on the excellent results of the clinical trials with ALK-inhibitors, the importance of accurately identifying ALK positive lung cancer has never been greater. However, there are increasing number of recent publications addressing discordances between FISH and IHC. The controversy is further fuelled by the different regulatory approvals. This situation prompted us to investigate two ALK IHC antibodies (using a novel ultrasensitive detection-amplification kit) and an automated ALK FISH scanning system (FDA-cleared) in a series of non-small cell lung cancer tumor samples.MethodsForty-seven ALK FISH-positive and 56 ALK FISH-negative NSCLC samples were studied. All specimens were screened for ALK expression by two IHC antibodies (clone 5A4 from Novocastra and clone D5F3 from Ventana) and for ALK rearrangement by FISH (Vysis ALK FISH break-apart kit), which was automatically captured and scored by using Bioview's automated scanning system.ResultsAll positive cases with the IHC antibodies were FISH-positive. There was only one IHC-negative case with both antibodies which showed a FISH-positive result. The overall sensitivity and specificity of the IHC in comparison with FISH were 98% and 100%, respectively.ConclusionsThe specificity of these ultrasensitive IHC assays may obviate the need for FISH confirmation in positive IHC cases. However, the likelihood of false negative IHC results strengthens the case for FISH testing, at least in some situations.

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Studies with the gemcitabine/vinorelbine (GV) or the gemcitabine/docetaxel (GD) combinations have shown similar efficacy and less toxicity compared to platinum-based chemotherapies, in patients with advanced non-small-cell lung cancer (NSCLC). The present trial was designed to test the efficacy and safety of both, GV and GD, combinations. Chemotherapy-naïve patients (n=39)or=60% and adequate hematological, renal and hepatic function were randomly assigned to receive G 1,000 mg/m2+either V 25 mg/m2 or D 35 mg/m2 (all of which were administered i.v.) on days 1 and 8 every 21 days. Baseline characteristics were comparable in GV (n=20) and GD (n=19) groups. Results indicated objective response of 7 (35%) vs 6 (31%) patients and median time-to-treatment failure of 120 versus 90 days in the GV and GD arms, respectively. The most common non-hematological toxicities were (GV vs GD): grade 2-4 pulmonary toxicity in 1 (5%) vs 7 (37%); grade 2-3 diarrhea 0 versus 4 (21%) and edema 1 (5%) vs 3 (16%); grade 3-4 hematological toxicities occurred in 3 (15%) vs 1 (5%) patients. Our results indicate that the combination of gemcitabine/docetaxel does not have a favorable safety profile with this schedule of administration, particularly in terms of pulmonary toxicity.

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