ALK chromosomal alterations in neuroendocrine tumors.

Abstract

10585 Background: Neuroendocrine tumors (NETs) comprise a heterogeneous group of neoplasms containing biologically active peptides and amines in their cytoplasm. Anaplastic lymphoma kinase (ALK) translocation has recently emerged as a potent predictor of benefit for treatment with ALK inhibitors. The endpoint of this study was to analyze ALK translocations and gene copy number status in a series of neuroendocrine tumors and correlate these findings with clinico-pathological features. Methods: Paraffin-embedded specimens from gastroenteropancreatic (GEP) and lung neuroendocrine tumors from patients diagnosed between years 2004-2010 were retrospectively retrieved from the tumor bank at our Institution. ALK gene status was characterized by fluorescence in situ hybridization (FISH) with a break-apart ALK probe (Abbot Molecular Inc). Translocation and gene copy gain were defined as previously reported (Salido et al). FISH ALK-positive and a set of negative cases were evaluated by immunohistochemistry (ALK-1, Dako). Statistical analysis was carried to evaluate the association between ALK gene alterations and clinico-pathological features. This study was approved by the review board at our Institution. Results: One hundred and eleven neuroendocrine tumors were included in the study. In 42 cases the sample was insufficient/inconclusive FISH results, leaving a final number of 69 evaluable cases (43 GEP, 20 lung, 6 other). There was one GEP neuroendocrine tumor (appendix) with an EML4-ALK translocation in 15% of tumoral cells and one lung neuroendocrine tumor with an atypical ALK translocation in 60% of tumoral cells (unknown partner). Ten cases (7 GEP; 3 lung) showed an increase in ALK gene copy number (mean 5 copies; range: 3-10 copies) with the percentage of cells with ALK copy gain ranging between 18-65% (mean 36%). Immunohistochemistry revealed <10% of tumor cells with mild ALK staining in the specimen with EML4-ALK translocation. The low number of positive cases precluded the finding of statistical associations. Conclusions: Although rare, ALK translocations are present in neuroendocrine tumors. This reveals a potential new indication for ALK inhibitors that merits further investigation.