ALK Rearrangements in Pancreatic Ductal Adenocarcinoma and Neuroendocrine Tumors
Rondell P Graham, Andre M Oliveira, Lizhi Zhang. Mayo Clinic, Rochester, MN
Background: ALK rearrangements were first identified in anaplastic large cell lymphomas. Subsequently, they have been observed in other malignancies, including, most recently, in pulmonary adenocarcinoma. Targeted therapy by ALK inhibitors has demonstrated efficacy in ALK-translocation positive tumors and is now a standard therapy. ALK rearrangements in pancreatic tumors including ductal adenocarcinoma and neuroendocrine tumors (NETs) have not been systematically studied before and we sought to evaluate ALK rearrangements in a large series of pancreatic tumors.
Design: Immunohistochemical expression of ALK has been shown to correlate with ALK rearrangements in tumors in other sites. Immunohistochemical stains with ALK antibody (Clone ALK1; 1:25-1:50; Dako) were performed using two tissue microarrays (TMA) to select ALK positive cases. The TMAs included 140 cases of ductal adenocarcinoma, and 46 cases of NET. The immunoreactivity was scored for each case in the microarray as 0, 1+, 2+ or 3+ using established criteria. The diagnosis of the positive TMA cases was confirmed by review of H&E-stained full sections. Thereafter, the ALK immunoreactivity was confirmed by performing the ALK immunohistochemical stain on full sections. Fluorescent in situ hybridization assay (FISH) using a break-apart assay with probes for ALK (ALK probe; Abbott, IL) was performed to detect ALK rearrangements in ALK immunohistochemistry positive cases.
Results: Of 140 ductal adenocarcinoma cases on the TMA, 5 showed immunoreactivity for ALK1 with the following degree of expression: N=1 (3+), N=2 (2+), N=2 (1+). All 46 NETs were negative. Review of H&E sections confirmed 5 adenocarcinomas including one associated with an intraductal papillary mucinous neoplasm. However, FISH for ALK locus rearrangements was negative in all five cases.
Conclusions: After screening with TMA, 5 ductal adenocarcinoma cases (3.5%) showed ALK expression, and one case showed strong immunoreactivity. However, FISH for ALK translocations was negative in all cases. Therefore, ALK expression is uncommon in pancreatic carcinomas and NETs. The rare immunohistochemical expression of the protein is not induced by ALK translocation but rather, alternative mechanisms may be responsible. These results indicate that ALK rearrangements are not a fundamental event in pancreatic tumorigenesis, and ALK is unlikely to be a major therapeutic target in pancreatic tumors.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 291, Tuesday Afternoon