Usefulness of Cytological Samples for the Assessment of ALK Gene Rearrangements in NSCLC Patients
Tania Labiano, Jose I Echeveste, Luis M Seijo, Jose L Perez-Gracia, Alfonso Gurpide, Miguel A Idoate, Mercedes Aguirre, Isabel Zudaire, Maria D Lozano. University Clinic of Navarra, Pamplona, Spain; Center for Applied Medical Research, Pamplona, Spain
Background: ALK gene rearrangement defines a new molecular subtype of NSCLC. Crizotinib, a dual MET and ALK inhibitor, shows promising efficacy in these patients. To date, determination of EML4-ALK fusions has been performed in biopsies or surgical specimens. However, advanced lung cancer is often diagnosed in cytology specimens obtained through fine needle aspiration (FNA), and frequently cytological specimens are the only tumor samples available. We evaluated the possibility of determining ALK gene rearrangements in cytological samples from NSCLC patients.
Design: Between January and September 2011, 42 cytological samples from 42 NSCLC patients (25 M and 17 F) were analyzed for ALK gene rearrangements by FISH (Vysis dual colour break apart probe). Tumour samples were obtained by bronchoscopy guided FNA (21 cases-50%), EBUS-FNA (2 cases-4.8%), EUS-FNA (7 cases-16.7%), CT-FNA (2 cases-4.8%), and direct FNA (2cases- 4.8%). We also studied 2 cavity fluids (4.8%), 4 imprints from surgical specimens (9.5%), and 2 cellblocks received for consultation. FISH analysis was performed on Papanicolau stained smear in 15 cases (35.7%), non-stained ThinPrep in 21 cases (50%), cell block in 4 cases (9.5%), and 1 in a stained ThinPrep. All cases were previously tested for EGFR and KRAS mutations.
Results: Twenty-nine samples (69%) were adequate for FISH analysis. Two cases were positive (6.9%), both women and non-smokers of 36 and 73 yo having adenocarcinoma with signet ring cells. FISH analysis was done on ThinPrep unstained slides. One case had a concurrent EGFR mutation in exon 21. FISH study was unsuccessful in 13 cases. Ten of them were performed on Papanicolau stained smears (76.9%), and 3 on unstained ThinPrep (14.3%). All paraffin embedded samples, and 19 (86.4%) TrinpPrep were adequate for FISH analysis. Correlation between cytological and surgical samples has been performed so far in 4 cases, with a concordance rate of 100%.
Conclusions: Determination of ALK gene rearrangements in cytological specimens is feasible. ThinPrep and cell blocks are the most suitable samples for FISH analysis, while Papanicolau stained smears provide poor results. Coexistence of ALK gene rearrangement and EGFR mutation, although rare, are not mutually exclusive. Analysis by FISH of ALK gene rearrangement on ThinPrep slides could be an option when no paraffin embedded tissue is available.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 60, Monday Morning