Fluorescence In Situ Hybridization (FISH)-Assessed Amplification of Anaplastic Lymphoma Kinase (ALK) Gene Is Detectable in a Subset of Pulmonary Sarcomatoid Carcinomas (PSC)
Giuseppe Pelosi, Patrizia Gasparini, Gabriella Sozzi, Roberto Caserini, Alberto Cavazza, Giulio Rossi, Mauro Papotti, Ugo Pastorino, Paolo Scanagatta, Massimo Barberis, Yukio Nakatani. National Cancer Institute and University of Milan School of Medicine, Milan, Italy; National Cancer Institute, Milan, Italy; Arcispedale Santa Maria Nuova, Reggio Emilia, Italy; Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy; University of Turin, Turin, Italy; European Institute of Oncology, Milan, Italy; Chiba University Graduate School of Medicine, Chiba, Japan
Background: The prevalence of ALK gene alterations for targeted therapy with specific inhibitors is a largely unexplored issue in pulmonary sarcomatoid carcinoma (PSC), a life-threatening tumor subset whose treatment still is disappointing.
Design: ALK gene status by fluorescence in situ hybridization (FISH) and protein expression by immunohistochemistry (IHC) were performed on formalin-fixed, paraffin-embedded material from 34 PSC, including 30 pleomorphic carcinomas (PLC), two pulmonary blastomas (PB) and two carcinosarcomas (CS). Fifty-one consecutive metastatic lung adenocarcinomas (MELAD) were also assessed in parallel for ALK with both FISH and IHC. The occurrence of ALK gene rearrangement and amplification was evaluated according to widely agreed-upon criteria on at least 100 tumor cells.
Results: While no rearrangements of ALK gene were detected in PSC, relevant amplification was identified in 6/34 (18%) PLC (1 female and 5 males, all smokers, aged 63 to 75 years), but not in PB or CS. The percentage of amplified tumor cells ranged from 11% to 43%, with a mean gene copy gain (GCG) ± standard deviation (SD) of 7.5±1.5. No differences in GCG (±SD) were seen in amplified tumors between the epithelial (7.4±1.5) and the sarcoma-like (7.7±1.6) components, suggesting an early engagement of ALK amplification during tumor progression of a common ancestor lesion. In the remaining 28 non-amplified PSC, the relevant GCG±SD for ALK was 3.4±0.9 with a percentage of involved tumor cells ranging from 19% to 92% (p=0.0002). Out of 51 MELAD used as controls, 10 showed ALK rearrangement (p=0.012) with no differences in gender and age distribution, whereas only one case exhibited amplification (p=0.015). ALK protein IHC was found in rearranged MELAD, but not in amplified PLC.
Conclusions: ALK gene amplification clustered into a significant subset of elderly, smoking, predominantly male PLC patients, revealing significant differences with lung adenocarcinoma. ALK amplification was not associated with protein accumulation when assessed by IHC. Response to therapy of ALK amplification in these tumors is at present unknown and clinical studies are clearly warranted.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 307, Tuesday Morning