Expression of IMP3 and Deletion of p16 Are Diagnostic and Prognostic Biomarkers in Mesothelial Proliferations
Marie Karanian, Nolwenn Le Stang, Francoise Galateau Salle. CHU Caen Cote De Nacre, Caen, France
Background: IMP3 is an oncofetal protein known as sensitive and specific marker of malignancies. Few studies were available about IMP3 expression in mesothelial proliferations. P16 deletion is one of the most common molecular abnormalities in malignant mesothelioma. First aim was to confirm the utility of IMP3 to distinguish benign from malignant mesothelial proliferations, alone or in association with p16 deletion. Second aim was to study IMP3 expression in a spectrum of mesothelial pathology.
Design: IMP3 expression was studied by immunochemistry (dako) and p16 deletion was studied by Fluorescence in situ hybridization (vysis) in 35 epithelioïd mesothelioma (EM), 26 mesothelioma in situ (MIS), 37 atypical mesothelial proliferations (AMP) and 20 reactive mesothelial proliferations (RPM). Expression of IMP3 was considered positive when more than 10% tumor cells showed cytoplasmic staining. Intensity staining was graded as very weak, weak to moderate, moderate to strong and strong. P16 was deleted when more than 50% tumor cells showed 1 allelic probe and 2 centromeric probes. Fischer exact test and log rank test were used.
Results: IMP3 expression was significantly more frequent in EM (24, 65%) and in MIS than in AMP (11, 29%) and RMP (0%) (p=0,0015). IMP3 staining was significantly stronger in EM (21, 60%) and MIS (16, 62%) than in AMP (6, 16%) (p>0,0001). P16 deletion was more frequent in EM (18, 51%) and MIS (12, 46%) than in AMP (6, 17%) and RPM (0%). IMP3 expression was mostly observed in cases with p16 deletion (29, 81%) than in cases without deletion (23,29%) (p=0,001). Survival was significantly decreased in IMP3 positive cases (14 versus 55 months, p<0,001), in cases with a strong IMP3 staining (11 versus 55 months, p>0,001) and finally in cases with a deletion of p16 (14 versus 40 months, p<0,0001). IMP3 was more sensitive (67%) than p16 deletion (50%), both were very specific (100%) for mesothelioma. Using 2 tests concomitantly increase the sensitivity (75%). IMP3 staining was heterogeneous in 31 (59%) that can be a limit in small biopsies.
Conclusions: To our knowledge, this is the first time that IMP3 appears as a prognostic marker in mesothelioma. For the diagnosis of mesothelioma versus reactive mesothelial proliferation, IMP3 expression is more sensitive than p16 deletion and highly specific.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 280, Wednesday Afternoon