Prognostic Significance of Histological Subtypes, and Calretinin, Mesothelin, p16 and p53 Expression in Pleural Malignant Mesothelioma: A Study of 311 Cases from the MESOPATH IM@EC Center.
Francoise GalateauSalle, Nolwenn Le Stang, Maria Paciencia, Carole Drougard, Veronique Abonnet, Referral Center MESOPATH IM@EC. Chu Caen, France
Background: Age, epithelioid type, T and N staging are conventional prognostic factors in pleural malignant mesothelioma [PMM] useful for the management of the patients. We aim to analyse whether histological subtyping, together with immunohistochemical markers (calretinin, mesothelin, p16, p53) can predict a better outcome.
Design: We reviewed H&E slides of 311 DPMM patients from the MESOPATH files during 1980-2008. We classified the tumors according to the WHO 2004 classification and we subclassified the epithelioid type into predominantly trabecular, predominantly papillary (either micro or macropapillary) and solid type. We also evaluated the presence of necrosis. Additionally we evaluated calretinin Zymed, mesothelin, p53 and p16 expression. A score was attributed taking account the number of cells (0 to 100%) of stained cells and the intensity of staining and were graded (1;0-24%, 2;25-74%,3;75-100%). Log Rank tests and Cox models were used to analyse the relation between histological and immunohistochemical variables and survival.
Results: There were 223 male (72%) and 88 female (28%) with an average age of 70 years old (range 28-96). Asbestos exposure was observed in 204 patients (66%). The histological type was epithelioid (n= 248, 80%), biphasic (n=27,9%), sarcomatoid (n=28, 9%) and desmoplastic (n= 8, 2%). Patients with sarcomatoid type had the worst median survival with 5 months followed by biphasic 7 months and epithelioid type 14 months. Among the 248 epithelioid type, the solid variant (n= 124, 50%) had the poorer survival with a median of 11months followed by trabecular variant 16 months(n=16, 28%), while papillary subtype (n=24, 50%) had a median survival of 24 months. Calretinin expression was higher expressed in papillary (78%, grade 3) than trabecular (67%), solid variant (56%) and sarcomatoid (32%). On univariate analysis age p=0.02, epithelioid type p<0.0001, calretinin grade 3 p<0.0001, mesothelin (p<0.0001), p53 expression(1; 0-24%, p=0.001) and p16 expression (25-100% p=0.0005) were indicators of better survival. In multivariate analysis sarcomatoid type (p=0.03)and necrosis p=0.02 were predictors of short survival.
Conclusions: Our study supports classification by histological type and subtype for epithelioid variant to better stratify survival. Evaluation of calretinin and p 16 expression are indicators of better survival by univariate analysis. In multivariate analysis sarcomatoid type and presence of necrosis favor short survival.
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 282, Tuesday Morning