title: Calretinin but not caveolin-1 correlates with tumour histology and survival in malignant mesothelioma.
abstract: Malignant mesothelioma (MM) continues to be a disease with poor prognosis and limited treatment options. Calretinin and caveolin-1 expression by tumour in MM have recently been described to be associated with tumour histology, differentiation and consequently survival. In a large, well annotated cohort, we studied both of these biomarkers and explored their association with clinicopathological parameters and survival. A retrospective search of patients with MM who underwent surgery at the Austin Hospital in Melbourne, Australia, was conducted. Clinical history and outcome data were retrieved from patient records. Tissue microarrays (TMAs) were constructed and stained for calretinin and caveolin-1. 'H scores' were derived, taking intensity and distribution of staining, and the cohort was dichotomised using median values for both markers. In the 329 patients evaluated, median age was 67 years. Males outnumbered females by 5:1. Epithelioid histology 202/319 (62.9%) was the most common, followed by biphasic 72/319 (21.8%) and sarcomatoid 45/319 (13.6%); histology could not be confirmed in 10 patients. Calretinin expression was detected in 246 of the 324 (76%) evaluable patients and high expression was associated with epithelioid histology (p < 0.0001). Caveolin-1 was expressed in 298 (94%) of 317 evaluable patients which was much higher compared to its expression in a cohort of lung adenocarcinomas (8/58, 13.7%). However, no association with histology was found (p = 0.409). When taken as a continuous variable, calretinin expression was found to be an independent predictor of survival, alongside histology, neutrophil-lymphocyte ratio, weight loss and stage. No prognostic value was demonstrable for caveolin-1 expression and calretinin/caveolin-1 ratio. There was no relationship between calretinin and caveolin-1 expression. In MM, increased calretinin expression is associated with epithelioid histology and better survival. Caveolin-1 is a sensitive MM marker and is expressed in a high proportion of cases but lacks association with histology and survival.
authors: Department of Medicine, University of Melbourne, Vic, Australia; Olivia Newton John Cancer Research Institute, Vic, Australia.
authors: Bibhusal
authors: B
authors: Thapa
authors: Olivia Newton John Cancer Research Institute, Vic, Australia.
authors: Marzena
authors: M
authors: Walkiewicz
authors: Olivia Newton John Cancer Research Institute, Vic, Australia; Department of Pathology, Austin Health, Vic, Australia.
authors: Carmel
authors: C
authors: Murone
authors: Department of Pathology, Austin Health, Vic, Australia.
authors: Khashayar
authors: K
authors: Asadi
authors: Olivia Newton John Cancer Research Institute, Vic, Australia; Anatpath, Gardenvale, Vic, Australia.
authors: Siddhartha
authors: S
authors: Deb
authors: Department of Thoracic Surgery, Austin Hospital, Melbourne, Vic, Australia.
authors: Stephen
authors: S
authors: Barnett
authors: Department of Thoracic Surgery, Austin Hospital, Melbourne, Vic, Australia.
authors: Simon
authors: S
authors: Knight
authors: Department of Medical Oncology, Austin Health, Olivia-Newton John Cancer and Wellness Centre, Vic, Australia.
authors: Paul
authors: P
authors: Mitchell
authors: Department of Epidemiology and Preventive Medicine, Monash University, Vic, Australia.
authors: Danny
authors: D
authors: Liew
authors: Garvan Institute of Medical Research, NSW, Australia.
authors: D Neil
authors: DN
authors: Watkins
authors: Olivia Newton John Cancer Research Institute, Vic, Australia; Department of Medical Oncology, Austin Health, Olivia-Newton John Cancer and Wellness Centre, Vic, Australia; School of Cancer Medicine, La Trobe University, Vic, Australia. Electronic address: tom.john@onjcri.org.au.
authors: Thomas
authors: T
authors: John
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D064032:Calbindin 2 / Q000032:analysis / Q000096:biosynthesis*; D051242:Caveolin 1 / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology*; D008297:Male; D008654:Mesothelioma / Q000401:mortality / Q000473:pathology*; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D010997:Pleural Neoplasms / Q000401:mortality / Q000473:pathology*; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; C576764:CALB2 protein, human; C495540:CAV1 protein, human; D064032:Calbindin 2; D051242:Caveolin 1
keywords: Calretinin; caveolin-1; immunohistochemistry; mesothelioma