title: Ki67 index is an independent prognostic factor in epithelioid but not in non-epithelioid malignant pleural mesothelioma: a multicenter study.
abstract: BACKGROUND
  Estimating the prognosis in malignant pleural mesothelioma (MPM) remains challenging. Thus, the prognostic relevance of Ki67 was studied in MPM.
  
  
  METHODS
  Ki67 index was determined in a test cohort of 187 cases from three centres. The percentage of Ki67-positive tumour cells was correlated with clinical variables and overall survival (OS). The prognostic power of Ki67 index was compared with other prognostic factors and re-evaluated in an independent cohort (n=98).
  
  
  RESULTS
  Patients with Ki67 higher than median (>15%) had significantly (P<0.001) shorter median OS (7.5 months) than those with low Ki67 (19.1 months). After multivariate survival analyses, Ki67 proved to be-beside histology and treatment-an independent prognostic marker in MPM (hazard ratio (HR): 2.1, P<0.001). Interestingly, Ki67 was prognostic exclusively in epithelioid (P<0.001) but not in non-epithelioid subtype. Furthermore, Ki67 index was significantly lower in post-chemotherapy samples when compared with chemo-naive cases. The prognostic power was comparable to other recently published prognostic factors (CRP, fibrinogen, neutrophil-to-leukocyte ratio (NLR) and nuclear grading score) and was recapitulated in the validation cohort (P=0.048).
  
  
  CONCLUSIONS
  This multicentre study demonstrates that Ki67 is an independent and reproducible prognostic factor in epithelioid but not in non-epithelioid MPM and suggests that induction chemotherapy decreases the proliferative capacity of MPM.
authors: 1] Department of Surgery, Comprehensive Cancer Center, Division of Thoracic Surgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria [2] Institute of Cancer Research and Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria.
authors: B
authors: B
authors: Ghanim
authors: Department of Surgery, Comprehensive Cancer Center, Division of Thoracic Surgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors: T
authors: T
authors: Klikovits
authors: 1] Department of Surgery, Comprehensive Cancer Center, Division of Thoracic Surgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria [2] Institute of Cancer Research and Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria.
authors: M A
authors: MA
authors: Hoda
authors: 1] Department of Surgery, Comprehensive Cancer Center, Division of Thoracic Surgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria [2] Department of Thoracic Surgery, Semmelweis University, 1085 Budapest, Hungary.
authors: G
authors: G
authors: Lang
authors: 2nd Institute of Pathology, Semmelweis University, 1085 Budapest, Hungary.
authors: I
authors: I
authors: Szirtes
authors: Division of Pathology, Otto Wagner Hospital, 1145 Vienna Austria.
authors: U
authors: U
authors: Setinek
authors: 1] Department of Surgery, Comprehensive Cancer Center, Division of Thoracic Surgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria [2] National Koranyi Institute of TB and Pulmonology, 1121 Budapest, Hungary.
authors: A
authors: A
authors: Rozsas
authors: 1] Department of Surgery, Comprehensive Cancer Center, Division of Thoracic Surgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria [2] National Institute of Oncology, 1525 Budapest, Hungary.
authors: F
authors: F
authors: Renyi-Vamos
authors: Department of Surgery, Comprehensive Cancer Center, Division of Thoracic Surgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors: V
authors: V
authors: Laszlo
authors: Institute of Cancer Research and Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria.
authors: M
authors: M
authors: Grusch
authors: Institute of Cancer Research and Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria.
authors: M
authors: M
authors: Filipits
authors: Department of Surgery, Comprehensive Cancer Center, Division of Thoracic Surgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors: A
authors: A
authors: Scheed
authors: Department for Respiratory Diseases Jordanovac, School of Medicine, University of Zagreb, University Hospital Center, 10 000 Zagreb, Croatia.
authors: M
authors: M
authors: Jakopovic
authors: Department for Respiratory Diseases Jordanovac, School of Medicine, University of Zagreb, University Hospital Center, 10 000 Zagreb, Croatia.
authors: M
authors: M
authors: Samarzija
authors: Institute of Pathology, School of Medicine, University of Zagreb, 10 000 Zagreb, Croatia.
authors: L
authors: L
authors: Brcic
authors: Department of Thoracic Surgery, University of Zagreb, 10 000 Zagreb, Croatia.
authors: D
authors: D
authors: Stancic-Rokotov
authors: University Clinic of Respiratory and Allergic Diseases, 4204 Golnik, Slovenia.
authors: I
authors: I
authors: Kern
authors: University Clinic of Respiratory and Allergic Diseases, 4204 Golnik, Slovenia.
authors: A
authors: A
authors: Rozman
authors: Department of Pathology, Medical University of Vienna, 1090 Vienna, Austria.
authors: G
authors: G
authors: Dekan
authors: Department of Surgery, Comprehensive Cancer Center, Division of Thoracic Surgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors: W
authors: W
authors: Klepetko
authors: Institute of Cancer Research and Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria.
authors: W
authors: W
authors: Berger
authors: 1] 2nd Institute of Pathology, Semmelweis University, 1085 Budapest, Hungary [2] National Koranyi Institute of TB and Pulmonology, 1121 Budapest, Hungary.
authors: T
authors: T
authors: Glasz
authors: 1] Department of Surgery, Comprehensive Cancer Center, Division of Thoracic Surgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria [2] Department of Thoracic Surgery, Semmelweis University, 1085 Budapest, Hungary [3] National Koranyi Institute of TB and Pulmonology, 1121 Budapest, Hungary [4] National Institute of Oncology, 1525 Budapest, Hungary.
authors: B
authors: B
authors: Dome
authors: 1] Department of Surgery, Comprehensive Cancer Center, Division of Thoracic Surgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria [2] MTA-SE Molecular Oncology Research Group, Hungarian Academy of Sciences, 1091 Budapest, Hungary.
authors: B
authors: B
authors: Hegedus
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015622:Epithelioid Cells / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D010997:Pleural Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D019394:Ki-67 Antigen
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