192P - Prognostic biomarkers in malignant pleural mesothelioma

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Mesothelioma
Translational Research
Presenter Rosanna Mezzapelle
Citation Annals of Oncology (2014) 25 (suppl_4): iv58-iv84. 10.1093/annonc/mdu326
Authors R. Mezzapelle1, U. Miglio2, O. Rena3, F. Mercalli4, C. Veggiani4, A. Paganotti4, R. Buosi5, M. Rinaldi6, R. Boldorini4
  • 1Department Of Health Sciences, UNIVERSITY OF EASTERN PIEDMONT, 28100 - NOVARA/IT
  • 2Health Sciences, UNIVERSITY OF EASTERN PIEDMONT, 28100 - NOVRA/IT
  • 3Unit Of Thoracic Surgery, MAGGIORE DELLA CARITà HOSPITAL, 28100 - NOVARA/IT
  • 4Unit Of Pathology, MAGGIORE DELLA CARITà HOSPITAL, 28100 - NOVARA/IT
  • 5Department Of Clinical Oncology, Civil Hospital, Novara, Italy, Novara/IT
  • 6Drugs Sciences, UNIVERSITY OF EASTERN PIEDMONT, NOVARA/IT

Abstract

Aim

The standard of care for malignant pleural mesothelioma (MPM) includes combination of platinum compounds and pemetrexed. Despite this, the median survival of MPM patients is still bad (12 months). Excision Repair Cross Complementing Group 1 (ERCC1) acts removing DNA adducts formed by platinum compounds, whereas Pemetrexed inhibits Thymidylate Synthase (TS), a folic enzyme also involved in ex novo synthesis of DNA. This study aims to analyse retrospectively, in a large series of MPM specimens, the ERCC1 and TS gene and protein expression to investigate their prognostic and predictive role.

Methods

Pleural biopsies were collected from140 consecutive MPM patients (98 males and 42 females, mean age 68 years, range 27-90). Histologic subtypes were: epithelioid (#103, 73%), sarcomatoid (#19, 14%) and biphasic (#18, 13%). At the end of the study 113 patients were died (average disease specific survival (DSS) 13 months; range 1-60); mRNA was extracted from formalin fixed paraffin embedded blocks and reverse transcribed in cDNA to perform gene expression assay by qRT-PCR. Immunohistochemistry was performed by anti-ERCC1 and anti-TS mAbs and the results were scored from 0 to 3 depending on the percentage of positive tumour cells and staining intensity. The results were statistically correlated with the clinical features and with the DSS of the patients respectively by Fisher's exact test and Logrank test.

Results

Of 140 patients 102 received platinum and pemetrexed (in single or in combination), the remaining were untreated due to bad performance status, advanced age or refusing therapy. Statistically significant correlation was found between the lack of protein expression of ERCC1 and DSS in the whole cohort (P = .03). Low levels of TS mRNA were significantly correlated with the DSS in the whole cohort (P = .01) and in the untreated subgroup (including patients not receiving pemetrexed) (P = .04), whereas did not in the subgroup of pemetrexed treated patients

Conclusions

ERCC1 protein expression, scored by IHC, and TS gene expression, evaluated by mRNA analysis, seem both important prognostic markers; we suggest their evaluation in routine biopsies from patients with MPM.

Disclosure

All authors have declared no conflicts of interest.