Clinical implications of novel activating EGFR mutations in malignant peritoneal mesothelioma

World Journal of Surgical Oncology

Research

Swapan K Nath¹  Poonam Sharma²  Zoran Gatalica²  Joseph H Carreau³  Brian W Loggie³  Uppala Radhakrishna³  Venkatesh Govindarajan³  Jason M Foster⁴ 

[1] Department of Arthritis and Immunology, Oklahoma University, Oklahoma City, OK, USA;Department of Pathology, Creighton University Medical Center, N 30th St., 601, Omaha, NE, USA;Department of Surgery, Creighton Cancer Center, Creighton University, Omaha, NE, USA;Department of Surgery, Creighton Cancer Center, Creighton University, Omaha, NE, USA;Department of Surgery, University of Nebraska Medical Center, Omaha, NE, USA;

关键词: Epidermal Growth Factor Receptor;    Erlotinib;    Epidermal Growth Factor Receptor Mutation;    Malignant Mesothelioma;    Epidermal Growth Factor Receptor Inhibitor;   

DOI  :  10.1186/1477-7819-8-88

 received in 2010-05-03, accepted in 2010-10-13,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundThere is a paucity of information about the molecular perturbations involved in MPM tumor formation. We previously reported that EGFR-TK mutations in MPM were predictive of achieving optimal surgical cytoreduction, but the status of EGFR pathway activation potential of these mutations was not known. Here we present the mutant EGFR activating potential and the matured survival data of the EGFR mutant(mut+) relative to wild type EGFR(mut-) mesothelioma.MethodsTwenty-nine patients were evaluated and their tumors were probed for mutations in the catalytic TK-domain. Twenty-five patients were treated with cytoreductive surgery and complete clinical data was available for comparison of the mut+ and mut- groups. A COS-7 cell expression model was used to determine mutation activating profiles and response to erlotinib.ResultsFunctional mutations were found in 31%(9/29) of patients; 7 of these mutations were novel and another was the L858R mutation. All missense mutations were found to be activating mutations and responsive to erlotinib. Of the 25 patients managed surgically, there were 7 mut+ and 18 mut-. Two of 7 (29%) mut+ developed progressive disease and died with a median follow-up time of 22 months; while 13/18 (72%) mut- developed progressive disease and 10/18 (56%) died with median TTP of 12 months and median survival of 14 months.ConclusionsThe novel EGFR mutations identified are activating mutations responsive to erlotinib. The mut+ subset have a 'relative' improved outcome. Erlotinib may have a role in MPM and exploration for mutations in a larger patient cohort is warranted.

【 授权许可】

CC BY   
© Foster et al; licensee BioMed Central Ltd. 2010