Novel and existing mutations in the EGF receptor tyrosine kinase domain are predictors of optimal resectability (OR) in malignant peritoneal mesothelioma (MPM)
| Autor: | Jason M. Foster, Brian W. Loggie, S. Lilleberg, G. Haynatzki, Zoran Gatalica |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Cancer Research Pathology medicine.medical_specialty biology business.industry medicine.disease Receptor tyrosine kinase Domain (software engineering) Oncology Malignant Peritoneal Mesothelioma biology.protein medicine Cancer research Mesothelioma business Median survival |
| Zdroj: | Journal of Clinical Oncology. 25:10503-10503 |
| ISSN: | 1527-7755 0732-183X |
| Popis: | 10503 Background: MPMs represent 20% of all malignant mesothelioma (MM) cases. The median survival for these tumors is less than a year, and like other peritoneal tumors this is due to intra-abdominal recurrence/progression. Currently there is a paucity of information about the biology of these tumors and molecular perturbations that are involved in tumor formation. Elucidation of mutations and biological pathways active in these tumors may identify valuable prognostic markers, as well as facilitate the development of novel therapies. Methods: Twenty-nine MPM patients were evaluated at a single tertiary center and their tumors were probed for mutations in the catalytic TK domain of EGF receptor (mut+). All specimens were examined for somatic mutations by PCR amplification. Twenty-five patients were treated with cytoreductive surgery (CRS) ± IPHC and complete clinical data including age, sex, cytoreductive score, histology, mutation, and survival was available for comparison of the mut+ and mut- groups. Results: The median age was 56, and 71% of the patients were male with a median follow-up time (MFT) of 14.5 months. Mutations were found in 31% (9/29) of the tumors, 7 of these mutations were novel, and the 8th one was the L858R mutation described in NSCLC. Of the 25 patients managed surgically there were 7 mut+ and 18 mut- ( Table ). OR (=R2a) was achieved in 7/7 (100%) of mut+ group and 9/18 (50%) mut- (p=.03). All mut+ are alive with a MFT of 24 months, while 5/18 (28%) of the mut- group are DOD with a MFT of 7 months (p=.27). In an ANCOVA model OR (p=0.04) was found to be predictive of survival. Conclusions: The EGFR-TK appears to be a common site for mutation in MPM, with the identification of novel and known activation mutation in 31% of tumors. Mut+ was predictive of OR. OR was predictive of survival in short term follow-up, and with longer follow-up, mut+ may be predictive of survival as well as represent a subset of patients who may be responsive to TK-inhibitors therapy. [Table: see text] No significant financial relationships to disclose. |
| Databáze: | OpenAIRE |
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