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Prognostic and predictive role of EGFR pathway alterations in biliary cancer patients treated with chemotherapy and anti-EGFR.
- Source :
-
PloS one [PLoS One] 2018 Jan 19; Vol. 13 (1), pp. e0191593. Date of Electronic Publication: 2018 Jan 19 (Print Publication: 2018). - Publication Year :
- 2018
-
Abstract
- The association of anti-EGFR to gemcitabine and oxaliplatin (GEMOX) chemotherapy did not improve survival in biliary tract carcinoma (BTC) patients. Multiple mechanisms might be involved in the resistance to anti-EGFR. Here, we explored the mutation profile of EGFR extracellular domain (ECD), of tyrosine kinase domain (TKD), and its amplification status. EGFR mutational status of exons 12, 18-21 was analyzed in 57 tumors by Sanger sequencing. EGFR amplification was evaluated in 37 tumors by Fluorescent In Situ Hybridization (FISH). Kaplan-Meier curves were calculated using the log-rank test. Six patients had mutations in exon 12 of EGFR ECD and 7 in EGFR TKD. Neither EGFR ECD nor TKD mutations affected progression free survival (PFS) or overall survival (OS) in the entire population. In the panitumumab plus GEMOX (P-GEMOX) arm, ECD mutated patients had a worse OS, while EGFR TKD mutated patients had a trend towards shorter PFS and OS. Overall, the presence of mutations in EGFR or in its transducers did not affect PFS or OS, while the extrahepatic cholangiocarcinoma (ECC) mutated patients had a worse prognosis compared to WT. Nineteen out of 37 tumors were EGFR amplified, but the amplification did not correlate with survival. ECC EGFR amplified patients had improved OS, whereas the amplification significantly correlated with poor PFS (p = 0.03) in gallbladder carcinoma patients. The high molecular heterogeneity is a predominant feature of BTC: the alterations found in this work seem to have a prognostic impact rather than a predictive role towards anti-EGFR therapy.
- Subjects :
- Antibodies, Monoclonal administration & dosage
Antibodies, Monoclonal therapeutic use
Antineoplastic Combined Chemotherapy Protocols administration & dosage
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Bile Duct Neoplasms drug therapy
Bile Duct Neoplasms genetics
Bile Duct Neoplasms metabolism
Biliary Tract Neoplasms metabolism
Cholangiocarcinoma drug therapy
Cholangiocarcinoma genetics
Cholangiocarcinoma metabolism
DNA Mutational Analysis
Deoxycytidine administration & dosage
Deoxycytidine analogs & derivatives
Deoxycytidine therapeutic use
ErbB Receptors antagonists & inhibitors
ErbB Receptors metabolism
Gallbladder Neoplasms drug therapy
Gallbladder Neoplasms genetics
Gallbladder Neoplasms metabolism
Gene Amplification
Humans
In Situ Hybridization, Fluorescence
Kaplan-Meier Estimate
Organoplatinum Compounds administration & dosage
Organoplatinum Compounds therapeutic use
Oxaliplatin
Panitumumab
Prognosis
Gemcitabine
Biliary Tract Neoplasms drug therapy
Biliary Tract Neoplasms genetics
ErbB Receptors genetics
Genes, erbB-1
Mutation
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 13
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 29352306
- Full Text :
- https://doi.org/10.1371/journal.pone.0191593