The status of EGFR-associated genes could predict the outcome and tumor response of chemo-refractory metastatic colorectal patients using cetuximab and chemotherapy

Jen-Kou Lin; An-Jen Lin; Chun-Chi Lin; Yuan-Tzu Lan; Shung-Haur Yang; Anna Fen-Yau Li; Shih-Ching Chang

doi:10.1002/jso.21993

The status of EGFR-associated genes could predict the outcome and tumor response of chemo-refractory metastatic colorectal patients using cetuximab and chemotherapy

J Surg Oncol. 2011 Nov 1;104(6):661-6. doi: 10.1002/jso.21993. Epub 2011 Jun 13.

Authors

Jen-Kou Lin¹, An-Jen Lin, Chun-Chi Lin, Yuan-Tzu Lan, Shung-Haur Yang, Anna Fen-Yau Li, Shih-Ching Chang

Affiliation

¹ Division of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan.

PMID: 21671463
DOI: 10.1002/jso.21993

Abstract

Purpose: This study was designed to analyze the impacts of status of EGFR-associated genes on the outcome of chemo-refractory mCRC patients using cetuximab.

Materials and methods: We collected samples from 42 metastatic CRC patients refractory to FOLFOX or FOLFIRI. Mutation profiles of KRAS, BRAF, PTEN, and PI3KCA and the copy numbers of EGFR and PTEN were analyzed. Overall survival and tumor response between various statuses of EGFR-associated genes were compared.

Results: Eleven patients had a partial response to cetuximab with chemotherapy. Sixteen (38.1%) tumors had KRAS mutations. Three (7.1%) had BRAF mutations (V600E) and three (7.1%) had PTEN mutations. No PIK3CA mutation was found. Of 26 wild-KRAS tumors, nine (34.6%) had a partial response to cetuximab: this was higher than that of KRAS-mutated tumors (12.5%). Five patients with BRAF or PTEN mutations did not response to cetuximab. Response rate increased to 45% in patients with all wild-type KRAS, BRAF, and PTEN tumors. Of 16 tumors with high EGFR copy number, eight (50%) responded to cetuximab, a higher response rate than that of tumors with normal EGFR copy number (3/26, P = 0.011). Overall survival of patients was associated with high EGFR copy number and all wild-type tumors.

Conclusion: EFGR copy number and mutation in EGFR-associated genes could be selective markers in mCRC patients using cetuximab.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal / therapeutic use*
Antibodies, Monoclonal, Humanized
Antineoplastic Agents / therapeutic use
Antineoplastic Combined Chemotherapy Protocols / adverse effects*
Camptothecin / administration & dosage
Camptothecin / analogs & derivatives
Cetuximab
Class I Phosphatidylinositol 3-Kinases
Colorectal Neoplasms / drug therapy
Colorectal Neoplasms / genetics*
Colorectal Neoplasms / pathology
Drug Resistance, Neoplasm / genetics*
ErbB Receptors / genetics*
Female
Follow-Up Studies
Gene Expression Regulation, Neoplastic
Humans
Irinotecan
Liver Neoplasms / drug therapy
Liver Neoplasms / genetics*
Liver Neoplasms / secondary
Lymphatic Metastasis
Male
Middle Aged
Mutation / genetics*
Neoplasm Recurrence, Local / diagnosis
Neoplasm Recurrence, Local / drug therapy
Neoplasm Recurrence, Local / genetics
Organoplatinum Compounds / administration & dosage
Oxaliplatin
PTEN Phosphohydrolase / genetics
Phosphatidylinositol 3-Kinases / genetics
Proto-Oncogene Proteins B-raf / genetics
Retrospective Studies
Salvage Therapy*
Survival Rate
Treatment Outcome

Substances

Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
Antineoplastic Agents
Organoplatinum Compounds
Oxaliplatin
Irinotecan
Phosphatidylinositol 3-Kinases
Class I Phosphatidylinositol 3-Kinases
PIK3CA protein, human
EGFR protein, human
ErbB Receptors
BRAF protein, human
Proto-Oncogene Proteins B-raf
PTEN Phosphohydrolase
PTEN protein, human
Cetuximab
Camptothecin