title: Loss of PTEN expression as a predictor of resistance to anti-EGFR monoclonal therapy in metastatic colorectal cancer: evidence from retrospective studies.
abstract: OBJECTIVE
  To investigate the predictive value of loss of PTEN expression in patients with metastatic colorectal cancer (mCRC) treated with anti-EGFR monoclonal therapy.
  
  
  METHODS
  Studies were systematically identified to investigate the relationship between PTEN expression and clinical outcome in mCRC patients treated with anti-EGFR MoAbs. Clinical outcomes included objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). The pooled relative risk (RR) or hazard ratio (HR) was estimated using a fixed-effects model or a random-effects model according to the heterogeneity between the studies.
  
  
  RESULTS
  A total of 852 patients were included in the final meta-analysis. The rate of loss of PTEN expression was 28.4% (242/852). The overall pooled RR for ORR was 0.413 (95% confidence intervals (CI), 0.177-0.965) when patients with loss of PTEN expression were compared with those with normal PTEN expression. Anti-EGFR monoclonal therapy resulted in improved PFS (HR, 0.466; 95% CI, 0.292-0.640) and OS (HR, 0.689 [95% CI, 0.482-0.896]) in patients unselected by KRAS mutation with normal PTEN expression over loss of PTEN expression. A better prognosis, as reflected by PFS (HR, 0.344; 95% CI, 0.154-0.533) and OS (HR, 0.544; 95% CI, 0.285-0.803), was observed in wild-type KRAS patients with normal PTEN expression versus loss of expression.
  
  
  CONCLUSIONS
  Loss of expression of PTEN is a potential biomarker for resistance to anti-EGFR monoclonal therapy, particularly in mCRC patients with KRAS wild type.
authors.affiliation: Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Shanghai Jiao-Tong University School of Medicine Renji Hospital, 145 Middle Shandong Rd, Shanghai, 200001, China. zhenhuaw@sjtu.edu.cn
authors.forename: Zhen-Hua
authors.initials: ZH
authors.lastname: Wang
authors.forename: Qin-Yan
authors.initials: QY
authors.lastname: Gao
authors.forename: Jing-Yuan
authors.initials: JY
authors.lastname: Fang
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000276:immunology*; D006801:Humans; D009154:Mutation; D009362:Neoplasm Metastasis; D051059:PTEN Phosphohydrolase / Q000032:analysis*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D018631:ras Proteins / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D066246:ErbB Receptors; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins