title: Potential value of PTEN in predicting cetuximab response in colorectal cancer: an exploratory study.
abstract: BACKGROUND
  The epidermal growth factor receptor (EGFR) is over-expressed in 70-75% of colorectal adenocarcinomas (CRC). The anti-EGFR monoclonal antibody cetuximab has been approved for the treatment of metastatic CRC, however tumor response to cetuximab has not been found to be associated with EGFR over-expression by immunohistochemistry (IHC). The aim of this study was to explore EGFR and the downstream effector phosphatase and tensin homologue deleted on chromosome 10 (PTEN) as potential predictors of response to cetuximab.
  
  
  METHODS
  CRC patients treated with cetuximab by the Hellenic Cooperative Oncology group, whose formalin-fixed paraffin-embedded tumor tissue was available, were included. Tissue was tested for EGFR and PTEN by IHC and fluorescence in situ hybridization (FISH).
  
  
  RESULTS
  Eighty-eight patients were identified and 72 were included based on the availability of tissue blocks with adequate material for analysis on them. All patients, except one, received cetuximab in combination with chemotherapy. Median follow-up was 53 months from diagnosis and 17 months from cetuximab initiation. At the time of the analysis 53% of the patients had died. Best response was complete response in one and partial response in 23 patients. In 16 patients disease stabilized. Lack of PTEN gene amplification was associated with more responses to cetuximab and longer time to progression (p = 0.042).
  
  
  CONCLUSIONS
  PTEN could be one of the molecular determinants of cetuximab response. Due to the heterogeneity of the population and the retrospective nature of the study, our results are hypothesis generating and should be approached with caution. Further prospective studies are needed to validate this finding.
authors.affiliation: 1st Department of Medical Oncology, Hygeia Hospital, Athens, Greece. e.razis@hygeia.gr
authors.forename: Evangelia
authors.initials: E
authors.lastname: Razis
authors.forename: Evangelos
authors.initials: E
authors.lastname: Briasoulis
authors.forename: Eleni
authors.initials: E
authors.lastname: Vrettou
authors.forename: Dimosthenis V
authors.initials: DV
authors.lastname: Skarlos
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Papamichael
authors.forename: Ioannis
authors.initials: I
authors.lastname: Kostopoulos
authors.forename: Epaminontas
authors.initials: E
authors.lastname: Samantas
authors.forename: Ioannis
authors.initials: I
authors.lastname: Xanthakis
authors.forename: Mattheos
authors.initials: M
authors.lastname: Bobos
authors.forename: Eleni
authors.initials: E
authors.lastname: Galanidi
authors.forename: Maria
authors.initials: M
authors.lastname: Bai
authors.forename: Ioanna
authors.initials: I
authors.lastname: Gikonti
authors.forename: Alona
authors.initials: A
authors.lastname: Koukouma
authors.forename: Georgia
authors.initials: G
authors.lastname: Kafiri
authors.forename: Pavlos
authors.initials: P
authors.lastname: Papakostas
authors.forename: Konstantine T
authors.initials: KT
authors.lastname: Kalogeras
authors.forename: Paris
authors.initials: P
authors.lastname: Kosmidis
authors.forename: George
authors.initials: G
authors.lastname: Fountzilas
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D011237:Predictive Value of Tests; D015996:Survival Rate
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D000068818:Cetuximab