Research article

Potential value of PTEN in predicting cetuximab response in colorectal cancer: An exploratory study

Evangelia Razis¹ , Evangelos Briasoulis² , Eleni Vrettou³ , Dimosthenis V Skarlos⁴ , Dimitrios Papamichael⁵ , Ioannis Kostopoulos³ , Epaminontas Samantas⁶ , Ioannis Xanthakis⁷ , Mattheos Bobos³ , Eleni Galanidi¹ , Maria Bai⁸ , Ioanna Gikonti⁹ , Alona Koukouma⁵ , Georgia Kafiri¹⁰ , Pavlos Papakostas¹¹ , Konstantine T Kalogeras^7,12 , Paris Kosmidis¹³ and George Fountzilas⁷

¹  1st Department of Medical Oncology, Hygeia Hospital, Athens, Greece

²  Department of Medical Oncology, Ioannina University Hospital, Ioannina, Greece

³  Department of Pathology, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece

⁴  2nd Department of Medical Oncology, Henry Dunant Hospital, Athens, Greece

⁵  Department of Medical Oncology, Bank of Cyprus Oncology Centre, Nicosia, Cyprus

⁶  3rd Department of Medical Oncology, Agii Anargiri Cancer Hospital, Athens, Greece

⁷  Department of Medical Oncology, Papageorgiou Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece

⁸  Department of Pathology, Ioannina University Hospital, Ioannina, Greece

⁹  Department of Pathology, Agia Olga Hospital, Athens, Greece

¹⁰  Department of Pathology, Hippokratio Hospital, Athens, Greece

¹¹  Department of Medical Oncology, Hippokratio Hospital, Athens, Greece

¹²  Data Office, Hellenic Cooperative Oncology Group, Athens, Greece

¹³  2nd Department of Medical Oncology, Hygeia Hospital, Athens, Greece

author email corresponding author email

BMC Cancer 2008, 8:234doi:10.1186/1471-2407-8-234

Published:	13 August 2008

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).

Conclusion

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.