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

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).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).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.Activation of the epidermal growth factor receptor (EGFR) is related to cell proliferation, metastasis and angiogenesis in many tumors [1]. In colorectal carcinoma (CRC) patients, EGFR is over-expressed in 75% of the tumors and its over-expression is associated with worse outcome [2]. EGFR was therefore an obvious candidate for targeted therapy in this malignancy. Cetuximab is an IgG1 anti-EGFR monoclonal antibody (moAb) that binds to the ligand-binding domain of the EGFR, leading to inhibition of its proliferative activity. Its use in the clinic has resulted in response rates (RR) of 23–25% in combination with chemotherapy and 10% as a single agent [3]. The most common side effect of cetuximab is an acneiform rash, which, however, seems to be positively associated with response and overall survival [4].In order to avoid the unnec