MRNA EXPRESSION OF PLATELET-DERIVED GROWTH FACTOR RECEPTOR-β AND C-KIT: CORRELATION WITH PATHOLOGIC RESPONSE TO CETUXIMAB-BASED CHEMORADIOTHERAPY IN PATIENTS WITH RECTAL CANCER

Purpose: Deviant expression of platelet-derived growth factor receptor-beta (PDGFR beta) and e-kit was shown in patients with colorectal cancer. In the present study, mRNA expression of PDGFR beta and c-kit in 33 patients with locally advanced rectal cancer undergoing preoperative chemoradiotherapy with cetuximab/capecitabine/ irinotecan in correlation with the tumor regression rate was investigated. Methods and Materials: Pretherapeutic biopsy cores and tumor material from the resected specimens were collected in parallel with normal rectal mucosa. The expression levels of PDGFR beta and c-kit were measured by quantitative polymerase chain reaction. Tumors were classified as good responders (tumor regression grade [TRG], 2-3) or poor responders (TRG, 0-1). Results: The TRG evaluation of the resected specimen was TRG 0-1 in 11 and TRG 2-3 in 22. The median normalized ratios in the pretreatment mucosa vs. tumor biopsy cores was as follows: PDGFR beta ratio of 15.2 vs. 49.5 (p <0.0001) and c-kit ratio of 0.94 vs. 0.67 (p = 0.014). The same tendency was observed for the median PDGFR beta ratios after chemoradiotherapy completion: 34.2 vs. 170.0 (p <0.0001). The PDGFR beta and c-kit mRNA expression values in the pretreatment tumor biopsy cores were lower than the values in the resected specimens: PDGFR beta ratio 49.5 vs. 170.0 (p = 0.0002) and c-kit ratio 0.67 vs. 1.1 (p = 0.0003). Nevertheless, no correlation was seen between the pretherapeutic PDGFR beta and c-kit mRNA expression and the pathologic regression rate. Conclusion: Cetuximab-based chemoradiotherapy increased PDGFR beta levels even further compared with the pretreatment samples and deserves further investigation. (c) 2008 Elsevier Inc.