In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 25, No. 18_suppl ( 2007-06-20), p. 15039-15039
Abstract:
15039 Background: Patients with chemoresponsive tumors are more likely to have a survival advantage, consequently a great interest is being placed on the identification of predictive markers. Currently, the improving in the extraction techniques allow the detection of gene profile at the mRNA level from FFPE materials. The purpose of the study was to analyse the m-RNA level of specific genes from FFPE (Stanta et al, BioTechniques 1998), both primary tumor (T) and locoregional lymphnodes (N) in CRC patients treated with chemotherapy (CT), and to relate it with chemoresponsiveness. Material and Methods: RNA was extract from FFPE tumor specimen both in T and N. RNA was reversing transcribed to cDNA. From the cDNA sample, BRCA1, ERCC1, CES2 and TS gene transcripts were specifically amplified by PCR. ERCC1 and BRCA1 are involved in platinum-compound resistance; TS is involved in responses to 5Fluorouracil (5FU) and CES2 level expression was recently related to Irinotecan pro-drug activation. Eligible patients included metastatic CRC patients treated from March 2000 to December 2003 as first line CT with Oxaliplatin/5FU or Irinotecan/5FU or 5FU alone. Results: Forty-five consecutive patients were retrospectively analysed. 15 of them received Oxaliplatin/5FU, 15 Irinotecan/5FU and the other 15 5FU alone. Median age was 64 (range 46–75). 13 patients (28%) had received adjuvant CT. 32 patients (72%) had metastatic disease at the time of surgery. Global Response Rate was 44%. All 45 patients received 5FU and they were analysed for the level of TS expression. With Multiple Regression Analysis, no statistical significant relation between TS level expression and response to 5FU was observed (P=0.36). A strong relation was observed between ERCC1 and response to Oxaliplatin (P=0.006) and a possible correlation of BRCA1-exon11 level expression and response to Irinotecan (P=0.06). The analyses of CES2 and the relation between gene expression and survival are ongoing. Conclusions: The analyses of mRNA gene expression profile from FFPE could be use to predicting response to CT in CRC patients. To test this hypothesis, a randomized phase II-III prospective study of tailored therapy in metastatic CRC is planned. No significant financial relationships to disclose.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2007.25.18_suppl.15039
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2007
detail.hit.zdb_id:
2005181-5
Bookmarklink