PMID- 20117921 OWN - NLM STAT- MEDLINE DCOM- 20100805 LR - 20181201 IS - 1433-2981 (Electronic) IS - 0936-6555 (Linking) VI - 22 IP - 4 DP - 2010 May TI - Gene expression profiles of epidermal growth factor receptor, vascular endothelial growth factor and hypoxia-inducible factor-1 with special reference to local responsiveness to neoadjuvant chemoradiotherapy and disease recurrence after rectal cancer surgery. PG - 272-80 LID - 10.1016/j.clon.2010.01.001 [doi] AB - AIMS: To establish a causal relationship between the gene expression profiles of angiogenetic molecular markers, including epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1 (HIF-1), in rectal cancer and the local responsiveness to neoadjuvant chemoradiotherapy and subsequent disease recurrence. MATERIALS AND METHODS: We examined the pre-treatment tumour biopsies (n=40) obtained from patients with rectal adenocarcinoma (clinical International Union Against Cancer stage ll/III) who were scheduled to receive neoadjuvant 5-fluorouracil-based chemoradiotherapy for EGFR, VEGF and HIF-1 expression by quantitative real-time polymerase chain reaction. RESULTS: Responders (patients with significant tumour regression, i.e. pathological grades 2/3) showed significantly lower VEGF, HIF-1 and EGFR gene expression levels than the non-responders (patients with insignificant tumour regression, i.e. pathological grades 0/1) in the pre-treatment tumour biopsies. The elevated expression level of each gene could predict patients with a low response to chemoradiation. During the median follow-up of all patients (41 months; 95% confidence interval 28-60 months), 6/40 (15%) developed disease recurrence. Although local responsiveness to neoadjuvant chemoradiotherapy was associated with neither local nor systemic disease recurrence, lymph node metastasis and an elevated VEGF gene expression level were independent predictors of systemic disease recurrence. The 3-year disease-free survival rates of the patients with lower VEGF or EGFR expression levels were significantly lower than those of patients with higher VEGF or EGFR expression levels. CONCLUSIONS: Analysing VEGF expression levels in rectal cancer may be of benefit in estimating the effects of neoadjuvant chemoradiotherapy and in predicting systemic recurrence after rectal cancer surgery. CI - Copyright 2010 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. FAU - Toiyama, Y AU - Toiyama Y AD - Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Edobashi 2-174 Tsu, Mie 514-8507, Japan. ytoi0725@clin.medic.mie-u.ac.jp FAU - Inoue, Y AU - Inoue Y FAU - Saigusa, S AU - Saigusa S FAU - Okugawa, Y AU - Okugawa Y FAU - Yokoe, T AU - Yokoe T FAU - Tanaka, K AU - Tanaka K FAU - Miki, C AU - Miki C FAU - Kusunoki, M AU - Kusunoki M LA - eng PT - Journal Article DEP - 20100201 PL - England TA - Clin Oncol (R Coll Radiol) JT - Clinical oncology (Royal College of Radiologists (Great Britain)) JID - 9002902 RN - 0 (Antimetabolites, Antineoplastic) RN - 0 (Biomarkers, Tumor) RN - 0 (HIF1A protein, human) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (RNA, Messenger) RN - 0 (VEGFA protein, human) RN - 0 (Vascular Endothelial Growth Factor A) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ErbB Receptors) RN - U3P01618RT (Fluorouracil) SB - IM MH - Adenocarcinoma/genetics/metabolism/therapy MH - Aged MH - Antimetabolites, Antineoplastic/therapeutic use MH - Biomarkers, Tumor/genetics/metabolism MH - Combined Modality Therapy MH - ErbB Receptors/*genetics/metabolism MH - Female MH - Fluorouracil/*therapeutic use MH - Gene Expression Profiling MH - Humans MH - Hypoxia-Inducible Factor 1, alpha Subunit/*genetics/metabolism MH - Lymphatic Metastasis MH - Male MH - Middle Aged MH - *Neoadjuvant Therapy MH - Neoplasm Recurrence, Local/*genetics/metabolism/therapy MH - Oligonucleotide Array Sequence Analysis MH - RNA, Messenger/genetics/metabolism MH - Radiotherapy Dosage MH - Rectal Neoplasms/*genetics/metabolism/therapy MH - Reverse Transcriptase Polymerase Chain Reaction MH - Survival Rate MH - Treatment Outcome MH - Vascular Endothelial Growth Factor A/*genetics/metabolism EDAT- 2010/02/02 06:00 MHDA- 2010/08/06 06:00 CRDT- 2010/02/02 06:00 PHST- 2009/03/25 00:00 [received] PHST- 2009/12/14 00:00 [revised] PHST- 2009/12/15 00:00 [accepted] PHST- 2010/02/02 06:00 [entrez] PHST- 2010/02/02 06:00 [pubmed] PHST- 2010/08/06 06:00 [medline] AID - S0936-6555(10)00002-6 [pii] AID - 10.1016/j.clon.2010.01.001 [doi] PST - ppublish SO - Clin Oncol (R Coll Radiol). 2010 May;22(4):272-80. doi: 10.1016/j.clon.2010.01.001. Epub 2010 Feb 1.