A1 Refereed original research article in a scientific journal
Preoperative radiotherapy downregulates the nuclear expression of hypoxia-inducible factor-1 alpha in rectal cancer
Authors: Korkeila E, Jaakkola PM, Syrjanen K, Sundstrom J, Pyrhonen S
Publisher: TAYLOR & FRANCIS AS
Publication year: 2010
Journal: Scandinavian Journal of Gastroenterology
Journal name in source: SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY
Journal acronym: SCAND J GASTROENTERO
Number in series: 3
Volume: 45
Issue: 3
First page : 340
Last page: 348
Number of pages: 9
ISSN: 0036-5521
DOI: https://doi.org/10.3109/00365520903483635
Abstract
Objective. To assess the value of hypoxia-inducible factor-1 alpha (HIF-1 alpha) expression as a predictor of disease outcome in rectal cancer treated by preoperative radio- or chemoradiotherapy. Material and methods. Operative samples from 168 rectal cancer patients and 79 respective preoperative biopsies were analyzed for nuclear HIF-1 alpha protein expression using immunohistochemistry by three approaches: (a) positive/negative, (b) the percentage of HIF-positive cancer cells and (c) staining intensity. The patients had received either short- (n = 75) or long-course radiotherapy with or without chemotherapy (n = 39) or no treatment preoperatively (n = 54). Results. HIF-1 alpha staining was positive in 70% of the diagnostic biopsies but negative in most of the post-radiotherapy specimens (60%). HIF-1 alpha expression in the biopsies was downregulated in 56% of samples taken after preoperative treatment, while negative HIF-1 alpha expression was upregulated in 25% of samples. Patients who had HIF-negative tumours after long-course radiotherapy had significantly (P = 0.001) better disease-specific survival (DSS) in univariate analysis. In the multivariate (Cox) regression model, HIF-1 alpha lost its significance and only being in the preoperative treatment group was an independent predictor of disease-free survival. In a similar Cox model, disease recurrence and the number of metastatic lymph nodes were independent predictors of DSS. Conclusions. HIF-1 alpha expression was positive in most of the preoperative biopsies but downregulated in most of the operative samples, implicating that preoperative radiotherapy downregulates HIF-1 alpha expression in rectal cancer. Negative HIF expression after preoperative long-course radiotherapy was associated with significantly better DSS.
Objective. To assess the value of hypoxia-inducible factor-1 alpha (HIF-1 alpha) expression as a predictor of disease outcome in rectal cancer treated by preoperative radio- or chemoradiotherapy. Material and methods. Operative samples from 168 rectal cancer patients and 79 respective preoperative biopsies were analyzed for nuclear HIF-1 alpha protein expression using immunohistochemistry by three approaches: (a) positive/negative, (b) the percentage of HIF-positive cancer cells and (c) staining intensity. The patients had received either short- (n = 75) or long-course radiotherapy with or without chemotherapy (n = 39) or no treatment preoperatively (n = 54). Results. HIF-1 alpha staining was positive in 70% of the diagnostic biopsies but negative in most of the post-radiotherapy specimens (60%). HIF-1 alpha expression in the biopsies was downregulated in 56% of samples taken after preoperative treatment, while negative HIF-1 alpha expression was upregulated in 25% of samples. Patients who had HIF-negative tumours after long-course radiotherapy had significantly (P = 0.001) better disease-specific survival (DSS) in univariate analysis. In the multivariate (Cox) regression model, HIF-1 alpha lost its significance and only being in the preoperative treatment group was an independent predictor of disease-free survival. In a similar Cox model, disease recurrence and the number of metastatic lymph nodes were independent predictors of DSS. Conclusions. HIF-1 alpha expression was positive in most of the preoperative biopsies but downregulated in most of the operative samples, implicating that preoperative radiotherapy downregulates HIF-1 alpha expression in rectal cancer. Negative HIF expression after preoperative long-course radiotherapy was associated with significantly better DSS.
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