Korkeila E, Jaakkola P M, Syrjänen K, Sundström J, Pyrhönen S
Department of Oncology and Radiotherapy, University of Turku and Turku University Hospital, Turku, Finland.
Scand J Gastroenterol. 2010 Mar;45(3):340-8. doi: 10.3109/00365520903483635.
To assess the value of hypoxia-inducible factor-1alpha (HIF-1alpha) expression as a predictor of disease outcome in rectal cancer treated by preoperative radio- or chemoradiotherapy.
Operative samples from 168 rectal cancer patients and 79 respective preoperative biopsies were analyzed for nuclear HIF-1alpha 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).
HIF-1alpha staining was positive in 70% of the diagnostic biopsies but negative in most of the post-radiotherapy specimens (60%). HIF-1alpha expression in the biopsies was downregulated in 56% of samples taken after preoperative treatment, while negative HIF-1alpha 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-1alpha 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.
HIF-1alpha expression was positive in most of the preoperative biopsies but downregulated in most of the operative samples, implicating that preoperative radiotherapy downregulates HIF-1alpha expression in rectal cancer. Negative HIF expression after preoperative long-course radiotherapy was associated with significantly better DSS.
评估缺氧诱导因子-1α（HIF-1α）表达作为术前放疗或放化疗治疗直肠癌疾病预后预测指标的价值。
采用免疫组织化学方法，通过三种途径分析168例直肠癌患者的手术标本及79例相应的术前活检标本中核HIF-1α蛋白的表达情况：（a）阳性/阴性；（b）HIF阳性癌细胞的百分比；（c）染色强度。患者术前接受了短程放疗（n = 75）或长程放疗联合或不联合化疗（n = 39），或未接受任何治疗（n = 54）。
70%的诊断性活检标本中HIF-1α染色呈阳性，但大多数放疗后标本（60%）呈阴性。术前治疗后，56%的活检标本中HIF-1α表达下调，而25%的标本中HIF-1α阴性表达上调。在单因素分析中，长程放疗后HIF阴性肿瘤患者的疾病特异性生存率（DSS）显著更高（P = 0.001）。在多因素（Cox）回归模型中，HIF-1α失去其显著性，仅术前治疗组是无病生存的独立预测因素。在类似的Cox模型中，疾病复发和转移淋巴结数量是DSS的独立预测因素。
大多数术前活检标本中HIF-1α表达呈阳性，但大多数手术标本中表达下调，这表明术前放疗可下调直肠癌中HIF-1α的表达。术前长程放疗后HIF阴性表达与显著更好的DSS相关。
