Department of Anatomical Pathology, Liverpool Hospital, and Discipline of Pathology and Cancer Biology Laboratory, School of Medicine, University of Western Sydney, New South Wales, Australia.
Pathology. 2012 Apr;44(3):209-15. doi: 10.1097/PAT.0b013e3283511cd5.
To investigate telomerase as a predictive marker of radiotherapy response in rectal cancer.
Expression of the telomerase catalytic subunit hTERT was quantified with reverse transcription PCR in the radioresistant colorectal cancer cell line SW620 following exposure to 5Gy of radiation. Additionally, 52 rectal cancer cases were pre-operatively treated with either the short (n = 19) or long (n = 33) course radiotherapy (SCR, LCR, respectively) regimes, before and after which their hTERT expressions were semi-quantified with immunohistochemistry (IHC). This was correlated with the histological tumour regression in the resected bowel, dichotomised into good and poor responses.
SW620 cells expressed gradually increasing levels of hTERT after radiation. hTERT IHC positivity of ≤75% tumour cells in pre-radiotherapied cancer was the optimal negative cut-off level [sensitivity 63.2%, specificity 45.8%, area under curve (AUC) 0.5362] in predicting good tumour response. As significantly more LCR cases showed good tumour response (p<0.0001), the SCR cases were excluded and AUC re-analysed, which still remained low (0.5357).
While our in vitro results suggest that hTERT up-regulation may contribute to radiation resistance of colorectal cancer cells, our in vivo results demonstrated poor ability of hTERT IHC in predicting histological tumour regression in rectal cancer.
探讨端粒酶作为直肠癌放疗反应预测标志物的作用。
采用逆转录 PCR 法检测耐辐射结直肠癌细胞系 SW620 中端粒酶催化亚单位 hTERT 在接受 5Gy 照射后的表达情况。另外，52 例直肠癌患者分别接受短程（n=19）或长程（n=33）放疗（分别为 SCR 和 LCR）治疗，在治疗前后采用免疫组化法（IHC）对其 hTERT 表达进行半定量检测。并将 hTERT 表达与切除肠段的组织学肿瘤消退程度相关联，分为良好和不良反应。
SW620 细胞在接受辐射后 hTERT 表达逐渐增加。放疗前 hTERT IHC 阳性肿瘤细胞比例≤75%是预测良好肿瘤反应的最佳阴性截断值（敏感性 63.2%，特异性 45.8%，曲线下面积（AUC）0.5362）。由于 LCR 组中更多的病例显示出良好的肿瘤反应（p<0.0001），排除 SCR 组后重新分析 AUC，其值仍较低（0.5357）。
虽然我们的体外结果表明 hTERT 的上调可能有助于结直肠癌细胞的辐射抵抗，但我们的体内结果表明 hTERT IHC 预测直肠癌组织学肿瘤消退的能力较差。
