Telomerase expression as a predictive marker of radiotherapy response in rectal cancer: in vitro and in vivo study

SummaryAimsTo investigate telomerase as a predictive marker of radiotherapy response in rectal cancer.MethodsExpression 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 immuno- histochemistry (IHC). This was correlated with the histological tumour regression in the resected bowel, dichotomised into good and poor responses.ResultsSW620 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).ConclusionsWhile 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.