title: Telomerase expression as a predictive marker of radiotherapy response in rectal cancer.
abstract: OBJECTIVE
  To investigate telomerase as a predictive marker of radiotherapy response in rectal cancer.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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. j.shin@uws.edu.au
authors.forename: Joo-Shik
authors.initials: JS
authors.lastname: Shin
authors.forename: Terence
authors.initials: T
authors.lastname: Foo
authors.forename: Angela
authors.initials: A
authors.lastname: Hong
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
authors.forename: Trina
authors.initials: T
authors.lastname: Lum
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Solomon
authors.forename: C Soon
authors.initials: CS
authors.lastname: Lee
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D045744:Cell Line, Tumor; D003082:Colectomy; D003110:Colonic Neoplasms / Q000201:enzymology / Q000532:radiotherapy*; D006801:Humans; D009929:Organ Size; D011237:Predictive Value of Tests; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; C509186:TERT protein, human; D019098:Telomerase