title: KRAS Mutant Status, p16 and β-catenin Expression May Predict Local Recurrence in Patients Who Underwent Transanal Endoscopic Microsurgery (TEMS) for Stage I Rectal Cancer.
abstract: Transanal endoscopic microsurgery (TEMS) is emerging as an alternative treatment for rectal cancer Stage I. There remains a risk of local recurrence. The Aim of the study was to study the effect of biomarkers in local recurrence for Stage I rectal cancer following TEMS plus or minus radiotherapy.
  
  
  
  This is a case control study where we compared 10 early rectal cancers that had recurred, against 19 cases with no recurrence, total 29 patients (age=28.25-86.87, mean age=67.92 years, SD=14.91, Male, N=18, Female, N=11). All patients underwent TEMS for radiological Stage I rectal cancer (yT1N0M0 or yT2N0M0) established with combination of magnetic resonance imaging (MRI) and endorectal ultrasound. We prospectively collected all data on tumour histology, morphological features, as well as follow-up parameters. Molecular analysis was performed to identify their status on BRAF, KRAS, p16 O6-methylguanine-DNA methyltransferase (MGMT) and β-catenin.
  
  
  
  Out of 29 specimens analyzed, 19 were KRAS wild type (65.9%) and 10 mutant (34.5%). Recurrence of the tumour was noted in 10 cases (34.5%) from which 60% were pT1 (N=6) and 40% pT2 (N=4). There was a statistically significant association between KRAS mutant status and local recurrence (N=6, p=0.037). P16 expression greater than 5% (mean=10.8%, min=0, max=95) is linked with earlier recurrence within 11.70 months (N=7, p=0.004). Membranous β-catenin expression (N=12, 48%) was also related with KRAS mutant status (p=0.006) but not with survival (p>0.05). BRAF gene was found to be wild type in all cases tested (N=23).
  
  
  
  KRAS/p16/β-catenin could be used as a combined biomarker for prediction of local recurrence and stratification of the risk for further surgery.
authors: Department of Colorectal Surgery, King's College Hospital NHS Foundation Trust, Denmark Hill, London, U.K.
authors: Michail
authors: M
authors: Sideris
authors: Department of Colorectal Surgery, King's College Hospital NHS Foundation Trust, Denmark Hill, London, U.K.
authors: Jane
authors: J
authors: Moorhead
authors: Department of Colorectal Surgery, King's College Hospital NHS Foundation Trust, Denmark Hill, London, U.K.
authors: Salvador
authors: S
authors: Diaz-Cano
authors: Department of Colorectal Surgery, King's College Hospital NHS Foundation Trust, Denmark Hill, London, U.K.
authors: Ingvar
authors: I
authors: Bjarnason
authors: Department of Colorectal Surgery, King's College Hospital NHS Foundation Trust, Denmark Hill, London, U.K.
authors: Amyn
authors: A
authors: Haji
authors: Department of Colorectal Surgery, King's College Hospital NHS Foundation Trust, Denmark Hill, London, U.K. spapagrigoriadis@nhs.net.
authors: Savvas
authors: S
authors: Papagrigoriadis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism; D009367:Neoplasm Staging; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D012004:Rectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D000067369:Transanal Endoscopic Microsurgery; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; C117307:KRAS protein, human; D009363:Neoplasm Proteins; D051176:beta Catenin; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Colorectal cancer; KRAS; biomarkers; recurrence; transanal endoscopic microsurgery