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RESEARCH PRODUCT

Small Bowel Carcinomas in Coeliac or Crohn’s Disease: Clinico-pathological, Molecular, and Prognostic Features. A Study From the Small Bowel Cancer Italian Consortium

Claudia MescoliMichele MartinoFausto SessaMassimo RuggeOmbretta LuinettiGabriella NesiVincenzo CanzonieriAlessandro VanoliLuca Reggiani BonettiAda Maria FlorenaGiovanni MonteleoneDaniela FurlanUmberto VoltaPaolo FocianiVincenzo VillanacciAntonino Giulio GiannoneMarco SilanoAntonio Di SabatinoAntonio MaccioniPaolo UsaiG. SolinaVittorio PerfettiFederica GrilloMaria Cristina MacciomeiRachele MancaStefano FerreroRenato CannizzaroAroldo RizzoLivia BianconeLuca ElliClaudio PapiGiacomo CaioGiovanni LatellaAntonio CalabròRoberta CeruttiMarianna SalemmePaolo GiuffridaGianluca M. SampietroGino Roberto CorazzaPaola MiglioraDonatella SantiniSandro ArdizzoneAugusto OrlandiFrancesco TonelliAntonio CiardiCatherine KlersyCarolina CiacciDavide TrapaniRenata D'incàFrancesco Paolo D'armientoMarco PaulliMarco AstegianoRoberto CaronnaRoberto FioccaLuigi Michele CoppolaPaola AlberizziEnrico SolciaGiuseppe SanteusanioG. SandriRoberta Riboni

subject

Male0301 basic medicineNeuroblastoma RAS viral oncogene homologOncologySurvivalReceptor ErbB-2Colorectal cancermedicine.disease_causeInflammatory bowel diseaseInflammatory bowel diseasetumour-infiltrating lymphocyteErbB-20302 clinical medicineCrohn DiseaseRetrospective StudieRisk Factors80 and overChildClass I Phosphatidylinositol 3-KinaseAged 80 and overColonic NeoplasmSettore MED/12 - GastroenterologiaCrohn's diseaseMLH1 methylationTumour-infiltrating lymphocytesGastroenterologyGeneral MedicineMiddle AgedPrognosisInflammatory bowel disease; Microsatellite instability; MLH1 promoter methylation; Survival; Tumour-infiltrating lymphocytes; Gastroenterology030220 oncology & carcinogenesisColonic NeoplasmsSurvival AnalysiKRASHumanReceptorAdultProto-Oncogene Proteins B-rafmedicine.medical_specialtyPrognosiClass I Phosphatidylinositol 3-KinasesSettore MED/08 - Anatomia PatologicaNOProto-Oncogene Proteins p21(ras)MLH1 promoter methylationYoung Adult03 medical and health sciencesInternal medicinemedicineCarcinomaHumansMLH1 methylation; inflammatory bowel disease; microsatellite instability; survival; tumour-infiltrating lymphocytesneoplasmsAgedRetrospective StudiesInflammatory bowel disease; Microsatellite instability; MLH1 promoter methylation; Survival; Tumour-infiltrating lymphocytes; Adult; Aged; Aged 80 and over; Celiac Disease; Child; Class I Phosphatidylinositol 3-Kinases; Colonic Neoplasms; Crohn Disease; Humans; Male; Microsatellite Instability; Middle Aged; Prognosis; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras); Receptor ErbB-2; Retrospective Studies; Risk Factors; Survival Analysis; Tumor Suppressor Protein p53; Young Adult; Gastroenterologybusiness.industryTumour-infiltrating lymphocyteRisk FactorCancerMicrosatellite instabilityinflammatory bowel disease; microsatellite instability; MLH1 promoter methylation; tumour-infiltrating lymphocytes; survivalmedicine.diseaseSurvival Analysiseye diseasesdigestive system diseasesCeliac Disease030104 developmental biologyMicrosatellite instabilityTumor Suppressor Protein p53business

description

Background and aims An increased risk of small bowel carcinoma [SBC] has been reported in coeliac disease [CD] and Crohn's disease [CrD]. We explored clinico-pathological, molecular, and prognostic features of CD-associated SBC [CD-SBC] and CrD-associated SBC [CrD-SBC] in comparison with sporadic SBC [spo-SBC]. Methods A total of 76 patients undergoing surgical resection for non-familial SBC [26 CD-SBC, 25 CrD-SBC, 25 spo-SBC] were retrospectively enrolled to investigate patients' survival and histological and molecular features including microsatellite instability [MSI] and KRAS/NRAS, BRAF, PIK3CA, TP53, HER2 gene alterations. Results CD-SBC showed a significantly better sex-, age-, and stage-adjusted overall and cancer-specific survival than CrD-SBC, whereas no significant difference was found between spo-SBC and either CD-SBC or CrD-SBC. CD-SBC exhibited a significantly higher rate of MSI and median tumour-infiltrating lymphocytes [TIL] than CrD-SBC and spo-SBC. Among the whole SBC series, both MSI─which was the result of MLH1 promoter methylation in all but one cases─and high TIL density were associated with improved survival at univariable and stage-inclusive multivariable analysis. However, only TILs retained prognostic power when clinical subgroups were added to the multivariable model. KRAS mutation and HER2 amplification were detected in 30% and 7% of cases, respectively, without prognostic implications. Conclusions In comparison with CrD-SBC, CD-SBC patients harbour MSI and high TILs more frequently and show better outcome. This seems mainly due to their higher TIL density, which at multivariable analysis showed an independent prognostic value. MSI/TIL status, KRAS mutations and HER2 amplification might help in stratifying patients for targeted anti-cancer therapy.

yearjournalcountryeditionlanguage
2017-01-01Journal of Crohn's and Colitis
https://doi.org/10.1093/ecco-jcc/jjx031