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

Abstract

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.

Small Bowel Carcinomas Associated with Immune-Mediated Intestinal Disorders: the Current Knowledge

“…The underlying intestinal disorder, i.e. CD or CrD, has been demonstrated to be a stage-independent prognostic factor in patients undergoing surgery for SBC [2]. Although both CD and CrD are sustained by similar pathogenic mechanisms, namely T helper 1 and 17 immune responses [3], CD-associated SBC (CD-SBC) and CrD-associated SBC (CrD-SBC) represent distinct entities in terms of clinical, histopathological and molecular features ( Table 1).…”

“…Although both CD and CrD are sustained by similar pathogenic mechanisms, namely T helper 1 and 17 immune responses [3], CD-associated SBC (CD-SBC) and CrD-associated SBC (CrD-SBC) represent distinct entities in terms of clinical, histopathological and molecular features ( Table 1). Jejunum is the most frequent location for SBC in CD [2], an immune-mediated enteropathy induced by dietary gluten in genetically susceptible individuals [4]. CD-SBC exhibit a high frequency of microsatellite instability (MSI), increased tumour infiltrating T lymphocytes (TIL), a glandular histotype and intestinal phenotype [2,[5][6][7].…”

“…Jejunum is the most frequent location for SBC in CD [2], an immune-mediated enteropathy induced by dietary gluten in genetically susceptible individuals [4]. CD-SBC exhibit a high frequency of microsatellite instability (MSI), increased tumour infiltrating T lymphocytes (TIL), a glandular histotype and intestinal phenotype [2,[5][6][7]. On the other hand, SBC often localise in the inflamed ileum in CrD [2,8], a form of relapsing transmural inflammatory bowel disease due to an abnormal immune response to commensal microbiota [9].…”

“…CD-SBC exhibit a high frequency of microsatellite instability (MSI), increased tumour infiltrating T lymphocytes (TIL), a glandular histotype and intestinal phenotype [2,[5][6][7]. On the other hand, SBC often localise in the inflamed ileum in CrD [2,8], a form of relapsing transmural inflammatory bowel disease due to an abnormal immune response to commensal microbiota [9]. Most CrD-SBC are microsatellite stable, have low TILs and often show a non-glandular histotype coupled with a non-intestinal phenotype [2,7,8,[10][11][12].…”

“…management of CrD over the last two decades. Sporadic SBC (spo-SBC) patients generally have a higher median age at diagnosis -between 56.5 and 72.1 years-in comparison to both CD-SBC and CrD-SBC [2,5,5,10,24,27,29]. Risk factors for CD-SBC and CrD-SBC have not thoroughly investigated.…”