TY - JOUR
T1 - Small Bowel Carcinomas in Coeliac or Crohn's Disease
T2 - Clinico-pathological, Molecular, and Prognostic Features. A Study From the Small Bowel Cancer Italian Consortium
AU - Vanoli, Alessandro
AU - Di Sabatino, Antonio
AU - Furlan, Daniela
AU - Klersy, Catherine
AU - Grillo, Federica
AU - Fiocca, Roberto
AU - Mescoli, Claudia
AU - Rugge, Massimo
AU - Nesi, Gabriella
AU - Fociani, Paolo
AU - Sampietro, Gianluca
AU - Ardizzone, Sandro
AU - Luinetti, Ombretta
AU - Calabrò, Antonio
AU - Tonelli, Francesco
AU - Volta, Umberto
AU - Santini, Donatella
AU - Caio, Giacomo
AU - Giuffrida, Paolo
AU - Elli, Luca
AU - Ferrero, Stefano
AU - Latella, Giovanni
AU - Ciardi, Antonio
AU - Caronna, Roberto
AU - Solina, Gaspare
AU - Rizzo, Aroldo
AU - Ciacci, Carolina
AU - D'Armiento, Francesco P
AU - Salemme, Marianna
AU - Villanacci, Vincenzo
AU - Cannizzaro, Renato
AU - Canzonieri, Vincenzo
AU - Reggiani Bonetti, Luca
AU - Biancone, Livia
AU - Monteleone, Giovanni
AU - Orlandi, Augusto
AU - Santeusanio, Giuseppe
AU - Macciomei, Maria C
AU - D'Incà, Renata
AU - Perfetti, Vittorio
AU - Sandri, Giancarlo
AU - Silano, Marco
AU - Florena, Ada M
AU - Giannone, Antonino G
AU - Papi, Claudio
AU - Coppola, Luigi
AU - Usai, Paolo
AU - Maccioni, Antonio
AU - Astegiano, Marco
AU - Migliora, Paola
AU - Manca, Rachele
AU - Martino, Michele
AU - Trapani, Davide
AU - Cerutti, Roberta
AU - Alberizzi, Paola
AU - Riboni, Roberta
AU - Sessa, Fausto
AU - Paulli, Marco
AU - Solcia, Enrico
AU - Corazza, Gino R
PY - 2017/8/1
Y1 - 2017/8/1
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.1093/ecco-jcc/jjx031
DO - 10.1093/ecco-jcc/jjx031
M3 - Article
C2 - 28333239
VL - 11
SP - 942
EP - 953
JO - Journal of Crohn's and Colitis
JF - Journal of Crohn's and Colitis
SN - 1873-9946
IS - 8
ER -