Small Bowel Carcinomas in Coeliac or Crohn's Disease: Clinico-pathological, Molecular, and Prognostic Features. A Study From the Small Bowel Cancer Italian Consortium.
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Vanoli Alessandro, Di Sabatino Antonio, Furlan Daniela, Klersy Catherine, Grillo Federica, Fiocca Roberto, Mescoli Claudia, Rugge Massimo, Nesi Gabriella, Fociani Paolo, Sampietro Gianluca, Ardizzone Sandro, Luinetti Ombretta, Calabrò Antonio, Tonelli Francesco, Volta Umberto, Santini Donatella, Caio Giacomo, Giuffrida Paolo, Elli Luca, Ferrero Stefano, Latella Giovanni, Ciardi Antonio, Caronna Roberto, Solina Gaspare, Rizzo Aroldo, Ciacci Carolina, D'Armiento Francesco P, Salemme Marianna, Villanacci Vincenzo, Cannizzaro Renato, Canzonieri Vincenzo, Reggiani Bonetti Luca, Biancone Livia, Monteleone Giovanni, Orlandi Augusto, Santeusanio Giuseppe, Macciomei Maria C, D'Incà Renata, Perfetti Vittorio, Sandri Giancarlo, Silano Marco, Florena Ada M, Giannone Antonino G, Papi Claudio, Coppola Luigi, Usai Paolo, Maccioni Antonio, Astegiano Marco, Migliora Paola, Manca Rachele, Martino Michele, Trapani Davide, Cerutti Roberta, Alberizzi Paola, Riboni Roberta, Sessa Fausto, Paulli Marco, Solcia Enrico, Corazza Gino R
Аннотация
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.