P279 Crohn’s disease-associated small bowel carcinomas show distinctive histologic and phenotypic features: an Italian multicentric study
A. Di Sabatino*1, A. Vanoli2, F. Grillo3, C. Mescoli4, G. Nesi5, P. Giuffrida1, C. Papi6, O. Luinetti2, G. Sampietro7, G. Latella8, P. Fociani9, F. Tonelli5, R. Cannizzaro10, L. Coppola6, R. D’Incà4, G. Monteleone11, L. Biancone11, G. Solina12, V. Villanacci13, M. Martino1, A. Orlandi11, A. Rizzo12, M. Salemme13, M. Astegiano14, P. Migliora14, M. Rugge4, R. Fiocca3, G.R. Corazza1, E. Solcia2
1Fondazione IRCCS Policlinico San Matteo, University of Pavia, First Department of Medicine, Pavia, Italy, 2Fondazione IRCCS Policlinico San Matteo, University of Pavia, Department of Molecular Medicine, Pavia, Italy, 3Azienda Ospedaliera Universitaria San Martino, Genova, Italy, 4Azienda Ospedaliera di Padova, Padova, Italy, 5Azienda Ospedaliera Universitaria Careggi, Firenze, Italy, 6Azienda Ospedaliera San Filippo Neri, Roma, Italy, 7Luigi Sacco University Hospital, Surgery Division, Department of Clinical Sciences, Milan, Italy, 8Ospedale San Salvatore, L’Aquila, Italy, 9Luigi Sacco University Hospital, Chair of Pathology, Milan, Italy, 10Centro di Riferimento Oncologico, Aviano, Italy, 11Policlinico Tor Vergata, Roma, Italy, 12Ospedale V. Cervello, Palermo, Italy, 13Spedali Civili di Brescia, Brescia, Italy, 14Azienda Ospedaliera Universitaria Città della Salute e della Scienza, Torino, Italy
Although the small intestine accounts for 75% of the length of the gastrointestinal tract, non-ampullary small bowel carcinoma (SBC) is a remarkably rare tumour in the general population. Crohn’s disease (CD) is associated with an increased risk of development of SBC. Histomorphology and phenotype of CD-associated SBC (CD-SBC) have, however, not been thoroughly examined.
We evaluated histologically 25 cases of CD-associated SBC (CD-SBC) (median age 59 yr, range 33–84) in comparison to 24 sporadic cases (median age 65 yr, range 27–88). Immunoreactions for intestinal (CDX2, CD10, and CK20), gastric (MUC5AC and MUC6), and pancreatobiliary (CK7) markers, mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6), p53 and HER2 were performed. HER2 gene amplification was also investigated by FISH testing in cases with HER2 membranous reactivity.
CD-SBCs were frequently characterised by high-grade and/or diffuse histology. CK7 was expressed with significantly (p < 0.005) higher frequency in CD-SBCs (64%) in comparison to sporadic ones (17%). MUC5AC was detected with higher, though not significant, frequency in CD-SBCs (48%) in comparison to sporadic cases (21%). On the contrary, CDX2 and CK20 expression was significantly (p < 0.05) less frequent in CD-SBCs (both 36%) in comparison to sporadic SBCs (71% and 79%, respectively). CD10 was detected with lower, though not significant, frequency in CD-SBCs (16%) in comparison to sporadic SBCs (42%). There was no difference between CD-SBCs and sporadic cases regarding MUC6 and p53. Three CD-SBCs and 4 sporadic cases lacked both MLH1 and PMS2. HER2 amplification was observed in 2 out of 25 CD-SBCs. The 10-yr survival was lower in CD-SBCs (27%) than in sporadic cases (48%).
Compared with sporadic SBCs, CD-SBCs had several distinguishing histologic and immunophenotypic features, in particular, the gastric and, possibly, pancreatobiliary differentiation. The reduced expression of CDX2, as well as the phenotypic features, might explain, in part, the poorer prognosis of CD-SBCs. FISH testing made the 2 CD patients with HER2 amplification eligible for treatment with trastuzumab.