Relationship between mismatch repair immunophenotype and long-term survival in patients with resected periampullary adenocarcinoma

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title = "Relationship between mismatch repair immunophenotype and long-term survival in patients with resected periampullary adenocarcinoma",
abstract = "Background: Periampullary adenocarcinomas, including pancreatic cancer, are a heterogeneous group of tumors with poor prognosis, where classification into intestinal type (I-type) or pancreatobiliary type (PB-type) is a relevant prognostic factor. The clinical significance of deficient mismatch repair (dMMR) in periampullary adenocarcinoma is comparatively unexplored. Herein, we examined the associations of MMR immunophenotype with long-term survival in patients with resected periampullary adenocarcinoma, with particular reference to morphology and adjuvant treatment response. Methods: MMR protein expression was assessed by immunohistochemistry on tissue microarrays with primary tumors from a retrospective cohort of 175 patients with periampullary adenocarcinoma treated with pancreaticoduodenectomy during 2001-2011 in Malm{\"o} and Lund University Hospitals, Sweden. Cox proportional hazards models were applied to calculate hazard ratios (HR) and 95{\%} confidence intervals (CI). Results: After a mean follow-up of 46.5 (1.9-185.1) months, 35 patients (20.3{\%}) were alive, 24 with I-type and 11 with PB-type tumors. MMR protein expression could be evaluated in 172 cases, in which dMMR was denoted in 20 (11.6{\%}) cases, 13/63 (20.6{\%}) in I-type and 7/109 (6.4{\%}) in PB-type tumors. dMMR was associated with a significantly prolonged overall survival in the entire cohort (HR=0.28, 95{\%} CI 0.13-0.57), and in I-type tumors (HR=0.20, 95{\%} CI 0.06-0.68), however not independent of conventional prognostic factors. In PB-type tumors, dMMR was not prognostic, but there was a significant negative interaction between dMMR and adjuvant treatment (pinteraction=0.015). Conclusions: dMMR is more frequent in I-type compared to PB-type periampullary adenocarcinoma, and is a prognostic factor for long-term survival only in the former. The finding of the small number of PB-type tumors with dMMR potentially lacking benefit from adjuvant chemotherapy is however noteworthy and merits further validation.",
keywords = "Adjuvant therapy, Immunohistochemistry, MMR, Periampullary adenocarcinoma, TMA",
author = "Margareta Heby and Sebastian Lundgren and Bj{\"o}rn Nodin and Jacob Elebro and Jakob Eberhard and Karin Jirstr{\"o}m",
year = "2018",
month = "3",
day = "14",
doi = "10.1186/s12967-018-1444-4",
language = "English",
volume = "16",
journal = "Journal of Translational Medicine",
issn = "1479-5876",
publisher = "BioMed Central",
number = "1",