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

Heby, Margareta LU ; Lundgren, Sebastian LU ; Nodin, Björn LU ; Elebro, Jacob LU ; Eberhard, Jakob LU and Jirström, Karin LU (2018) In Journal of Translational Medicine 16(1).
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... (More)

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 Malmö 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.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Adjuvant therapy, Immunohistochemistry, MMR, Periampullary adenocarcinoma, TMA
in
Journal of Translational Medicine
volume
16
issue
1
article number
66
publisher
BioMed Central (BMC)
external identifiers
  • pmid:29540182
  • scopus:85043767594
ISSN
1479-5876
DOI
10.1186/s12967-018-1444-4
language
English
LU publication?
yes
id
2e81a9aa-4767-47cc-989c-da72db704204
date added to LUP
2018-03-26 13:48:27
date last changed
2021-10-06 05:44:50
@article{2e81a9aa-4767-47cc-989c-da72db704204,
  abstract     = {<p>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 Malmö 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 (p<sub>interaction</sub>=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.</p>},
  author       = {Heby, Margareta and Lundgren, Sebastian and Nodin, Björn and Elebro, Jacob and Eberhard, Jakob and Jirström, Karin},
  issn         = {1479-5876},
  language     = {eng},
  month        = {03},
  number       = {1},
  publisher    = {BioMed Central (BMC)},
  series       = {Journal of Translational Medicine},
  title        = {Relationship between mismatch repair immunophenotype and long-term survival in patients with resected periampullary adenocarcinoma},
  url          = {http://dx.doi.org/10.1186/s12967-018-1444-4},
  doi          = {10.1186/s12967-018-1444-4},
  volume       = {16},
  year         = {2018},
}