TY - JOUR
T1 - Clinical and Genetic Implications of DNA Mismatch Repair Deficiency in Biliary Tract Cancers Associated with Lynch Syndrome
AU - Cloyd, Jordan M.
AU - Chun, Yun Shin
AU - Ikoma, Naruhiko
AU - Vauthey, Jean Nicolas
AU - Aloia, Tlhomas A.
AU - Cuddy, Amanda
AU - Rodriguez-Bigas, Miguel A.
AU - Nancy You, Y.
N1 - Publisher Copyright:
© 2017, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2018/3/1
Y1 - 2018/3/1
N2 - Purpose: Patients with Lynch syndrome (LS) have a significantly elevated lifetime risk of developing biliary tract cancers (BTCs) compared to the general population. However, few studies have characterized the clinical characteristics, genetic features, or long-term outcomes of mismatch-repair deficient (dMMR) cholangiocarcinomas associated with LS. Methods: A retrospective review of a prospectively maintained Familial High-Risk GI Cancer Clinic database identified all patients with BTCs evaluated from 2006 to 2016 who carried germline mutations in MLH1, MSH2, MSH6, or PMS2. Results: Eleven patients with BTCs were identified: four perihilar, four intrahepatic, one extrahepatic, one gallbladder, and one ampulla of Vater. All patients had underlying germline mutations and a personal history of a LS-associated malignancy, most commonly (63.3%) colorectal cancer. Ten (90.9%) patients were surgically explored, and margin negative resection was possible in seven (63.3%). Chemotherapy (90.9%) and/or chemoradiation (45.5%) was administered to most patients. Among the seven patients presenting with non-metastatic disease who underwent surgical resection with curative intent, the 5-year overall survival rate was 53.3%. The median overall survival for the four patients not treated with curative intent was 17.2 months. Conclusions: dMMR biliary tract cancers associated with LS are rare but long-term outcomes may be more favorable than contemporaneous cohorts of non-Lynch-associated cholangiocarcinomas. Given the emerging promise of immunotherapy for patients with dMMR malignancies, tumor testing for dMMR followed by confirmatory germline testing should be considered in patients with BTC and a personal history of other LS cancers.
AB - Purpose: Patients with Lynch syndrome (LS) have a significantly elevated lifetime risk of developing biliary tract cancers (BTCs) compared to the general population. However, few studies have characterized the clinical characteristics, genetic features, or long-term outcomes of mismatch-repair deficient (dMMR) cholangiocarcinomas associated with LS. Methods: A retrospective review of a prospectively maintained Familial High-Risk GI Cancer Clinic database identified all patients with BTCs evaluated from 2006 to 2016 who carried germline mutations in MLH1, MSH2, MSH6, or PMS2. Results: Eleven patients with BTCs were identified: four perihilar, four intrahepatic, one extrahepatic, one gallbladder, and one ampulla of Vater. All patients had underlying germline mutations and a personal history of a LS-associated malignancy, most commonly (63.3%) colorectal cancer. Ten (90.9%) patients were surgically explored, and margin negative resection was possible in seven (63.3%). Chemotherapy (90.9%) and/or chemoradiation (45.5%) was administered to most patients. Among the seven patients presenting with non-metastatic disease who underwent surgical resection with curative intent, the 5-year overall survival rate was 53.3%. The median overall survival for the four patients not treated with curative intent was 17.2 months. Conclusions: dMMR biliary tract cancers associated with LS are rare but long-term outcomes may be more favorable than contemporaneous cohorts of non-Lynch-associated cholangiocarcinomas. Given the emerging promise of immunotherapy for patients with dMMR malignancies, tumor testing for dMMR followed by confirmatory germline testing should be considered in patients with BTC and a personal history of other LS cancers.
KW - Biliary tract cancer
KW - Cholangiocarcinoma
KW - Hepatectomy
KW - Immunotherapy
KW - Lynch syndrome
KW - Microsatellite instability
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U2 - 10.1007/s12029-017-0040-9
DO - 10.1007/s12029-017-0040-9
M3 - Article
C2 - 29238914
AN - SCOPUS:85037971170
SN - 1941-6628
VL - 49
SP - 93
EP - 96
JO - Journal of Gastrointestinal Cancer
JF - Journal of Gastrointestinal Cancer
IS - 1
ER -