TY - JOUR
T1 - Comprehensive characterisation of pancreatic ductal adenocarcinoma with microsatellite instability
T2 - Histology, molecular pathology and clinical implications
AU - Luchini, Claudio
AU - Brosens, Lodewijk A.A.
AU - Wood, Laura D.
AU - Chatterjee, Deyali
AU - Shin, Jae Il
AU - Sciammarella, Concetta
AU - Fiadone, Giulia
AU - Malleo, Giuseppe
AU - Salvia, Roberto
AU - Kryklyva, Valentyna
AU - Piredda, Maria L.
AU - Cheng, Liang
AU - Lawlor, Rita T.
AU - Adsay, Volkan
AU - Scarpa, Aldo
N1 - Funding Information:
Funding This study is supported by Associazione Italiana Ricerca sul Cancro (AIRC 5x1000 n. 12182) and Fondazione Cariverona: Oncology Biobank Project ’Antonio Schiavi’ (prot. 203885/2017). VK is supported by the Dutch Cancer Society (KWF grant 2016, 10289).
Publisher Copyright:
©
PY - 2021/1/1
Y1 - 2021/1/1
N2 - Objective Recently, tumours with microsatellite instability (MSI)/defective DNA mismatch repair (dMMR) have gained considerable interest due to the success of immunotherapy in this molecular setting. Here, we aim to clarify clinical-pathological and/or molecular features of this tumour subgroup through a systematic review coupled with a comparative analysis with existing databases, also providing indications for a correct approach to the clinical identification of MSI/dMMR pancreatic ductal adenocarcinoma (PDAC). Design PubMed, SCOPUS and Embase were searched for studies reporting data on MSI/dMMR in PDAC up to 30 November 2019. Histological and molecular data of MSI/dMMR PDAC were compared with non-MSI/dMMR PDAC and with PDAC reference cohorts (including SEER database and The Cancer Genome Atlas Research Network - TCGA project). Results Overall, 34 studies with 8323 patients with PDAC were included in the systematic review. MSI/dMMR demonstrated a very low prevalence in PDAC (around 1%-2%). Compared with conventional PDAC, MSI/dMMR PDAC resulted strongly associated with medullary and mucinous/colloid histology (p<0.01) and with a KRAS/TP53 wild-type molecular background (p<0.01), with more common JAK genes mutations. Data on survival are still unclear. Conclusion PDAC showing typical medullary or mucinous/colloid histology should be routinely examined for MSI/dMMR status using specific tests (immunohistochemistry, followed by MSI-PCR in cases with doubtful results). Next-generation sequencing (NGS) should be adopted either where there is limited tissue or as part of NGS tumour profiling in the context of precision oncology, acknowledging that conventional histology of PDAC may rarely harbour MSI/dMMR.
AB - Objective Recently, tumours with microsatellite instability (MSI)/defective DNA mismatch repair (dMMR) have gained considerable interest due to the success of immunotherapy in this molecular setting. Here, we aim to clarify clinical-pathological and/or molecular features of this tumour subgroup through a systematic review coupled with a comparative analysis with existing databases, also providing indications for a correct approach to the clinical identification of MSI/dMMR pancreatic ductal adenocarcinoma (PDAC). Design PubMed, SCOPUS and Embase were searched for studies reporting data on MSI/dMMR in PDAC up to 30 November 2019. Histological and molecular data of MSI/dMMR PDAC were compared with non-MSI/dMMR PDAC and with PDAC reference cohorts (including SEER database and The Cancer Genome Atlas Research Network - TCGA project). Results Overall, 34 studies with 8323 patients with PDAC were included in the systematic review. MSI/dMMR demonstrated a very low prevalence in PDAC (around 1%-2%). Compared with conventional PDAC, MSI/dMMR PDAC resulted strongly associated with medullary and mucinous/colloid histology (p<0.01) and with a KRAS/TP53 wild-type molecular background (p<0.01), with more common JAK genes mutations. Data on survival are still unclear. Conclusion PDAC showing typical medullary or mucinous/colloid histology should be routinely examined for MSI/dMMR status using specific tests (immunohistochemistry, followed by MSI-PCR in cases with doubtful results). Next-generation sequencing (NGS) should be adopted either where there is limited tissue or as part of NGS tumour profiling in the context of precision oncology, acknowledging that conventional histology of PDAC may rarely harbour MSI/dMMR.
KW - immunotherapy
KW - microsatellite instability
KW - pancreatic cancer
UR - http://www.scopus.com/inward/record.url?scp=85084314935&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85084314935&partnerID=8YFLogxK
U2 - 10.1136/gutjnl-2020-320726
DO - 10.1136/gutjnl-2020-320726
M3 - Article
C2 - 32350089
AN - SCOPUS:85084314935
SN - 0017-5749
VL - 70
SP - 148
EP - 156
JO - Gut
JF - Gut
IS - 1
ER -