학술논문
Mismatch Repair Deficiency in Biliary Tract Cancer: Prognostic Implications and Correlation with Histology.
Document Type
Article
Author
Vivaldi, Caterina; Genovesi, Virginia; Ugolini, Clara; Bernardini, Laura; Casadei-Gardini, Andrea; Formica, Vincenzo; Salani, Francesca; Orsi, Giulia; Massa, Valentina; Cacciato-Insilla, Andrea; Caccese, Miriam; Cesario, Silvia; Andrikou, Kalliopi; Graziani, Jessica; Campani, Daniela; Vasile, Enrico; Fontanini, Gabriella; Fornaro, Lorenzo; Masi, Gianluca
Source
Subject
*RESEARCH
*IMMUNOHISTOCHEMISTRY
*MULTIVARIATE analysis
*CANCER relapse
*RETROSPECTIVE studies
*ACQUISITION of data
*METASTASIS
*DISEASE incidence
*PROTEIN deficiency
*RISK assessment
*COMPARATIVE studies
*SURGICAL margin
*SYMPTOMS
*BILIARY tract
*MEDICAL records
*SURVIVAL analysis (Biometry)
*DESCRIPTIVE statistics
*TUMOR markers
*DNA repair
*STATISTICAL correlation
*LONGITUDINAL method
*DISEASE risk factors
BILE duct tumors
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Language
ISSN
0030-2414
Abstract
Introduction: Mismatch repair (MMR) deficiency represents a biomarker and therapeutic target in various neoplasms, but its role in biliary tract cancers (BTCs) remains misunderstood. Methods: MMR status was retrospectively assessed using immunohistochemistry in 163-BTCs patients. We identified MMR proficiency (pMMR)/deficiency (dMMR) according to the loss of MMR proteins (MLH1, PMS2, MSH2, MSH6). The primary objective of the study was to assess the incidence of dMMR in BTCs; the secondary purpose was to explore its association with prognosis and clinical features. Results: dMMR was recorded in 9 patients, and it was strongly associated with mucinous histology (p < 0.01). Regarding the prognostic effect, in 122-radically resected patients, disease-free survival (DFS) resulted significantly shorter in dMMR patients compared to pMMR patients (10.7 vs. 31.3 months, p = 0.025) and so did nodal status (48.2 vs. 15.3 months in N0 vs. N+) (p < 0.01). Moreover, dMMR confirmed its prognostic role in terms of DFS at multivariate analysis (p = 0.03), together with nodal status (p = 0.01), and resection margin (p = 0.03). In 103 M+ patients (encompassing 41 metastatic de novo and 62 recurred after surgery patients) there were not differences between dMMR and pMMR regarding survival analyses. Conclusions: dMMR status is strongly correlated with mucinous histology and represents an independent prognostic factor in terms of disease relapse in patients with resected BTC. Implications for Practice: MMR may play an independent role in promoting an aggressive behaviour in patients with radically resected BTC. These results could be useful in improving the selection of patients after resection and, above all, should justify the evaluation of MMR status as a therapeutic target in BTC, especially in patients with atypical histology. [ABSTRACT FROM AUTHOR]