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 (MLH-1, PMS-2, MSH-2, MSH-6). 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 weren't differences between dMMR and pMMR regarding survival analyses. Discussion/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.

Mismatch Repair Deficiency in Biliary Tract Cancer: Prognostic Implications and Correlation with Histology

Vivaldi, Caterina;Genovesi, Virginia;Ugolini, Clara;Bernardini, Laura;Salani, Francesca;Massa, Valentina;Cacciato-Insilla, Andrea;Caccese, Miriam;Cesario, Silvia;Graziani, Jessica;Campani, Daniela;Fontanini, Gabriella;Masi, Gianluca
2024-01-01

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 (MLH-1, PMS-2, MSH-2, MSH-6). 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 weren't differences between dMMR and pMMR regarding survival analyses. Discussion/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.
2024
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
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/1231207
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 1
  • Scopus 0
  • ???jsp.display-item.citation.isi??? 1
social impact