Ampulla of Vater Carcinoma

Abstract

KRAS and TP53 mutations are negative predictors of survival in AVCs, regardless of histotype. Potentially actionable mutations in ERBB, WNT, and PI3K signaling pathway genes are present in 37.5% of all cases. These might be amenable to target therapy using available drugs like Everolimus in PI3K-mutated cases or compounds under active screening against ERBB and WNT signaling.

Ampulla of Vater carcinoma: Molecular landscape and clinical implications

“…A significant proportion of AVCs, ranging between 18% and 40%, presents a hybrid phenotype characterized by overlapping intestinal and pancreatobiliary features[ 28 , 29 ] and frequently by a nondistinctive immunohistochemistry (Figure 4 )[ 28 ]. These aspects partially explain the high interobserver variability among pathologists in classifying AVCs subtypes[ 15 , 16 , 28 ].…”

“…Chang et al[ 13 ] proposed a 2-marker panel, composed of CDX2 and MUC1, showing that the PB phenotype was associated with a poor prognosis. However, more recent studies questioning the accuracy and reproducibility of this method failed in identifying direct or significant prognostic correlations with the immunohistochemical patterns[ 15 , 16 ]. Notably, alterations in the “gastric” lineage marker MUC5AC have also been associated with poor outcome in AVCs, but further studies are needed to validate its prognostic role[ 15 ].…”

“…Recent advances in sequencing technologies have permitted the in-depth characterization of the AVC molecular profile, providing important insights for the comprehension of the biology of this malignancy[ 14 , 16 , 17 ]. Particularly, two different whole exome sequencing analyses for a total of 240 patients have refined the knowledge about the mutational landscape of AVCs[ 14 , 17 ].…”

“…The lack of a specific genetic signature for the histological types suggests the existence of common biological mechanisms in the development of ampullary carcinoma, highlighting the heterogeneity of AVCs from the morphological to the molecular levels. This further calls for a reconsideration of the utility of the histological classification, since the genetic landscape indicates the lack of a specific distinction corresponding to morphology[ 16 ].…”

“…Interestingly, ERBB2 amplification has been demonstrated in up 23% of cases[ 16 , 37 ]. In a recent report, it was observed in 13% of AVCs regardless of histological subtype and was virtually mutually exclusive with downstream mutations in KRAS / NRAS / BRAF , that are responsible for resistance of therapies targeting ERBB2 [ 37 ].…”