Clinical impact of ampulla of Vater cancer subtype classification based on immunohistochemical staining

Abstract

Background The histological subtype is an important prognostic factor for ampulla of Vater (AoV) cancer. This study proposes a classification system for the histological subtyping of AoV cancer based on immunohistochemical (IHC) staining and its prognostic significance. Methods Seventy-five AoV cancers were analyzed for cytokeratin 7 (CK7), CK20, and causal-type homeobox transcription factor 2 (CDX2) expression by IHC staining. We differentiated the subtypes (INT, intestinal; PB, pancreatobiliary; MIX, mixed; NOS, not otherwise specified) into classification I: CK7/CK20, classification II: CK7/CK20 or CDX2, classification III: CK7/CDX2 and examined their associations with clinicopathological factors. Results Classifications I, II, and III subtypes were INT (7, 10, and 10 cases), PB (43, 37, and 38 cases), MIX (13, 19, and 18 cases), and NOS (12, 9, and 9 cases). Significant differences in disease-free survival among the subtypes were observed in classifications II and III using CDX2; the PB and NOS subtype exhibited shorter survival time compared with INT subtype. In classification III, an association was revealed between advanced T/N stage, poor differentiation, lymphovascular invasion (LVI), the PB and NOS subtypes, and recurrence risk. In classification III, the subtypes differed significantly in T/N stage and LVI. Patients with the PB subtype had advanced T and N stages and a higher incidence of LVI. Conclusions Classification using CDX2 revealed subtypes with distinct prognostic significance. Combining CK7 and CDX2 or adding CDX2 to CK7/CK20 is useful for distinguishing subtypes, predicting disease outcomes, and impacting the clinical management of patients with AoV cancer.

Prognostic Impact of Mucin Expression in Curatively Resected Ampulla of Vater Cancer

“…Despite the inherent limitations of a single-institution study conducted by a single researcher, our findings offer valuable insights into the clinicopathological variations in mucin expression among rare AoV cancer cases, irrespective of the histological subtype. Previous studies, including ours, have established that CK7, CK20, and CDX2 are sufficient markers for subtyping [10]. Therefore, in this study, we did not explore the association between mucin expression and histological subtype.…”

“…The histological type of ampullary adenocarcinoma has been independently associated with patient survival and plays an important role in guiding the selection of adjuvant regimens [ 5 , 6 , 7 ]. Recent reports, including our previous study, have suggested that subtyping using immunohistochemical (IHC) staining alone could have significant clinical implications [ 8 , 9 , 10 ]. Investigating a combination of different markers and their expression may provide a more comprehensive understanding of tumor biology, which can aid in determining prognosis and tailoring treatment strategies for individual patients.…”