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. 2018 Oct;9(5):820-827.
doi: 10.21037/jgo.2018.05.03.

KRAS, NRAS and BRAF analysis of ampullary adenocarcinoma classified using CK7, CK20, MUC1 and MUC2

Marwa Ferchichi  1   2 , Raja Jouini  2 , Imen Ayari  1   2 , Wafa Koubaa  2 , Aschraf Chadli-Debbiche  2 , Ehsen BenBrahim  2
Affiliations

KRAS, NRAS and BRAF analysis of ampullary adenocarcinoma classified using CK7, CK20, MUC1 and MUC2

Marwa Ferchichi et al. J Gastrointest Oncol. 2018 Oct.

Abstract

Background: Ampullary carcinomas are rare and dominated by adenocarcinomas. They account for only 0.5% of all gastrointestinal malignancies. Ampullary adenocarcinoma (AAC) with pancreaticobiliary (PB) histology has a worse outcome than that with intestinal (IT) histology. The mixed subtype contains the two epitheliums. This subclassification remains a challenge for pathologists and induces a reasonable level of disagreement. Genetic features of these subtypes are unclear. In this study, we aimed to reclassify AAC cases then to evaluate differences in prognostic, pathological and molecular parameters including mutational status of three oncogenes between these subtypes.

Methods: AACs from 21 Tunisian patients were used in this study. Reclassification was made based on histology and immunohistochemistry (IHC) using CK7, CK20, MUC1 and MUC2. Mutational analysis included the pyrosequencing of KRAS, NRAS and BRAF.

Results: Fifteen cases were PB subtype, 2 cases were IT subtype and 4 cases were mixed subtype. CK20 and MUC2 were associated with N stage, MUC1 and histomolecular subtype with T stage. Nine cases were mutated and 12 were wild-type. Eight cases were KRAS mutated (5 G12D and 3 G12V). Only 1 case was NRAS mutated (G12D). No BRAF mutation was found. Genetic alterations didn't influence prognostic factors.

Conclusions: We validate the prognostic utility of AAC histomolecular classification.

Keywords: Ampullary adenocarcinoma (AAC); RAF; RAS; apomucin (MUC); cytokeratin (CK).

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Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Pancreatobiliary subtype(hematoxylin-eosin staining) (A) classified by histology. This case expressed typically MUC1 in IHC (B) like pancreatic acini used as control (C) (magnification: A, ×200; B, ×400; C, ×200). The arrow shows a vascular emboli.
Figure 2
Figure 2
Mixed subtype (A) (hematoxylin-eosin stain) expressed MUC1 (B) and MUC2 (C) in IHC (magnification: A, ×200; B, ×400; C, ×200).
See this image and copyright information in PMC

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