Abstract

Background: Ampullary cancer is of particular classificatory interest as it may arise either from the intestinal epithelium or the epithelium covering the pancreatobiliary ducts knows as Intestinal type (IT) and Pancreatobiliary type (PBT) respectively. These 2 histological subtypes have different clinical characteristics, in terms of disease stage, recurrence rates and survival. Immunohistochemical staining against specific differentiation markers, including cytokeratins 7 (CK7) and 20 (CK20), mucins 1 (MUC1) and 2 (MUC2), as well as caudal type homeodomain (CDX2) protein, has been proven to be a useful adjunct in determining the exact histological sub type, especially in cases of large or mixed type tumors. Material and Methods: During the study period (2018–2021), 15 consecutive patients with IT and 15 consecutive patients with PBT adenocarcinoma, based on H&E staining characteristics, were included in analysis. Data on clinical parameters, including age, gender, pre-operative assessment of disease stage, CA 19-9 serum levels and histopathological parameters including tumor size, pT stage, pN stage, LVI, PNI and differentiation were collected in a prospective manner from patients’ surgical and pathological records. IHC markers (CK7, CK20, CDX20 and MUC1) were analyzed on all histopathological blocks. Results: In our analysis, pT Stage, Tumor Stage, CA 19-9 (IU/mL), Tumor size (cm), PNI, MUC1, combination CK7/MUC1, CK20, CDX2, combination CK20/CDX2 were significantly associated with histological subtype. CDX2 expression was found to have highest diagnostic accuracy (96.7%) for histological subtype followed by, in decreasing frequency, high CA 19-9 (93.3%), MUC1 (90%) and CK20/CDX2 combination (90%) and CK20 (86.7%). CDX2 was the only marker that showed highest sensitivity (100%) and high specificity (93.3%) for predicting IT. MUC1 positivity was associated with PBT with highest sensitivity of 100% and high specificity of 80%. The combination of CK7/MUC1 showed 86.7% sensitivity and 80% specificity with 83.3% diagnostic accuracy to identify PBT tumor, whereas combination of CK20/CDX2 showed 100% sensitivity and 80% specificity with 90% diagnostic accuracy to identify IT tumor. Conclusion: CDX2 and MUC1 have a highest sensitivity (100%) and highest NPV (100%) for IT and PBT differentiation respectively. These immunohistochemical subtypes correlates well with the conventional histomorphological classification. A panel of IHC markers like CK20 and CDX2 together allows better identification of differentiation than the use of single markers alone.

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