Published online Nov 21, 2020. doi: 10.3748/wjg.v26.i43.6822
Peer-review started: May 29, 2020
First decision: June 12, 2020
Revised: June 24, 2020
Accepted: August 27, 2020
Article in press: August 27, 2020
Published online: November 21, 2020
Processing time: 175 Days and 2.9 Hours
Ampullary adenocarcinomas (AACs) are heterogeneous tumors currently classified into the three most important sub-classes (SC): Intestinal (INT), Pancreato-Biliary (PB) and Mixed-Type (MT). The different subgroups have similar clinical presentation and are treated by pancreatoduodenectomy with curative intent; however, they have different responses to specific chemotherapeutics, with different prognoses.
Conventional histology does not allow a definitive identification of the three subgroups.
In this study using an immunohistochemical (IHC) score based on CDX2, CK7 and CK20 evaluation through three tissue microarray platforms, we identified two clinically relevant histo-molecular sub-phenotypes of AACs.
Tissue samples from 21 patients who had undergone AAC resection were arranged on three tissue microarray platforms and were classified by histology and IHC expression of CDX2, CK7 and CK20. An IHC score was obtained for each marker summing the number of positive cells (0 = no stained cells; 1 < 25%; 2 < 50% and 3 > 50%) and their intensity (1 = weak; 2 = moderate and 3 = strong). A global score (GS) was then obtained summing the IHC scores of each marker. The MT tumors were re-located to either the INT or PB group on the basis of the predominant immune-molecular phenotype, identifying only two AACs subtypes. The overall survival of INT and PB patients was obtained by Kaplan-Meier methods.
Histological parameters defined the AACs subtypes as follows: 15% INT, 45%PB and 40% MT. Using the IHC expression and the GS, 75% and 25% of MT samples were assigned to the INT and PB group, respectively. The mean value of GS was 9.5 (range 4-16). All INT samples had a GS above the average, while all PB sample had a GS below the average (P = 0.0011). In particular, the INT samples were identified by high expression of CDX2 and CK20, while PB samples showed high expression of CK7 and negative expression of CK20 (P = 0.0008). The overall survival analysis was statistically significantly better for INT than PB patients (85.7 vs 20.3 mo, HR: 8.39; 95%CI: 1.38 to 18.90; P = 0.0152).
The combination of histopathological and molecular criteria enables the definition of only two clinically relevant histo-molecular phenotypes of AACs that potentially represent distinct disorders with different management and chemotherapeutic strategies.
A preoperative biopsy of the ampulla could provide a AACs subtype classification, allowing the tailoring of oncological treatment and planning the extension of surgical resection.