Background: There are different methods of categorization of Ampullary Adenocarcinomas’ (AACs) histological subtypes, as they represents Ampullary Adenocarcinomas (AACs) are an heterogeneous group of tumors and there are different methods of categorization of histological subtypes. The Hhistologicaly phenotype based on immunohistochemistry (IHC) of caudal-type homeodomain transcription factor 2 (CDX2) and Cytokeratins (CK7 and CK20) staining has been tested in order to identify three most important relevant sub-classes of AACs: Intestinal (INT), Pancreato-Biliary (PB) and Mixed-Type (MT). The identification of MT tumor is often difficult with the conventional histology and its clinical outcome is unclear. This study aims to identify only two subtypes in AACs samples, using an IHC score based-on CDX2, CK7 and CK20 evaluation. Methods: We arranged on TMA platform Ttissue samples from 20 patients with resected AACs were arranged on TMA platform and obtained their classification classified byaccording to histology and IHC expression of CDX2, CK7 and CK 20. We obtain 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 of expression (1=weak; 2=middle and 3=strong). A global score (GS) for each tumor was obtained by depending on the contribution of each marker. The MT tumors were located into INT or PB group on the basis ofaccording to the predominant immune-molecular phenotype. The overall survival values rates of patients with INT and PB tumors patients were obtained withby Kaplan-Meyer methods. Results: Histological parameters defined AAC subtype samples 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 INT and PB group, respectively. The mean value of GS was 9.5 (range 4-16). All INT samples had presented a GS over the mean, while all PB samples had a global score under the mean (p=0.0011). In pParticularly, the INT samples weare identified by an higher expression of CDX2 and CK20, while PB samples showed higher expression of CK7 and negative expression of CK20 (p=0.0008). The Overall Survival rate (OS) of patients with molecular INT intestinal histomolecular phenotype (INT) vs PB phenotype showed significant differences (85.7 vs 20.3 months, HR, 8.39; 95% CI, 1.38 to 18.90; p=0.0152). Conclusions: The combination of Hhistopathological and molecular criteria combination can define clinically relevant histomolecular phenotypes of AACs which could potentially represent distinct different diseases with relative different prognosis and significant implications for the current therapeutic strategies.
THE IMMUNOHISTOCHEMICAL SCORE OF CDX2, CK7 AND CK 20 CAN IDENTIFY PATHOLOGICAL SUBTYPES OF AMPULLARY ADENOCARCINOMAS AND THEIR PROGNOSIS
Palmeri M;Funel N;Furbetta N;Di Franco G;Guadagni S;Gianardi D;Bianchini M;Falcone A;Di Candio G;Del Chiaro M;Morelli L
2019-01-01
Abstract
Background: There are different methods of categorization of Ampullary Adenocarcinomas’ (AACs) histological subtypes, as they represents Ampullary Adenocarcinomas (AACs) are an heterogeneous group of tumors and there are different methods of categorization of histological subtypes. The Hhistologicaly phenotype based on immunohistochemistry (IHC) of caudal-type homeodomain transcription factor 2 (CDX2) and Cytokeratins (CK7 and CK20) staining has been tested in order to identify three most important relevant sub-classes of AACs: Intestinal (INT), Pancreato-Biliary (PB) and Mixed-Type (MT). The identification of MT tumor is often difficult with the conventional histology and its clinical outcome is unclear. This study aims to identify only two subtypes in AACs samples, using an IHC score based-on CDX2, CK7 and CK20 evaluation. Methods: We arranged on TMA platform Ttissue samples from 20 patients with resected AACs were arranged on TMA platform and obtained their classification classified byaccording to histology and IHC expression of CDX2, CK7 and CK 20. We obtain 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 of expression (1=weak; 2=middle and 3=strong). A global score (GS) for each tumor was obtained by depending on the contribution of each marker. The MT tumors were located into INT or PB group on the basis ofaccording to the predominant immune-molecular phenotype. The overall survival values rates of patients with INT and PB tumors patients were obtained withby Kaplan-Meyer methods. Results: Histological parameters defined AAC subtype samples 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 INT and PB group, respectively. The mean value of GS was 9.5 (range 4-16). All INT samples had presented a GS over the mean, while all PB samples had a global score under the mean (p=0.0011). In pParticularly, the INT samples weare identified by an higher expression of CDX2 and CK20, while PB samples showed higher expression of CK7 and negative expression of CK20 (p=0.0008). The Overall Survival rate (OS) of patients with molecular INT intestinal histomolecular phenotype (INT) vs PB phenotype showed significant differences (85.7 vs 20.3 months, HR, 8.39; 95% CI, 1.38 to 18.90; p=0.0152). Conclusions: The combination of Hhistopathological and molecular criteria combination can define clinically relevant histomolecular phenotypes of AACs which could potentially represent distinct different diseases with relative different prognosis and significant implications for the current therapeutic strategies.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
