Performance and prognostic utility of the 92-gene assay in the molecular subclassification of ampullary adenocarcinoma

Abstract

BackgroundAmpullary adenocarcinoma is a rare gastrointestinal cancer associated with diverse outcomes due to clinical and pathological heterogeneity. Standardized methods to better prognosticate and inform therapeutic selection for ampullary adenocarcinoma are needed. This study explored the novel use and potential prognostic utility of a 92-gene cancer classifier in ampullary adenocarcinomas.MethodsIn this prospectively-defined, blinded study of ampullary adenocarcinoma [N =54; stage T3 or higher (57 %); Grade III (44 %); Node positive (55 %)], the performance of a 92-gene classifier was examined to predict the ampullary subtype that was derived from histomorphological examination of resected ampullary samples. Outcome data for relapse-free survival (RFS) and overall survival (OS) were plotted to compare the prognostic utility of histological subtyping, histomolecular phenotyping, and the 92-gene classifier. Multivariate analysis was used to determine clinicopathological variables that were independently associated with overall survival.ResultsThe 92-gene classifier demonstrated sensitivities and specificities of 85 % [95 % CI, 66–94] and 68 % [95 % CI, 48–84] and 64 % [95 % CI, 46–79] and 88 % [95 % CI, 70–98] for the pancreaticobiliary and intestinal histological subtypes, respectively. For the 92-gene classifier, improved outcomes were observed for the intestine versus the pancreaticobiliary prediction (median OS 108.1 v 36.4 months; HR, 2.17; 95 % CI, 0.98 to 4.79; P = 0.05). Similar results were seen for ampullary adenocarcinoma stratification by histological subtype (P = 0.04) and histomolecular phenotype (P = 0.02). Within poorly differentiated ampullary adenocarcinomas only the 92-gene classifier demonstrated statistically significant differences in RFS and OS (P < 0.05).ConclusionsPrognostic stratification of ampullary adenocarcinoma was similar for the 92-gene classifier, histological subtype, and histomolecular phenotype. The 92-gene classifier provides an unbiased standardized molecular-based approach to stratify ampullary tumors.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2677-3) contains supplementary material, which is available to authorized users.

Increased expression of secreted frizzled related protein 1 (SFRP1) predicts ampullary adenocarcinoma recurrence

“…The present study provided a possible explanation regarding the interaction with different oncogenic pathways in ampullary adenocarcinoma. Ampullary adenocarcinoma is a heterogeneous cancer with intestinal and pancreaticobiliary subtypes 4 . Molecular signatures are utilised to group patients.…”

“…Molecular signatures are utilised to group patients. Patients with pancreaticobiliary subtypes have a worse prognosis than those with intestinal subtypes 3,4 . The pathologist at NCKUH did not recognise pancreaticobiliary Table 2.…”

Biomarkers for Early Cancer Diagnosis: Prospects for Success through the Lens of Tumor Genetics

“…Biomarker research may also benefit from ongoing efforts to subclassify existing tumor classes (i.e., based on tissue or organ of origin) into distinct molecular subtypes according to particular genetic alterations (e.g., refs. [56–58]). These more homogeneous subclasses differ in clinical behavior, encouraging the design of targeted therapies.…”

Ampullary adenocarcinoma: Defining predictors of survival and the impact of adjuvant therapy following surgical resection for stage I disease

“…Secondly, the NCDB does not provide information regarding recurrence, an important consideration when attempting to fully appreciate the appropriate utilization of adjuvant strategies for cancer patients. Finally, as high throughput molecular profiling of tumors is increasingly utilized, its potential prognostic and therapeutic implications will continue to evolve, likely eventually playing a role in this discussion which we cannot currently characterize …”