TY - JOUR
T1 - Performance and prognostic utility of the 92-gene assay in the molecular subclassification of ampullary adenocarcinoma
AU - Overman, Michael J.
AU - Soifer, Harris S.
AU - Schueneman, Aaron Joel
AU - Ensor, Joe
AU - Adsay, Volkan
AU - Saka, Burcu
AU - Neishaboori, Nastaran
AU - Wolff, Robert A.
AU - Wang, Huamin
AU - Schnabel, Catherine A.
AU - Varadhachary, Gauri
N1 - Funding Information:
Authors HSS and CAS are employees at Biotheranostics, Inc. MJO, HW, and GV have received research funding from Biotheranostics, Inc. All remaining authors declare that they have no competing interest.
Funding Information:
This work was supported by the Kavanagh Family Foundation to (M.O.), Institute Merieux research grant to (M.O, G.V. and H.W.), and a Biotheranostics research grant to (M.O., G.V. and H.W.).
Publisher Copyright:
© 2016 The Author(s).
PY - 2016/8/22
Y1 - 2016/8/22
N2 - Background: Ampullary 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. Methods: In 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. Results: The 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). Conclusions: Prognostic 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.
AB - Background: Ampullary 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. Methods: In 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. Results: The 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). Conclusions: Prognostic 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.
KW - 92-gene assay
KW - Adenocarcinoma
KW - Ampullary
KW - Biomarker
KW - Gene expression profiling
KW - Prognostic
KW - Subclassification
UR - http://www.scopus.com/inward/record.url?scp=84983036505&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84983036505&partnerID=8YFLogxK
U2 - 10.1186/s12885-016-2677-3
DO - 10.1186/s12885-016-2677-3
M3 - Article
C2 - 27549176
AN - SCOPUS:84983036505
SN - 1471-2407
VL - 16
JO - BMC Cancer
JF - BMC Cancer
IS - 1
M1 - 668
ER -