Histomolecular phenotypes and outcome in adenocarcinoma of the ampulla of vater

David K. Chang, Nigel B. Jamieson, Amber L. Johns, Christopher J. Scarlett, Marina Pajic, Angela Chou, Mark Pinese, Jeremy L. Humphris, Marc D. Jones, Christopher Toon, Adnan M. Nagrial, Lorraine A. Chantrill, Venessa T. Chin, Andreia V. Pinho, Ilse Rooman, Mark J. Cowley, Jianmin Wu, R. Scott Mead, Emily K. Colvin, Jaswinder S. Samra & 19 others Vincenzo Corbo, Claudio Bassi, Massimo Falconi, Rita T. Lawlor, Stefano Crippa, Nicola Sperandio, Samantha Bersani, Euan J. Dickson, Mohamed A A Mohamed, Karin A. Oien, Alan K. Foulis, Elizabeth A. Musgrove, Robert L. Sutherland, James G. Kench, C. Ross Carter, Anthony J. Gill, Aldo Scarpa, Colin J. McKay, Andrew V. Biankin

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Purpose: Individuals with adenocarcinoma of the ampulla of Vater demonstrate a broad range of outcomes, presumably because these cancers may arise from any one of the three epithelia that converge at that location. This variability poses challenges for clinical decision making and the development of novel therapeutic strategies. Patients and Methods: We assessed the potential clinical utility of histomolecular phenotypes defined using a combination of histopathology and protein expression (CDX2 and MUC1) in 208 patients from three independent cohorts who underwent surgical resection for adenocarcinoma of the ampulla of Vater. Results: Histologic subtype and CDX2 and MUC1 expression were significant prognostic variables. Patients with a histomolecular pancreaticobiliary phenotype (CDX2 negative, MUC1 positive) segregated into a poor prognostic group in the training (hazard ratio [HR], 3.34; 95% CI, 1.69 to 6.62; P < .001) and both validation cohorts (HR, 5.65; 95% CI, 2.77 to 11.5; P < .001 and HR, 2.78; 95% CI, 1.25 to 7.17; P = .0119) compared with histomolecular nonpancreaticobiliary carcinomas. Further stratification by lymph node (LN) status defined three clinically relevant subgroups: one, patients with histomolecular nonpancreaticobiliary (intestinal) carcinoma without LN metastases who had an excellent prognosis; two, those with histomolecular pancreaticobiliary carcinoma with LN metastases who had a poor outcome; and three, the remainder of patients (nonpancreaticobiliary, LN positive or pancreaticobiliary, LN negative) who had an intermediate outcome. Conclusion: Histopathologic and molecular criteria combine to define clinically relevant histomolecular phenotypes of adenocarcinoma of the ampulla of Vater and potentially represent distinct diseases with significant implications for current therapeutic strategies, the ability to interpret past clinical trials, and future trial design.

LanguageEnglish
Pages1348-1356
Number of pages9
JournalJournal of Clinical Oncology
Volume31
Issue number10
DOIs
Publication statusPublished - 1 Apr 2013
Externally publishedYes

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Ampulla of Vater
Adenocarcinoma
Lymph Nodes
Phenotype
Carcinoma
Neoplasm Metastasis
Epithelium
Clinical Trials
Therapeutics
Neoplasms

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Chang, D. K., Jamieson, N. B., Johns, A. L., Scarlett, C. J., Pajic, M., Chou, A., ... Biankin, A. V. (2013). Histomolecular phenotypes and outcome in adenocarcinoma of the ampulla of vater. Journal of Clinical Oncology, 31(10), 1348-1356. https://doi.org/10.1200/JCO.2012.46.8868
Chang, David K. ; Jamieson, Nigel B. ; Johns, Amber L. ; Scarlett, Christopher J. ; Pajic, Marina ; Chou, Angela ; Pinese, Mark ; Humphris, Jeremy L. ; Jones, Marc D. ; Toon, Christopher ; Nagrial, Adnan M. ; Chantrill, Lorraine A. ; Chin, Venessa T. ; Pinho, Andreia V. ; Rooman, Ilse ; Cowley, Mark J. ; Wu, Jianmin ; Mead, R. Scott ; Colvin, Emily K. ; Samra, Jaswinder S. ; Corbo, Vincenzo ; Bassi, Claudio ; Falconi, Massimo ; Lawlor, Rita T. ; Crippa, Stefano ; Sperandio, Nicola ; Bersani, Samantha ; Dickson, Euan J. ; Mohamed, Mohamed A A ; Oien, Karin A. ; Foulis, Alan K. ; Musgrove, Elizabeth A. ; Sutherland, Robert L. ; Kench, James G. ; Carter, C. Ross ; Gill, Anthony J. ; Scarpa, Aldo ; McKay, Colin J. ; Biankin, Andrew V. / Histomolecular phenotypes and outcome in adenocarcinoma of the ampulla of vater. In: Journal of Clinical Oncology. 2013 ; Vol. 31, No. 10. pp. 1348-1356.
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abstract = "Purpose: Individuals with adenocarcinoma of the ampulla of Vater demonstrate a broad range of outcomes, presumably because these cancers may arise from any one of the three epithelia that converge at that location. This variability poses challenges for clinical decision making and the development of novel therapeutic strategies. Patients and Methods: We assessed the potential clinical utility of histomolecular phenotypes defined using a combination of histopathology and protein expression (CDX2 and MUC1) in 208 patients from three independent cohorts who underwent surgical resection for adenocarcinoma of the ampulla of Vater. Results: Histologic subtype and CDX2 and MUC1 expression were significant prognostic variables. Patients with a histomolecular pancreaticobiliary phenotype (CDX2 negative, MUC1 positive) segregated into a poor prognostic group in the training (hazard ratio [HR], 3.34; 95{\%} CI, 1.69 to 6.62; P < .001) and both validation cohorts (HR, 5.65; 95{\%} CI, 2.77 to 11.5; P < .001 and HR, 2.78; 95{\%} CI, 1.25 to 7.17; P = .0119) compared with histomolecular nonpancreaticobiliary carcinomas. Further stratification by lymph node (LN) status defined three clinically relevant subgroups: one, patients with histomolecular nonpancreaticobiliary (intestinal) carcinoma without LN metastases who had an excellent prognosis; two, those with histomolecular pancreaticobiliary carcinoma with LN metastases who had a poor outcome; and three, the remainder of patients (nonpancreaticobiliary, LN positive or pancreaticobiliary, LN negative) who had an intermediate outcome. Conclusion: Histopathologic and molecular criteria combine to define clinically relevant histomolecular phenotypes of adenocarcinoma of the ampulla of Vater and potentially represent distinct diseases with significant implications for current therapeutic strategies, the ability to interpret past clinical trials, and future trial design.",
author = "Chang, {David K.} and Jamieson, {Nigel B.} and Johns, {Amber L.} and Scarlett, {Christopher J.} and Marina Pajic and Angela Chou and Mark Pinese and Humphris, {Jeremy L.} and Jones, {Marc D.} and Christopher Toon and Nagrial, {Adnan M.} and Chantrill, {Lorraine A.} and Chin, {Venessa T.} and Pinho, {Andreia V.} and Ilse Rooman and Cowley, {Mark J.} and Jianmin Wu and Mead, {R. Scott} and Colvin, {Emily K.} and Samra, {Jaswinder S.} and Vincenzo Corbo and Claudio Bassi and Massimo Falconi and Lawlor, {Rita T.} and Stefano Crippa and Nicola Sperandio and Samantha Bersani and Dickson, {Euan J.} and Mohamed, {Mohamed A A} and Oien, {Karin A.} and Foulis, {Alan K.} and Musgrove, {Elizabeth A.} and Sutherland, {Robert L.} and Kench, {James G.} and Carter, {C. Ross} and Gill, {Anthony J.} and Aldo Scarpa and McKay, {Colin J.} and Biankin, {Andrew V.}",
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Chang, DK, Jamieson, NB, Johns, AL, Scarlett, CJ, Pajic, M, Chou, A, Pinese, M, Humphris, JL, Jones, MD, Toon, C, Nagrial, AM, Chantrill, LA, Chin, VT, Pinho, AV, Rooman, I, Cowley, MJ, Wu, J, Mead, RS, Colvin, EK, Samra, JS, Corbo, V, Bassi, C, Falconi, M, Lawlor, RT, Crippa, S, Sperandio, N, Bersani, S, Dickson, EJ, Mohamed, MAA, Oien, KA, Foulis, AK, Musgrove, EA, Sutherland, RL, Kench, JG, Carter, CR, Gill, AJ, Scarpa, A, McKay, CJ & Biankin, AV 2013, 'Histomolecular phenotypes and outcome in adenocarcinoma of the ampulla of vater', Journal of Clinical Oncology, vol. 31, no. 10, pp. 1348-1356. https://doi.org/10.1200/JCO.2012.46.8868

Histomolecular phenotypes and outcome in adenocarcinoma of the ampulla of vater. / Chang, David K.; Jamieson, Nigel B.; Johns, Amber L.; Scarlett, Christopher J.; Pajic, Marina; Chou, Angela; Pinese, Mark; Humphris, Jeremy L.; Jones, Marc D.; Toon, Christopher; Nagrial, Adnan M.; Chantrill, Lorraine A.; Chin, Venessa T.; Pinho, Andreia V.; Rooman, Ilse; Cowley, Mark J.; Wu, Jianmin; Mead, R. Scott; Colvin, Emily K.; Samra, Jaswinder S.; Corbo, Vincenzo; Bassi, Claudio; Falconi, Massimo; Lawlor, Rita T.; Crippa, Stefano; Sperandio, Nicola; Bersani, Samantha; Dickson, Euan J.; Mohamed, Mohamed A A; Oien, Karin A.; Foulis, Alan K.; Musgrove, Elizabeth A.; Sutherland, Robert L.; Kench, James G.; Carter, C. Ross; Gill, Anthony J.; Scarpa, Aldo; McKay, Colin J.; Biankin, Andrew V.

In: Journal of Clinical Oncology, Vol. 31, No. 10, 01.04.2013, p. 1348-1356.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Histomolecular phenotypes and outcome in adenocarcinoma of the ampulla of vater

AU - Chang, David K.

AU - Jamieson, Nigel B.

AU - Johns, Amber L.

AU - Scarlett, Christopher J.

AU - Pajic, Marina

AU - Chou, Angela

AU - Pinese, Mark

AU - Humphris, Jeremy L.

AU - Jones, Marc D.

AU - Toon, Christopher

AU - Nagrial, Adnan M.

AU - Chantrill, Lorraine A.

AU - Chin, Venessa T.

AU - Pinho, Andreia V.

AU - Rooman, Ilse

AU - Cowley, Mark J.

AU - Wu, Jianmin

AU - Mead, R. Scott

AU - Colvin, Emily K.

AU - Samra, Jaswinder S.

AU - Corbo, Vincenzo

AU - Bassi, Claudio

AU - Falconi, Massimo

AU - Lawlor, Rita T.

AU - Crippa, Stefano

AU - Sperandio, Nicola

AU - Bersani, Samantha

AU - Dickson, Euan J.

AU - Mohamed, Mohamed A A

AU - Oien, Karin A.

AU - Foulis, Alan K.

AU - Musgrove, Elizabeth A.

AU - Sutherland, Robert L.

AU - Kench, James G.

AU - Carter, C. Ross

AU - Gill, Anthony J.

AU - Scarpa, Aldo

AU - McKay, Colin J.

AU - Biankin, Andrew V.

PY - 2013/4/1

Y1 - 2013/4/1

N2 - Purpose: Individuals with adenocarcinoma of the ampulla of Vater demonstrate a broad range of outcomes, presumably because these cancers may arise from any one of the three epithelia that converge at that location. This variability poses challenges for clinical decision making and the development of novel therapeutic strategies. Patients and Methods: We assessed the potential clinical utility of histomolecular phenotypes defined using a combination of histopathology and protein expression (CDX2 and MUC1) in 208 patients from three independent cohorts who underwent surgical resection for adenocarcinoma of the ampulla of Vater. Results: Histologic subtype and CDX2 and MUC1 expression were significant prognostic variables. Patients with a histomolecular pancreaticobiliary phenotype (CDX2 negative, MUC1 positive) segregated into a poor prognostic group in the training (hazard ratio [HR], 3.34; 95% CI, 1.69 to 6.62; P < .001) and both validation cohorts (HR, 5.65; 95% CI, 2.77 to 11.5; P < .001 and HR, 2.78; 95% CI, 1.25 to 7.17; P = .0119) compared with histomolecular nonpancreaticobiliary carcinomas. Further stratification by lymph node (LN) status defined three clinically relevant subgroups: one, patients with histomolecular nonpancreaticobiliary (intestinal) carcinoma without LN metastases who had an excellent prognosis; two, those with histomolecular pancreaticobiliary carcinoma with LN metastases who had a poor outcome; and three, the remainder of patients (nonpancreaticobiliary, LN positive or pancreaticobiliary, LN negative) who had an intermediate outcome. Conclusion: Histopathologic and molecular criteria combine to define clinically relevant histomolecular phenotypes of adenocarcinoma of the ampulla of Vater and potentially represent distinct diseases with significant implications for current therapeutic strategies, the ability to interpret past clinical trials, and future trial design.

AB - Purpose: Individuals with adenocarcinoma of the ampulla of Vater demonstrate a broad range of outcomes, presumably because these cancers may arise from any one of the three epithelia that converge at that location. This variability poses challenges for clinical decision making and the development of novel therapeutic strategies. Patients and Methods: We assessed the potential clinical utility of histomolecular phenotypes defined using a combination of histopathology and protein expression (CDX2 and MUC1) in 208 patients from three independent cohorts who underwent surgical resection for adenocarcinoma of the ampulla of Vater. Results: Histologic subtype and CDX2 and MUC1 expression were significant prognostic variables. Patients with a histomolecular pancreaticobiliary phenotype (CDX2 negative, MUC1 positive) segregated into a poor prognostic group in the training (hazard ratio [HR], 3.34; 95% CI, 1.69 to 6.62; P < .001) and both validation cohorts (HR, 5.65; 95% CI, 2.77 to 11.5; P < .001 and HR, 2.78; 95% CI, 1.25 to 7.17; P = .0119) compared with histomolecular nonpancreaticobiliary carcinomas. Further stratification by lymph node (LN) status defined three clinically relevant subgroups: one, patients with histomolecular nonpancreaticobiliary (intestinal) carcinoma without LN metastases who had an excellent prognosis; two, those with histomolecular pancreaticobiliary carcinoma with LN metastases who had a poor outcome; and three, the remainder of patients (nonpancreaticobiliary, LN positive or pancreaticobiliary, LN negative) who had an intermediate outcome. Conclusion: Histopathologic and molecular criteria combine to define clinically relevant histomolecular phenotypes of adenocarcinoma of the ampulla of Vater and potentially represent distinct diseases with significant implications for current therapeutic strategies, the ability to interpret past clinical trials, and future trial design.

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U2 - 10.1200/JCO.2012.46.8868

DO - 10.1200/JCO.2012.46.8868

M3 - Article

VL - 31

SP - 1348

EP - 1356

JO - Journal of Clinical Oncology

T2 - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 1527-7755

IS - 10

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Chang DK, Jamieson NB, Johns AL, Scarlett CJ, Pajic M, Chou A et al. Histomolecular phenotypes and outcome in adenocarcinoma of the ampulla of vater. Journal of Clinical Oncology. 2013 Apr 1;31(10):1348-1356. https://doi.org/10.1200/JCO.2012.46.8868