Expression and prognostic significance of 14-3-3σ and ERM family protein expression in periampullary neoplasms

Steven R. Hustinx, Noriyoshi Fukushima, Marianna L. Zahurak, Taylor Sohn Riall, Anirban Maitra, Lodewijk Brosens, John L. Cameron, Charles J. Yeo, G. Johan A Offerhaus, Ralph H. Hruban, Michael Goggins

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Aberrant gene expression in pancreatic ductal adenocarcinomas contributes to the dismal outcome of patients who develop this disease. The 5′ region of 14-3-3σ (stratifin) is hypomethylated in pancreatic adenocarcinomas and is associated with gene overexpression. In multiple experimental systems, ezrin (ERM, Radixin, Moesin) has been identified as being important in the metastatic behavior of pancreatic and other cancers. We investigated the prognostic significance of aberrant expression of 14-3-3σ and the ERM proteins (Ezrin, radixin, Moesin) in a series of invasive periampullary adenocarcinomas including 300 infiltrating pancreatic adenocarcinomas, 54 ampullary adenocarcinomas, and 33 noninvasive intraductal papillary mucinous neoplasms from patients who underwent pancreaticoduodenal resection at The Johns Hopkins Hospital, Baltimore, MD, between 1991 and 2003. Two-hundred fourty-four (82%) primary infiltrating adenocarcinomas of the pancreas demonstrated positive expression of the 14-3-3σ, 45 (15%) showed weak immunolabelling, and 9 (3%) were negative. 201 (68%) showed positive immunolabeling of the ERM proteins, 75 (25%) demonstrated weak expression and 20 (7%) no expression. A similar proportion of ampullary cancers showed 14-3-3σ and ERM protein expression. Expression of 14-3-3σ and ERM protein was more likely in poorly differentiated cancers (p = 0.00005), and their expression was associated with poor survival in univariate analysis (p = 0.09). By multivariate analysis, patients whose cancers expressed 14-3-3σ, but not ERM tended to have a poorer prognosis (Hazard ratio, 1.4; 0.9-2.2, p = 0.14). Aberrant expression of 14-3-3σ may contribute to the outcome of patients with pancreatic ductal adenocarcinoma.

Original languageEnglish (US)
Pages (from-to)596-601
Number of pages6
JournalCancer Biology and Therapy
Volume4
Issue number5
StatePublished - May 2005
Externally publishedYes

Fingerprint

Adenocarcinoma
14-3-3 Proteins
Neoplasms
Proteins
Baltimore
Pancreatic Neoplasms
Pancreas
Multivariate Analysis
Gene Expression
Survival
Genes
moesin
radixin
ezrin

Keywords

  • 14-3-3σ
  • Ampullary adenocarcinoma
  • DNA methylation
  • Ezrin
  • Intraductal papillary mucinous neoplasm
  • Pancreatic cancer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Hustinx, S. R., Fukushima, N., Zahurak, M. L., Riall, T. S., Maitra, A., Brosens, L., ... Goggins, M. (2005). Expression and prognostic significance of 14-3-3σ and ERM family protein expression in periampullary neoplasms. Cancer Biology and Therapy, 4(5), 596-601.

Expression and prognostic significance of 14-3-3σ and ERM family protein expression in periampullary neoplasms. / Hustinx, Steven R.; Fukushima, Noriyoshi; Zahurak, Marianna L.; Riall, Taylor Sohn; Maitra, Anirban; Brosens, Lodewijk; Cameron, John L.; Yeo, Charles J.; Offerhaus, G. Johan A; Hruban, Ralph H.; Goggins, Michael.

In: Cancer Biology and Therapy, Vol. 4, No. 5, 05.2005, p. 596-601.

Research output: Contribution to journalArticle

Hustinx, SR, Fukushima, N, Zahurak, ML, Riall, TS, Maitra, A, Brosens, L, Cameron, JL, Yeo, CJ, Offerhaus, GJA, Hruban, RH & Goggins, M 2005, 'Expression and prognostic significance of 14-3-3σ and ERM family protein expression in periampullary neoplasms', Cancer Biology and Therapy, vol. 4, no. 5, pp. 596-601.
Hustinx SR, Fukushima N, Zahurak ML, Riall TS, Maitra A, Brosens L et al. Expression and prognostic significance of 14-3-3σ and ERM family protein expression in periampullary neoplasms. Cancer Biology and Therapy. 2005 May;4(5):596-601.
Hustinx, Steven R. ; Fukushima, Noriyoshi ; Zahurak, Marianna L. ; Riall, Taylor Sohn ; Maitra, Anirban ; Brosens, Lodewijk ; Cameron, John L. ; Yeo, Charles J. ; Offerhaus, G. Johan A ; Hruban, Ralph H. ; Goggins, Michael. / Expression and prognostic significance of 14-3-3σ and ERM family protein expression in periampullary neoplasms. In: Cancer Biology and Therapy. 2005 ; Vol. 4, No. 5. pp. 596-601.
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abstract = "Aberrant gene expression in pancreatic ductal adenocarcinomas contributes to the dismal outcome of patients who develop this disease. The 5′ region of 14-3-3σ (stratifin) is hypomethylated in pancreatic adenocarcinomas and is associated with gene overexpression. In multiple experimental systems, ezrin (ERM, Radixin, Moesin) has been identified as being important in the metastatic behavior of pancreatic and other cancers. We investigated the prognostic significance of aberrant expression of 14-3-3σ and the ERM proteins (Ezrin, radixin, Moesin) in a series of invasive periampullary adenocarcinomas including 300 infiltrating pancreatic adenocarcinomas, 54 ampullary adenocarcinomas, and 33 noninvasive intraductal papillary mucinous neoplasms from patients who underwent pancreaticoduodenal resection at The Johns Hopkins Hospital, Baltimore, MD, between 1991 and 2003. Two-hundred fourty-four (82{\%}) primary infiltrating adenocarcinomas of the pancreas demonstrated positive expression of the 14-3-3σ, 45 (15{\%}) showed weak immunolabelling, and 9 (3{\%}) were negative. 201 (68{\%}) showed positive immunolabeling of the ERM proteins, 75 (25{\%}) demonstrated weak expression and 20 (7{\%}) no expression. A similar proportion of ampullary cancers showed 14-3-3σ and ERM protein expression. Expression of 14-3-3σ and ERM protein was more likely in poorly differentiated cancers (p = 0.00005), and their expression was associated with poor survival in univariate analysis (p = 0.09). By multivariate analysis, patients whose cancers expressed 14-3-3σ, but not ERM tended to have a poorer prognosis (Hazard ratio, 1.4; 0.9-2.2, p = 0.14). Aberrant expression of 14-3-3σ may contribute to the outcome of patients with pancreatic ductal adenocarcinoma.",
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