Oncotarget

Research Papers:

Combination immunohistochemistry for SMAD4 and Runt-related transcription factor 3 may identify a favorable prognostic subgroup of pancreatic ductal adenocarcinomas

Yangkyu Lee, Hyejung Lee, Hyunjin Park, Jin-Won Kim, Jin-Hyeok Hwang, Jaihwan Kim, Yoo-Seok Yoon, Ho-Seong Han and Haeryoung Kim _

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Oncotarget. 2017; 8:76699-76711. https://doi.org/10.18632/oncotarget.20815

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Abstract

Yangkyu Lee1, Hyejung Lee2, Hyunjin Park2, Jin-Won Kim3, Jin-Hyeok Hwang3, Jaihwan Kim3, Yoo-Seok Yoon4, Ho-Seong Han4 and Haeryoung Kim2

1Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea

2Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea

3Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea

4Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea

Correspondence to:

Haeryoung Kim, email: [email protected]

Keywords: pancreatic ductal adenocarcinoma, SMAD4, RUNX3, immunohistochemistry, prognosis

Received: June 05, 2017     Accepted: August 23, 2017     Published: September 11, 2017

ABSTRACT

Purposes: SMAD4/DPC4 mutations have been associated with aggressive behavior in pancreatic ductal adenocarcinomas (PDAC), and it has recently been suggested that RUNX3 expression combined with SMAD4 status may predict the metastatic potential of PDACs. We evaluated the prognostic utility of SMAD4/RUNX3 status in human PDACs by immunohistochemistry.

Materials and Methods: Immunohistochemical stains were performed for SMAD4 and RUNX3 on 210 surgically resected PDACs, and the results were correlated with the clinicopathological features.

Results: Loss of SMAD4 expression was associated with poor overall survival (OS) (p = 0.015) and progression-free survival (PFS) (p = 0.044). Nuclear RUNX3 expression was associated with decreased OS (p = 0.010) and PFS (p = 0.009), and more frequent in poorly differentiated PDACs (p = 0.037). On combining RUNX3/SMAD4 status, RUNX3-/SMAD4+ PDACs demonstrated longer OS (p = 0.008, median time; RUNX3-/SMAD4+ 34 months, others 17 months) and PFS (p = 0.009, median time; RUNX3-/SMAD4+ 29 months, others 8 months) compared to RUNX3+/SMAD4+ and SMAD4- groups; RUNX3-/SMAD4+ was a significant independent predictive factor for both OS [p = 0.025, HR 1.842 (95% CI 1.079-3.143)] and PFS [p = 0.020, HR 1.850 (95% CI 1.100-3.113)].

Conclusions: SMAD4-positivity with RUNX3-negativity was a significant independent predictive factor for favorable OS and PFS in PDAC. This is the first and large clinicopathological study of RUNX3/SMAD4 expression status in human PDAC. Combination immunohistochemistry for SMAD4 and RUNX3 may help identify a favorable prognostic subgroup of PDAC.


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