Prognostic Impact of Phosphorylated Discoidin Domain Receptor-1 in Esophageal Cancer

Kiichi Sugimoto, Tomoaki Ito, Juhyung Woo, Ellen Tully, Koichi Sato, Hajime Orita, Malcolm V Brock, Edward Gabrielson

Research output: Contribution to journalArticle

Abstract

Background: Esophageal squamous cell carcinoma (ESCC) is common in East Asia and also is often deadly. We sought to determine whether measuring the discoidin domain receptor-1 (DDR1)—both total and phosphorylated proteins—could improve our ability to predict recurrence in ESCC. Materials and Methods: Total DDR1 and phosphorylated DDR1 (pDDR1) were measured using semiquantitative immunohistochemistry in a cohort of 60 patients with ESCC. Association between these immunohistochemical measurements and standard clinical-pathological variables such as patient recurrence-free survival was examined using univariate and multivariate analyses. Results: Six patients (10.0%) had regional recurrence and eight patients (13.3%) had distant recurrence. In univariate analysis, early disease recurrence correlated with intense staining of total DDR1 (P = 0.03) as well as intense staining of pDDR1 (P < 0.001). On multivariate analysis, only regional lymph node metastasis (P = 0.04, HR = 4.20) and intensity of pDDR1 immunohistochemistry (P = 0.03, HR = 4.27) emerged as significant independent prognostic factors for recurrence. Conclusions: This study suggests that immunohistochemical measurements of both the DDR1 protein and pDDR1 can provide prognostic value in ESCC, even when other clinical and pathological factors are also being considered.

Original languageEnglish (US)
Pages (from-to)479-486
Number of pages8
JournalJournal of Surgical Research
Volume235
DOIs
StatePublished - Mar 1 2019

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Esophageal Neoplasms
Recurrence
Multivariate Analysis
Immunohistochemistry
Staining and Labeling
Far East
Discoidin Domain Receptor 1
Lymph Nodes
Neoplasm Metastasis
Survival
Esophageal Squamous Cell Carcinoma

Keywords

  • Discoid domain receptor-1
  • Esophageal squamous cell carcinoma
  • Phosphorylation
  • Prognosis
  • Receptor tyrosine kinase

ASJC Scopus subject areas

  • Surgery

Cite this

Prognostic Impact of Phosphorylated Discoidin Domain Receptor-1 in Esophageal Cancer. / Sugimoto, Kiichi; Ito, Tomoaki; Woo, Juhyung; Tully, Ellen; Sato, Koichi; Orita, Hajime; Brock, Malcolm V; Gabrielson, Edward.

In: Journal of Surgical Research, Vol. 235, 01.03.2019, p. 479-486.

Research output: Contribution to journalArticle

Sugimoto, Kiichi ; Ito, Tomoaki ; Woo, Juhyung ; Tully, Ellen ; Sato, Koichi ; Orita, Hajime ; Brock, Malcolm V ; Gabrielson, Edward. / Prognostic Impact of Phosphorylated Discoidin Domain Receptor-1 in Esophageal Cancer. In: Journal of Surgical Research. 2019 ; Vol. 235. pp. 479-486.
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AU - Sato, Koichi

AU - Orita, Hajime

AU - Brock, Malcolm V

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N2 - Background: Esophageal squamous cell carcinoma (ESCC) is common in East Asia and also is often deadly. We sought to determine whether measuring the discoidin domain receptor-1 (DDR1)—both total and phosphorylated proteins—could improve our ability to predict recurrence in ESCC. Materials and Methods: Total DDR1 and phosphorylated DDR1 (pDDR1) were measured using semiquantitative immunohistochemistry in a cohort of 60 patients with ESCC. Association between these immunohistochemical measurements and standard clinical-pathological variables such as patient recurrence-free survival was examined using univariate and multivariate analyses. Results: Six patients (10.0%) had regional recurrence and eight patients (13.3%) had distant recurrence. In univariate analysis, early disease recurrence correlated with intense staining of total DDR1 (P = 0.03) as well as intense staining of pDDR1 (P < 0.001). On multivariate analysis, only regional lymph node metastasis (P = 0.04, HR = 4.20) and intensity of pDDR1 immunohistochemistry (P = 0.03, HR = 4.27) emerged as significant independent prognostic factors for recurrence. Conclusions: This study suggests that immunohistochemical measurements of both the DDR1 protein and pDDR1 can provide prognostic value in ESCC, even when other clinical and pathological factors are also being considered.

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