High nuclear expression of phosphorylated extracellular signal-regulated kinase in tumor cells in colorectal glands is associated with poor outcome in colorectal cancer

Cheng Jeng Tai, Ching Hsiao Lee, Hung Chang Chen, Hsin Kai Wang, Ming Chung Jiang, Tzu Cheng Su, Ko Hung Shen, Shu Hui Lin, Chung Min Yeh, Chih Jung Chen, Kun Tu Yeh, Chun Chao Chang

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Extracellular signal-regulated kinase (ERK) is a major downstream transducer of Ras and plays an important role in transducing extracellular signals to the nuclei of cells. It is located in both the cytoplasm and the nucleus of cells. The nuclear localization of phosphorylated or activated ERK is involved in the invasive behavior of tumor cells. We studied the association between Ras mutation/ERK activation and the prognosis of patients with colorectal cancer. We analyzed 126 surgically resected colorectal cancer specimens for K-Ras mutation using direct sequencing. Activation/phosphorylation of ERK was assayed by immunohistochemistry with tissue microarray, and the staining intensity was analyzed using a semiquantitative scoring system. K-Ras mutations were detected in 32.5% (41/126) of the colorectal tumors. Colorectal glands are important functional organs in colorectal tissue and form the origin of colorectal carcinomas. Tissue microarray immunohistochemistry tests showed that tumors in colorectal cancer specimens were significantly stained for phospho-ERK (100%; 126/126), whereas nonneoplastic colorectal glands mainly showed faint phosphorylated ERK staining. High nuclear phospho-ERK expression in tumors was associated with highly invasive cancer stage and T status of the disease. Kaplan-Meier analysis showed that nuclear but not cytoplasmic phosphorylated ERK expression correlated with the patients' overall survival rate (P =.039). Colorectal adenomas including tubular adenomas and tubulovillous adenomas mainly showed weak cytoplasmic phospho-ERK expression. Our results suggest that immunohistologic analysis of phosphorylated ERK expression in colorectal glands may aid the diagnosis of colorectal cancer and that nuclear phosphorylated ERK might be a valuable prognostic marker for colorectal cancer.

Original languageEnglish
Pages (from-to)165-171
Number of pages7
JournalAnnals of Diagnostic Pathology
Volume17
Issue number2
DOIs
Publication statusPublished - Apr 2013

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Extracellular Signal-Regulated MAP Kinases
Colorectal Neoplasms
Neoplasms
Adenoma
Cell Nucleus
Mutation
Immunohistochemistry
Staining and Labeling
Kaplan-Meier Estimate
Transducers
Cytoplasm
Survival Rate
Phosphorylation

Keywords

  • Colorectal adenomas
  • Colorectal cancer
  • ERK
  • Nuclear
  • Phosphorylation
  • Ras

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

High nuclear expression of phosphorylated extracellular signal-regulated kinase in tumor cells in colorectal glands is associated with poor outcome in colorectal cancer. / Tai, Cheng Jeng; Lee, Ching Hsiao; Chen, Hung Chang; Wang, Hsin Kai; Jiang, Ming Chung; Su, Tzu Cheng; Shen, Ko Hung; Lin, Shu Hui; Yeh, Chung Min; Chen, Chih Jung; Yeh, Kun Tu; Chang, Chun Chao.

In: Annals of Diagnostic Pathology, Vol. 17, No. 2, 04.2013, p. 165-171.

Research output: Contribution to journalArticle

Tai, Cheng Jeng ; Lee, Ching Hsiao ; Chen, Hung Chang ; Wang, Hsin Kai ; Jiang, Ming Chung ; Su, Tzu Cheng ; Shen, Ko Hung ; Lin, Shu Hui ; Yeh, Chung Min ; Chen, Chih Jung ; Yeh, Kun Tu ; Chang, Chun Chao. / High nuclear expression of phosphorylated extracellular signal-regulated kinase in tumor cells in colorectal glands is associated with poor outcome in colorectal cancer. In: Annals of Diagnostic Pathology. 2013 ; Vol. 17, No. 2. pp. 165-171.
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AU - Tai, Cheng Jeng

AU - Lee, Ching Hsiao

AU - Chen, Hung Chang

AU - Wang, Hsin Kai

AU - Jiang, Ming Chung

AU - Su, Tzu Cheng

AU - Shen, Ko Hung

AU - Lin, Shu Hui

AU - Yeh, Chung Min

AU - Chen, Chih Jung

AU - Yeh, Kun Tu

AU - Chang, Chun Chao

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AB - Extracellular signal-regulated kinase (ERK) is a major downstream transducer of Ras and plays an important role in transducing extracellular signals to the nuclei of cells. It is located in both the cytoplasm and the nucleus of cells. The nuclear localization of phosphorylated or activated ERK is involved in the invasive behavior of tumor cells. We studied the association between Ras mutation/ERK activation and the prognosis of patients with colorectal cancer. We analyzed 126 surgically resected colorectal cancer specimens for K-Ras mutation using direct sequencing. Activation/phosphorylation of ERK was assayed by immunohistochemistry with tissue microarray, and the staining intensity was analyzed using a semiquantitative scoring system. K-Ras mutations were detected in 32.5% (41/126) of the colorectal tumors. Colorectal glands are important functional organs in colorectal tissue and form the origin of colorectal carcinomas. Tissue microarray immunohistochemistry tests showed that tumors in colorectal cancer specimens were significantly stained for phospho-ERK (100%; 126/126), whereas nonneoplastic colorectal glands mainly showed faint phosphorylated ERK staining. High nuclear phospho-ERK expression in tumors was associated with highly invasive cancer stage and T status of the disease. Kaplan-Meier analysis showed that nuclear but not cytoplasmic phosphorylated ERK expression correlated with the patients' overall survival rate (P =.039). Colorectal adenomas including tubular adenomas and tubulovillous adenomas mainly showed weak cytoplasmic phospho-ERK expression. Our results suggest that immunohistologic analysis of phosphorylated ERK expression in colorectal glands may aid the diagnosis of colorectal cancer and that nuclear phosphorylated ERK might be a valuable prognostic marker for colorectal cancer.

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