Immunohistochemical analysis of phosphotyrosine signal transducer and activator of transcription 3 and epidermal growth factor receptor autocrine signaling pathways in head and neck cancers and metastatic lymph nodes

Raja R. Seethala, William E. Gooding, Phoebe N. Handler, Bobby Collins, Qing Zhang, Jill M. Siegfried, Jennifer R. Grandis

Research output: Contribution to journalReview article

37 Citations (Scopus)

Abstract

Purpose: To determine the effect of tyrosine-phosphorylated signal transducer and activator of transcription 3 (pSTAT3) immunoexpression on survival in two independent cohorts of patients with squamous cell carcinoma of the head and neck (SCCHN) and to evaluate pSTAT3, transforming growth factor-α (TGF-α), epidermal growth factor receptor (EGFR), and gastrin-releasing peptide receptor (GRPR) expression in matched tumor and lymph node metastases in one of these cohorts. Experimental Technique: Immunostaining for pSTAT3, TGF-α, EGFR, and GRPR was done in two SCCHN cohorts (cohort 1, 61 tumors; cohort 2, 69 paired primary tumors and lymph node metastases). Semiquantitative scores derived from the product of staining intensity (scale 0-3) score and percentage of positive tumor cells were correlated with clinical outcome. Results: Immunoexpression of pSTAT3 did not correlate with clinical outcome in either cohort (cohort 1, P = 0.914; cohort 2, P = 0.312). In cohort 2, TGF-α and EGFR expression in the primary tumors showed some association with decreased disease-free survival (P = 0.0306 and P = 0.0985, respectively). Both pSTAT3 and EGFR showed a correlation of expression between tumor and matched lymph node metastasis (P < 0.0001 and P = 0.0046, respectively). In addition, the expression of EGFR and GRPR in the primary tumors correlated with TGF-α expression in paired nodal metastases (P = 0.0043 and P = 0.0268, respectively). In the nodal metastases, TGF-α expression correlated with EGFR expression (P = 0.0069). In primary tumors, GRPR expression correlated with TGF-α and EGFR expression (P = 0.0378 and P = 0.0026, respectively). Conclusions: These findings support an autocrine signaling pathway involving TGF-α, EGFR, and pSTAT3 in metastatic SCCHN as well as transactivation of EGFR by GRPR via TGF-α, but fails to identify an independent prognostic role for pSTAT3 immunoexpression.

Original languageEnglish (US)
Pages (from-to)1303-1309
Number of pages7
JournalClinical Cancer Research
Volume14
Issue number5
DOIs
StatePublished - Mar 1 2008
Externally publishedYes

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Autocrine Communication
STAT3 Transcription Factor
Phosphotyrosine
Head and Neck Neoplasms
Epidermal Growth Factor Receptor
Transforming Growth Factors
Bombesin Receptors
Lymph Nodes
Neoplasm Metastasis
Neoplasms
Transcriptional Activation
Disease-Free Survival
Tyrosine
Staining and Labeling

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Immunohistochemical analysis of phosphotyrosine signal transducer and activator of transcription 3 and epidermal growth factor receptor autocrine signaling pathways in head and neck cancers and metastatic lymph nodes. / Seethala, Raja R.; Gooding, William E.; Handler, Phoebe N.; Collins, Bobby; Zhang, Qing; Siegfried, Jill M.; Grandis, Jennifer R.

In: Clinical Cancer Research, Vol. 14, No. 5, 01.03.2008, p. 1303-1309.

Research output: Contribution to journalReview article

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title = "Immunohistochemical analysis of phosphotyrosine signal transducer and activator of transcription 3 and epidermal growth factor receptor autocrine signaling pathways in head and neck cancers and metastatic lymph nodes",
abstract = "Purpose: To determine the effect of tyrosine-phosphorylated signal transducer and activator of transcription 3 (pSTAT3) immunoexpression on survival in two independent cohorts of patients with squamous cell carcinoma of the head and neck (SCCHN) and to evaluate pSTAT3, transforming growth factor-α (TGF-α), epidermal growth factor receptor (EGFR), and gastrin-releasing peptide receptor (GRPR) expression in matched tumor and lymph node metastases in one of these cohorts. Experimental Technique: Immunostaining for pSTAT3, TGF-α, EGFR, and GRPR was done in two SCCHN cohorts (cohort 1, 61 tumors; cohort 2, 69 paired primary tumors and lymph node metastases). Semiquantitative scores derived from the product of staining intensity (scale 0-3) score and percentage of positive tumor cells were correlated with clinical outcome. Results: Immunoexpression of pSTAT3 did not correlate with clinical outcome in either cohort (cohort 1, P = 0.914; cohort 2, P = 0.312). In cohort 2, TGF-α and EGFR expression in the primary tumors showed some association with decreased disease-free survival (P = 0.0306 and P = 0.0985, respectively). Both pSTAT3 and EGFR showed a correlation of expression between tumor and matched lymph node metastasis (P < 0.0001 and P = 0.0046, respectively). In addition, the expression of EGFR and GRPR in the primary tumors correlated with TGF-α expression in paired nodal metastases (P = 0.0043 and P = 0.0268, respectively). In the nodal metastases, TGF-α expression correlated with EGFR expression (P = 0.0069). In primary tumors, GRPR expression correlated with TGF-α and EGFR expression (P = 0.0378 and P = 0.0026, respectively). Conclusions: These findings support an autocrine signaling pathway involving TGF-α, EGFR, and pSTAT3 in metastatic SCCHN as well as transactivation of EGFR by GRPR via TGF-α, but fails to identify an independent prognostic role for pSTAT3 immunoexpression.",
author = "Seethala, {Raja R.} and Gooding, {William E.} and Handler, {Phoebe N.} and Bobby Collins and Qing Zhang and Siegfried, {Jill M.} and Grandis, {Jennifer R.}",
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T1 - Immunohistochemical analysis of phosphotyrosine signal transducer and activator of transcription 3 and epidermal growth factor receptor autocrine signaling pathways in head and neck cancers and metastatic lymph nodes

AU - Seethala, Raja R.

AU - Gooding, William E.

AU - Handler, Phoebe N.

AU - Collins, Bobby

AU - Zhang, Qing

AU - Siegfried, Jill M.

AU - Grandis, Jennifer R.

PY - 2008/3/1

Y1 - 2008/3/1

N2 - Purpose: To determine the effect of tyrosine-phosphorylated signal transducer and activator of transcription 3 (pSTAT3) immunoexpression on survival in two independent cohorts of patients with squamous cell carcinoma of the head and neck (SCCHN) and to evaluate pSTAT3, transforming growth factor-α (TGF-α), epidermal growth factor receptor (EGFR), and gastrin-releasing peptide receptor (GRPR) expression in matched tumor and lymph node metastases in one of these cohorts. Experimental Technique: Immunostaining for pSTAT3, TGF-α, EGFR, and GRPR was done in two SCCHN cohorts (cohort 1, 61 tumors; cohort 2, 69 paired primary tumors and lymph node metastases). Semiquantitative scores derived from the product of staining intensity (scale 0-3) score and percentage of positive tumor cells were correlated with clinical outcome. Results: Immunoexpression of pSTAT3 did not correlate with clinical outcome in either cohort (cohort 1, P = 0.914; cohort 2, P = 0.312). In cohort 2, TGF-α and EGFR expression in the primary tumors showed some association with decreased disease-free survival (P = 0.0306 and P = 0.0985, respectively). Both pSTAT3 and EGFR showed a correlation of expression between tumor and matched lymph node metastasis (P < 0.0001 and P = 0.0046, respectively). In addition, the expression of EGFR and GRPR in the primary tumors correlated with TGF-α expression in paired nodal metastases (P = 0.0043 and P = 0.0268, respectively). In the nodal metastases, TGF-α expression correlated with EGFR expression (P = 0.0069). In primary tumors, GRPR expression correlated with TGF-α and EGFR expression (P = 0.0378 and P = 0.0026, respectively). Conclusions: These findings support an autocrine signaling pathway involving TGF-α, EGFR, and pSTAT3 in metastatic SCCHN as well as transactivation of EGFR by GRPR via TGF-α, but fails to identify an independent prognostic role for pSTAT3 immunoexpression.

AB - Purpose: To determine the effect of tyrosine-phosphorylated signal transducer and activator of transcription 3 (pSTAT3) immunoexpression on survival in two independent cohorts of patients with squamous cell carcinoma of the head and neck (SCCHN) and to evaluate pSTAT3, transforming growth factor-α (TGF-α), epidermal growth factor receptor (EGFR), and gastrin-releasing peptide receptor (GRPR) expression in matched tumor and lymph node metastases in one of these cohorts. Experimental Technique: Immunostaining for pSTAT3, TGF-α, EGFR, and GRPR was done in two SCCHN cohorts (cohort 1, 61 tumors; cohort 2, 69 paired primary tumors and lymph node metastases). Semiquantitative scores derived from the product of staining intensity (scale 0-3) score and percentage of positive tumor cells were correlated with clinical outcome. Results: Immunoexpression of pSTAT3 did not correlate with clinical outcome in either cohort (cohort 1, P = 0.914; cohort 2, P = 0.312). In cohort 2, TGF-α and EGFR expression in the primary tumors showed some association with decreased disease-free survival (P = 0.0306 and P = 0.0985, respectively). Both pSTAT3 and EGFR showed a correlation of expression between tumor and matched lymph node metastasis (P < 0.0001 and P = 0.0046, respectively). In addition, the expression of EGFR and GRPR in the primary tumors correlated with TGF-α expression in paired nodal metastases (P = 0.0043 and P = 0.0268, respectively). In the nodal metastases, TGF-α expression correlated with EGFR expression (P = 0.0069). In primary tumors, GRPR expression correlated with TGF-α and EGFR expression (P = 0.0378 and P = 0.0026, respectively). Conclusions: These findings support an autocrine signaling pathway involving TGF-α, EGFR, and pSTAT3 in metastatic SCCHN as well as transactivation of EGFR by GRPR via TGF-α, but fails to identify an independent prognostic role for pSTAT3 immunoexpression.

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