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-alpha (TGF-alpha), 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-alpha, 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-alpha 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-alpha expression in paired nodal metastases (P = 0.0043 and P = 0.0268, respectively). In the nodal metastases, TGF-alpha expression correlated with EGFR expression (P = 0.0069). In primary tumors, GRPR expression correlated with TGF-alpha and EGFR expression (P = 0.0378 and P = 0.0026, respectively).

CONCLUSIONS:

These findings support an autocrine signaling pathway involving TGF-alpha, EGFR, and pSTAT3 in metastatic SCCHN as well as transactivation of EGFR by GRPR via TGF-alpha, but fails to identify an independent prognostic role for pSTAT3 immunoexpression.

• Authors: Raja R Seethala, William E Gooding, Phoebe N Handler, Bobby Collins, Qing Zhang, Jill M Siegfried, Jennifer R Grandis
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 14 Issue 5 Pg. 1303-9 (Mar 01 2008) ISSN: 1078-0432 [Print] United States
• PMID: 18316548 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Receptors, Bombesin
• STAT3 Transcription Factor
• STAT3 protein, human
• Transforming Growth Factor alpha
• Phosphotyrosine
• ErbB Receptors

Topics

• Adult
• Aged
• Aged, 80 and over
• Carcinoma, Squamous Cell (metabolism, secondary, therapy)
• Cohort Studies
• ErbB Receptors (genetics, metabolism)
• Female
• Head and Neck Neoplasms (metabolism, pathology, therapy)
• Humans
• Immunoenzyme Techniques
• Lymph Nodes (pathology)
• Lymphatic Metastasis
• Male
• Middle Aged
• Phosphotyrosine (metabolism)
• Receptors, Bombesin (metabolism)
• STAT3 Transcription Factor (metabolism)
• Signal Transduction
• Transcriptional Activation
• Transforming Growth Factor alpha (metabolism)