TY - JOUR
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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U2 - 10.1158/1078-0432.CCR-07-1543
DO - 10.1158/1078-0432.CCR-07-1543
M3 - Review article
C2 - 18316548
AN - SCOPUS:40949124676
SN - 1078-0432
VL - 14
SP - 1303
EP - 1309
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 5
ER -