Co-overexpression of p53 protein and epidermal growth factor receptor in human papillary thyroid carcinomas correlated with lymph node metastasis, tumor size and clinicopathologic stage.

Y Qiu MD 1, B Chen MD2, PhD, Y Ohtsuki MD,PhD,3 M Furihata MD, PhD,3 T Takeuchi MD, PhD,3J Iwata MD, PhD 3, S Liang MD, PhD,3 H Sonobe MD, PhD3

1Deptartment of Molecular Cardiology, Cleveland Clinic Foundation, Cleveland, OH 2Endocrine Research Unit, Mayo Clinic Foundation, Rochester, MN 3Department of Pathology, Kochi Medical School, Nankoku, Kochi, Japan

AIM: Examined the relationship between clinicopathologic features and the expressions of p53 protein or epidermal growth factor receptor (EGFR), and co-overexpressions of p53 protein and EGFR in papillary thyroid carcinomas (PTC), in an attempt to clarify the clinicopathologic significance. METHODS: 111 patients with PTC underwent pathologic examination between 1980-1997 in the Department of Pathology of Kochi Medical School. Three micro-meter tissue sections from formalin-fixed and paraffin-embedded tissues of PTC were stained using a monoclonal antibody to p53 protein and a rabbit polyclonal antibody to EGFR. Expressions were assessed by an immunohistochemical staining method (streptavidin-biotin-peroxidase complex method, Dako LSAB Kit, Kyoto, Japan) according to the kit manual. RESULTS: In PTC, positive staining for p53 in dewaxed sections was present in nuclei or cytoplasm, or in both, whereas surface linear or cytoplasmic staining for EGFR was observed with varying degrees of extent and intensity. Positive reaction (more than 10% of tumor cells positive) was observed in 65 cases (58. 5%) for p53, and in 87 cases (78.4%) for EGFR. A significant correlation was found between p53 protein and EGFR overexpressions (p<0.01). Notably, p53-positive cases always exhibited positive staining for EGFR. Forty-four patients (39.6%) exhibited concomitant lymphnode metastasis (LNM), most of whom had both p53 and EGFR expression in primary foci. Statistical analysis revealed that co-expression of p53 protein and EGFR was significantly correlated with LNM, tumor size and clinicopathologic stage, but no correlation was found between their co-overexpression and age or sex. CONCLUSIONS: Overexpression of p53 protein or EGFR in PTC tends to be associated with a high frequency of LNM, increased tumor size and advanced clinicopathologic stage, and that co-expression of both p53 protein and EGFR may predispose to growth and progression of PTC, and also may be clinicopathologic and prognostic indicators of PTC.

KEY WORDS: Keywords p53, epidermal growth factor receptor, papillary thyroid carcinoma, immunohistochemistry.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Metastasis.