Oncoproteins and tumor progression in papillary thyroid carcinoma: presence of epidermal growth factor receptor, c-erbB-2 protein, estrogen receptor related protein, p21-ras protein, and proliferation indicators in relation to tumor recurrences and patien

Abstract:

BACKGROUND:The prognostic relevance of activated oncogenes and oncoproteins has not been well studied in papillary thyroid cancer, which is slow-growing, with only regional spread in most cases. Therefore, the influence of some protein markers and tumor cell proliferation on disease progress in a series of patients with surgically treated papillary thyroid carcinoma was studied. METHODS:One hundred twenty-seven patients with papillary thyroid carcinoma larger than 10 mm in greatest dimension were studied retrospectively, and the majority were treated with total or near-total thyroidectomy. Immunohistochemical and flow cytometric analyses of paraffin embedded tumor material were performed and the results were related to time to recurrence and thyroid cancer deaths using the univariate product-limit survival analysis and the multivariate Cox' regression method. RESULTS:Immunohistochemical expression of c-erbB-2 protein, estrogen receptor-related protein (p29), which may be regarded as an indicator of hormone-dependent growth, S-phase, G2M-phase, sex, age, histologic grade, and primary tumor extent were all of significant prognostic importance in univariate analyses of patient survival. In the final Cox' model, however, only male sex (P = 0.017), older age, (P < 0.00005) and high grade histologic features (P = 0.006) were associated independently with decreased survival. Among females, decreased expression of c-erbB-2 protein was independently related to decreased patient survival (P = 0.019). In multivariate analysis of time to recurrence, lymph node status (P = 0.0001), epidermal growth factor (EGF) receptor expression (P = 0.013) and estrogen receptor-related protein (P = 0.007) were independent risk indicators, and S-phase fraction (P = 0.074) showed a borderline significance. CONCLUSION:In this study, sex, age, and histologic grade were independent indicators of deaths from thyroid cancer. Lymph node metastases, EGF-receptor expression, and decreased estrogen receptor-related protein staining persisted as prognostic variables in the final multivariate analysis of recurrence free survival. Alterations in these oncogenes thus seem to play some role in disease progression in papillary thyroid carcinoma, although conventional variables are still important as prognostic indicators.

journal_name

Cancer

journal_title

Cancer

authors

Akslen LA,Varhaug JE

doi

10.1002/1097-0142(19951101)76:9<1643::aid-cncr2820

subject

Has Abstract

pub_date

1995-11-01 00:00:00

pages

1643-54

issue

9

eissn

0008-543X

issn

1097-0142

journal_volume

76

pub_type

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