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Cytoplasmic staining of erb B‐2 but not mRNA levels correlates with differentiation in human thyroid neoplasia
Author(s) -
Sugg Sonia L.,
Ezzat Shereen,
Zheng Lei,
Rosen Irving B.,
Freeman Jeremy L.,
Asa Sylvia L.
Publication year - 1998
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1046/j.1365-2265.1998.00580.x
Subject(s) - immunohistochemistry , biology , messenger rna , thyroid carcinoma , pathology , thyroid , oncogene , microbiology and biotechnology , pax8 , gene , cancer research , endocrinology , medicine , cell cycle , transcription factor , genetics , immunology
OBJECTIVE Amplification and overexpression of the erb B‐2 proto‐oncogene in human carcinomas may have prognostic significance. Its role in thyroid carcinoma is controversial. We investigated human thyroid tumours for erb B‐2 gene amplification, activating mutations in the transmembrane domain, quantitative mRNA expression and protein expression. MATERIALS AND METHODS DNA and mRNA were extracted from 47 morphologically characterized, frozen thyroid tumours including 10 nodular hyperplasias, 3 follicular carcinomas and 34 papillary carcinomas (4 with tall‐cell features, 2 with insular and 2 with anaplastic de‐differentiation). DNA amplification was analysed by differential PCR. The transmembrane domain of erb B‐2 was sequenced in all tumours for activating mutations in position 659. Levels of mRNA expression were determined by competitive mRNA RT–PCR. Immunohistochemistry (IHC) for erb B‐2 protein expression in corresponding paraffin‐embedded samples was evaluated. RESULTS Our results showed no DNA amplification of erb B‐2. Sequencing of the transmembrane domain of erb B‐2 revealed no activating mutations. The level of mRNA expression was variable, 11 papillary carcinomas showing statistically significant elevated mRNA levels compared with corresponding normal thyroid tissue; however, this did not correlate with other indicators of poor prognosis. In contrast to elevated mRNA levels in tumours, the level of protein staining correlated with degree of differentiation, normal and hyperplastic tissue being strongly positive and poorly differentiated tumours negative. CONCLUSION There are no mutations or amplifications of the erb B‐2 gene in human thyroid tumours. Elevated erb B‐2 mRNA expression in some thyroid tumours is not associated with clinical features of poor prognosis; however, the significance of the elevated mRNA levels is unclear, as it did not result in protein overexpression. Instead, cytoplasmic erb B‐2 protein detection by IHC correlates with differentiation of human thyroid tumours and may be a feature of good prognosis.