Immunohistochemical demonstration of ras p21 oncogene product in normal, benign, and malignant human thyroid tissues

Abstract

The p21 protein product of the cellular oncogene ras, designated ras p21, has been detected immunohistochemically in normal, benign and malignant human thyroid tissues. With the monoclonal antibody RAP-5 generated against a synthetic peptide corresponding to amino acid positions 10 to 17 of the ras p21 protein and an avidin-biotin-peroxidase complex (ABC), the expression of the ras p21 was evaluated in paraffin-embedded sections. Western blot analysis using fresh thyroid carcinoma tissue revealed double protein bands, one band was at molecular weight 21,000 and the other was a more rapidly migrating band at the molecular weight 17,500. Immunohistochemically, papillary adenocarcinomas of the thyroid showed moderate to intense stainings for ras p21 in most cases. Cytoplasmic and apical surface stainings were the most common patterns of immunoreactivity. Adenomas showed variable ras p21 positivity in cytoplasm and apical surface stainings of adenomas were negative to borderline in most cases. The cytoplasm of tissues of Hashimoto's thyroiditis, Graves' disease, and normal thyroid tissues was uniformly ras p21 positive, but the apical cell surface was nonreactive for ras p21 in all tissues. Judging from the findings obtained on this large series of normal, benign, and malignant thyroid tissues, the elevation of ras p21 may be a common event in thyroid neoplasm, and especially elevated ras expression in the apical cell surface may be characteristic to papillary carcinomas of the thyroid. This suggests that apical surface expression of ras p21 may be important in the development of thyroid carcinomas and be useful in differentiation of papillary adenocarcinoma.

A Radiation-Induced Gene Signature Distinguishes Post-Chernobyl from Sporadic Papillary Thyroid Cancers

“…2). An elevation of HRAS in the apical cell surface using immunohistochemistry was found especially in malignant thyroid tissues (31), which is in line with our findings. However, changes at the protein level are not necessarily reflected at the gene expression level, as shown after radiation exposure in cells of a murine cell line (32).…”

Expression of transforming growth factor α, amphiregulin and cripto-1 in human breast carcinomas

“…AR expression in the breast carcinomas was then evaluated since a specific 1.4 kb mRNA transcript for this growth factor has recently been shown to be expressed in several normal human mammary epithelial cell strains and in several human breast cancer cell lines (Plowman et (Table II). A variable number of tumours were present within (Bartek et al, 1990;Osborne et al, 1991;Mazars et al, 1992 (Aaronson, 1991;Sporn & Roberts, 1992 (Mizukami et al, 1990;Umekita et al, 1992). This difference in the frequency of TGF-a protein expression might be due to the use of monoclonal anti-TGFa antibodies in these studies as compared with the utilisation of a polyclonal anti-TGF-.a antibody in the present study.…”

Tumour necrosis factor- α and transforming growth factor- β are significantly associated with better prognosis in non-small cell lung carcinoma: putative relation with BCL-2-mediated neovascularization

“…TGF-β activity is generally inhibitory to epithelial cells in vitro and has several effects on the regulation of extracellular matrix components (Sporn et al, 1986). Moreover, the cellular response to TGF-β and the presence of several isoforms could be important factors for explaining the conflicting results regarding its activity (Mizukami et al, 1990;McCune et al, 1992;Walker et al, 1992).…”