Abstract
c-erbB-2 protein expression was investigated immunohistochemically in frozen thyroid tissue specimens from 42 patients using a polyclonal sheep antibody. c-erbB-2 immunoreactivity was detected in 12 out of 17 papillary carcinomas, while no c-erbB-2 protein immunostaining was seen in cases of follicular adenoma (five cases), follicular carcinoma (five cases) or medullary carcinoma (one case), nor in cases of non-neoplastic tissue, including normal thyroid tissue from tumour-bearing glands. RNA was extracted from 51 thyroid tissue samples from 34 of the above patients, and c-erbB-2 mRNA was analysed by slot-blot hybridisation. c-erbB-2 mRNA was detectable in all samples, but papillary carcinomas and lymph node metastases showed significantly higher levels of c-erbB-2 mRNA compared to non-neoplastic tissue. The present demonstration of positive c-erbB-2 immunostaining in papillary thyroid carcinomas is contradictory to previous findings on formalin-fixed, paraffin-embedded material, and emphasises the importance of tissue quality for c-erbB-2 protein detection.
Full text
PDF





Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aasland R., Akslen L. A., Varhaug J. E., Lillehaug J. R. Co-expression of the genes encoding transforming growth factor-alpha and its receptor in papillary carcinomas of the thyroid. Int J Cancer. 1990 Sep 15;46(3):382–387. doi: 10.1002/ijc.2910460308. [DOI] [PubMed] [Google Scholar]
- Aasland R., Lillehaug J. R., Male R., Jøsendal O., Varhaug J. E., Kleppe K. Expression of oncogenes in thyroid tumours: coexpression of c-erbB2/neu and c-erbB. Br J Cancer. 1988 Apr;57(4):358–363. doi: 10.1038/bjc.1988.82. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Akiyama T., Sudo C., Ogawara H., Toyoshima K., Yamamoto T. The product of the human c-erbB-2 gene: a 185-kilodalton glycoprotein with tyrosine kinase activity. Science. 1986 Jun 27;232(4758):1644–1646. doi: 10.1126/science.3012781. [DOI] [PubMed] [Google Scholar]
- Bongarzone I., Pierotti M. A., Monzini N., Mondellini P., Manenti G., Donghi R., Pilotti S., Grieco M., Santoro M., Fusco A. High frequency of activation of tyrosine kinase oncogenes in human papillary thyroid carcinoma. Oncogene. 1989 Dec;4(12):1457–1462. [PubMed] [Google Scholar]
- Coombs L. M., Pigott D. A., Sweeney E., Proctor A. J., Eydmann M. E., Parkinson C., Knowles M. A. Amplification and over-expression of c-erbB-2 in transitional cell carcinoma of the urinary bladder. Br J Cancer. 1991 Apr;63(4):601–608. doi: 10.1038/bjc.1991.139. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Corbett I. P., Henry J. A., Angus B., Watchorn C. J., Wilkinson L., Hennessy C., Gullick W. J., Tuzi N. L., May F. E., Westley B. R. NCL-CB11, a new monoclonal antibody recognizing the internal domain of the c-erbB-2 oncogene protein effective for use on formalin-fixed, paraffin-embedded tissue. J Pathol. 1990 May;161(1):15–25. doi: 10.1002/path.1711610105. [DOI] [PubMed] [Google Scholar]
- Coussens L., Yang-Feng T. L., Liao Y. C., Chen E., Gray A., McGrath J., Seeburg P. H., Libermann T. A., Schlessinger J., Francke U. Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene. Science. 1985 Dec 6;230(4730):1132–1139. doi: 10.1126/science.2999974. [DOI] [PubMed] [Google Scholar]
- De Potter C. R., Van Daele S., Van de Vijver M. J., Pauwels C., Maertens G., De Boever J., Vandekerckhove D., Roels H. The expression of the neu oncogene product in breast lesions and in normal fetal and adult human tissues. Histopathology. 1989 Oct;15(4):351–362. doi: 10.1111/j.1365-2559.1989.tb01587.x. [DOI] [PubMed] [Google Scholar]
- Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
- Fusco A., Grieco M., Santoro M., Berlingieri M. T., Pilotti S., Pierotti M. A., Della Porta G., Vecchio G. A new oncogene in human thyroid papillary carcinomas and their lymph-nodal metastases. Nature. 1987 Jul 9;328(6126):170–172. doi: 10.1038/328170a0. [DOI] [PubMed] [Google Scholar]
- Grieco M., Santoro M., Berlingieri M. T., Melillo R. M., Donghi R., Bongarzone I., Pierotti M. A., Della Porta G., Fusco A., Vecchio G. PTC is a novel rearranged form of the ret proto-oncogene and is frequently detected in vivo in human thyroid papillary carcinomas. Cell. 1990 Feb 23;60(4):557–563. doi: 10.1016/0092-8674(90)90659-3. [DOI] [PubMed] [Google Scholar]
- Gullick W. J., Love S. B., Wright C., Barnes D. M., Gusterson B., Harris A. L., Altman D. G. c-erbB-2 protein overexpression in breast cancer is a risk factor in patients with involved and uninvolved lymph nodes. Br J Cancer. 1991 Mar;63(3):434–438. doi: 10.1038/bjc.1991.100. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hall P. A., Hughes C. M., Staddon S. L., Richman P. I., Gullick W. J., Lemoine N. R. The c-erb B-2 proto-oncogene in human pancreatic cancer. J Pathol. 1990 Jul;161(3):195–200. doi: 10.1002/path.1711610305. [DOI] [PubMed] [Google Scholar]
- Jasani B., Wyllie F. S., Wright P. A., Lemoine N. R., Williams E. D., Wynford-Thomas D. Immunocytochemically detectable TGF-beta associated with malignancy in thyroid epithelial neoplasia. Growth Factors. 1990;2(2-3):149–155. doi: 10.3109/08977199009071501. [DOI] [PubMed] [Google Scholar]
- Lemoine N. R., Mayall E. S., Wyllie F. S., Williams E. D., Goyns M., Stringer B., Wynford-Thomas D. High frequency of ras oncogene activation in all stages of human thyroid tumorigenesis. Oncogene. 1989 Feb;4(2):159–164. [PubMed] [Google Scholar]
- Lemoine N. R., Staddon S., Dickson C., Barnes D. M., Gullick W. J. Absence of activating transmembrane mutations in the c-erbB-2 proto-oncogene in human breast cancer. Oncogene. 1990 Feb;5(2):237–239. [PubMed] [Google Scholar]
- Lemoine N. R., Wyllie F. S., Lillehaug J. R., Staddon S. L., Hughes C. M., Aasland R., Shaw J., Varhaug J. E., Brown C. L., Gullick W. J. Absence of abnormalities of the c-erbB-1 and c-erbB-2 proto-oncogenes in human thyroid neoplasia. Eur J Cancer. 1990;26(7):777–779. doi: 10.1016/0277-5379(90)90149-n. [DOI] [PubMed] [Google Scholar]
- Lovekin C., Ellis I. O., Locker A., Robertson J. F., Bell J., Nicholson R., Gullick W. J., Elston C. W., Blamey R. W. c-erbB-2 oncoprotein expression in primary and advanced breast cancer. Br J Cancer. 1991 Mar;63(3):439–443. doi: 10.1038/bjc.1991.101. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lupu R., Colomer R., Zugmaier G., Sarup J., Shepard M., Slamon D., Lippman M. E. Direct interaction of a ligand for the erbB2 oncogene product with the EGF receptor and p185erbB2. Science. 1990 Sep 28;249(4976):1552–1555. doi: 10.1126/science.2218496. [DOI] [PubMed] [Google Scholar]
- Natali P. G., Nicotra M. R., Bigotti A., Venturo I., Slamon D. J., Fendly B. M., Ullrich A. Expression of the p185 encoded by HER2 oncogene in normal and transformed human tissues. Int J Cancer. 1990 Mar 15;45(3):457–461. doi: 10.1002/ijc.2910450314. [DOI] [PubMed] [Google Scholar]
- O'Reilly S. M., Barnes D. M., Camplejohn R. S., Bartkova J., Gregory W. M., Richards M. A. The relationship between c-erbB-2 expression, S-phase fraction and prognosis in breast cancer. Br J Cancer. 1991 Mar;63(3):444–446. doi: 10.1038/bjc.1991.102. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Roncalli M., Springall D. R., Varndell I. M., Gaitonde V. V., Hamid Q., Ibrahim N. B., Grimelius L., Wilander E., Polak J. M., Coggi G. Oncoprotein immunoreactivity in human endocrine tumours. J Pathol. 1991 Feb;163(2):117–127. doi: 10.1002/path.1711630207. [DOI] [PubMed] [Google Scholar]
- Schechter A. L., Hung M. C., Vaidyanathan L., Weinberg R. A., Yang-Feng T. L., Francke U., Ullrich A., Coussens L. The neu gene: an erbB-homologous gene distinct from and unlinked to the gene encoding the EGF receptor. Science. 1985 Sep 6;229(4717):976–978. doi: 10.1126/science.2992090. [DOI] [PubMed] [Google Scholar]
- Slamon D. J., Clark G. M., Wong S. G., Levin W. J., Ullrich A., McGuire W. L. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987 Jan 9;235(4785):177–182. doi: 10.1126/science.3798106. [DOI] [PubMed] [Google Scholar]
- Slamon D. J., Godolphin W., Jones L. A., Holt J. A., Wong S. G., Keith D. E., Levin W. J., Stuart S. G., Udove J., Ullrich A. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 1989 May 12;244(4905):707–712. doi: 10.1126/science.2470152. [DOI] [PubMed] [Google Scholar]
- Suárez H. G., Du Villard J. A., Caillou B., Schlumberger M., Tubiana M., Parmentier C., Monier R. Detection of activated ras oncogenes in human thyroid carcinomas. Oncogene. 1988 Apr;2(4):403–406. [PubMed] [Google Scholar]
- Terrier P., Sheng Z. M., Schlumberger M., Tubiana M., Caillou B., Travagli J. P., Fragu P., Parmentier C., Riou G. Structure and expression of c-myc and c-fos proto-oncogenes in thyroid carcinomas. Br J Cancer. 1988 Jan;57(1):43–47. doi: 10.1038/bjc.1988.6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Venter D. J., Tuzi N. L., Kumar S., Gullick W. J. Overexpression of the c-erbB-2 oncoprotein in human breast carcinomas: immunohistological assessment correlates with gene amplification. Lancet. 1987 Jul 11;2(8550):69–72. doi: 10.1016/s0140-6736(87)92736-x. [DOI] [PubMed] [Google Scholar]
- Whitley G. S., Nussey S. S., Johnstone A. P. SGHTL-34, a thyrotrophin-responsive immortalised human thyroid cell line generated by transfection. Mol Cell Endocrinol. 1987 Aug;52(3):279–284. doi: 10.1016/0303-7207(87)90056-6. [DOI] [PubMed] [Google Scholar]
- Williams D. W., Williams E. D., Wynford-Thomas D. Loss of dependence on IGF-1 for proliferation of human thyroid adenoma cells. Br J Cancer. 1988 Jun;57(6):535–539. doi: 10.1038/bjc.1988.124. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Winstanley J., Cooke T., Murray G. D., Platt-Higgins A., George W. D., Holt S., Myskov M., Spedding A., Barraclough B. R., Rudland P. S. The long term prognostic significance of c-erbB-2 in primary breast cancer. Br J Cancer. 1991 Mar;63(3):447–450. doi: 10.1038/bjc.1991.103. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wright C., Mellon K., Neal D. E., Johnston P., Corbett I. P., Horne C. H. Expression of c-erbB-2 protein product in bladder cancer. Br J Cancer. 1990 Nov;62(5):764–765. doi: 10.1038/bjc.1990.375. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wyllie F. S., Lemoine N. R., Williams E. D., Wynford-Thomas D. Structure and expression of nuclear oncogenes in multi-stage thyroid tumorigenesis. Br J Cancer. 1989 Oct;60(4):561–565. doi: 10.1038/bjc.1989.313. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yamamoto T., Ikawa S., Akiyama T., Semba K., Nomura N., Miyajima N., Saito T., Toyoshima K. Similarity of protein encoded by the human c-erb-B-2 gene to epidermal growth factor receptor. Nature. 1986 Jan 16;319(6050):230–234. doi: 10.1038/319230a0. [DOI] [PubMed] [Google Scholar]
- van de Vijver M. J., Mooi W. J., Wisman P., Peterse J. L., Nusse R. Immunohistochemical detection of the neu protein in tissue sections of human breast tumors with amplified neu DNA. Oncogene. 1988 Feb;2(2):175–178. [PubMed] [Google Scholar]
- van de Vijver M., van de Bersselaar R., Devilee P., Cornelisse C., Peterse J., Nusse R. Amplification of the neu (c-erbB-2) oncogene in human mammmary tumors is relatively frequent and is often accompanied by amplification of the linked c-erbA oncogene. Mol Cell Biol. 1987 May;7(5):2019–2023. doi: 10.1128/mcb.7.5.2019. [DOI] [PMC free article] [PubMed] [Google Scholar]


