Abstract
A series of 198 female breast cancer biopsies were analysed immunohistochemically for the expression of epidermal growth factor (EGF), with special emphasis on its prognostic significance. A total of 67/198 tumours (33.8%) were EGF-positive, 24 (12%) of which showed strong expression of EGF. EGF was usually expressed in the cytoplasm of the cancer cells but, in 22 cases, the normal ducts adjacent to the cancer showed positive staining as well. Strong EGF expression was related to distant metastases at diagnosis (P=0.04). Oestrogen(ER)- and progesterone-receptor(PR)-negative tumours showed EGF positivity with equal frequency (P=0.05 in both). Axillary lymph node status, histological type, tumour size, histological grade, S-phase fraction, mitotic index or cancer recurrence did not show any statistical correlation with EGF expression. Tumour size (P=0.007), axillary lymph node involvement (P=0.003) and ER content (P=0.03) were independent prognostic factors in multivariate survival analysis, whereas EGF positivity, as an independent factor, had no effect on survival. In univariate analysis, however, EGF positivity predicted a more favourable outcome in axillary-lymph-node-positive tumours (P=0.04). The results suggest that immunohistochemical assessment of EGF expression has hardly any clinical significance in addition to the well-established prognostic factors in breast cancer.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Abbreviations
- EGF :
-
epidermal growth factor
- EGFR EGF :
-
receptor
References
Antoniotti S, Taverna D, Maggiora P, Sapei ML, Hynes NE, De Bortoli M (1994) Oestrogen and epidermal growth factor down-regulateerB-2 oncogene protein expression in breast cancer cells by different mechanisms. Br J Cancer 70: 1095–1101
Armstrong DK, Kaufmann SH, Ottaviano YL, Furga Y, Buckley JA, Isaacs JT (1994) Epidermal growth factor-mediated apoptosis of MDA-MB-468 human breast cancer cells. Cancer Res 54:5280–5283
Battaglia F, Scambia G, Rossi S, Panici PB, Bellantone R, Polizzi G, Querzoli P, Negrini R, Iacobelli S, Crucitti F, Mancuso S (1988) Epidermal growth factor receptor in human breast cancer: correlation with steroid hormone receptors and axillary lymph node involvement. Eur J Cancer Clin Oncol 11:1685–1690
Bhatavdekar JM, Patel DD, Karelia NH, Ghosh N, Shah NG, Balar DB, Trivedi SN (1994) Tumor markers in patients with advanced breast cancer as prognosticators: a preliminary study. Breast Cancer Res Treat 30:293–297
Bloom HJG, Richardson WW (1957) Histological grading and prognosis in breast cancer. Br J Cancer 11:359–377
Castellani R, Visscher DW, Wykes S, Sarkar FH, Crissman JD (1994) Interaction of transforming growth factor alpha and epidermal growth factor receptor in breast carcinoma. Cancer 2:344–349
Cox DR (1972) Regression models and life tables with discussion. J R Statist Soc[B] 34:187–220
Dickson RB, Salomon DS, Lippman ME (1991) Tyrosine kinase receptor-nuclear protooncogene interactions in breast cancer. Kluwer Academic, Boston
Freiss G, Vignon F (1994) Antiestrogens increase protein tyrosine phosphatase activity in human breast cancer cells. Mol Endocrinol 10:1389–1396
Haapasalo H, Pesonen E (1989) Volume corrected mitotic Index (M/V-index) The standard of mitotic activity in neoplasms. Pathol Res Pract 185:551–554
Hofland LJ, Van Den Burg B, Eijck CHJ van, Sprij DM, Koetsveld PM, Lamberts SWJ (1995) Role of tumor derived fibroblasts in the growth of primary cultures of human breast-cancer cells: effect of epidermal growth factor and the somatostatin analogue octreotide. Int J Cancer 60:93–99
Kirk J, Carmichael J, Stratford IJ, Harris AL (1994) Selective toxicity of TGF-alpha-PE40 to EGFR positive cell lines: selective protection of low EGFR-expressing cell lines by EGF. Br J Cancer 69:988–994
Klijn JGM, Berns PMJJ, Schmitz PJM, Foekens JA (1992) The clinical signification of epidermal growth factor receptor (EGFR) in breast cancer. A review on 5252 patients. Endocrine Rev 1:3–17
LeMaistre CF, Meneghetti C, Howes L, Osborne CK (1994) Targeting the EGF receptor in breast cancer treatment. Breast Cancer Res Treat 32:97–103
Mansour EG, Ravdin PM, Dressler L (1994) Prognostic factors in early breast carcinoma. Cancer 1:381–395
Martinazzi M, Crivelli F, Zampatti C, Martinazzi S (1993) Relationship between epidermal growth factor receptor (EGF-R) and other predictors of prognosis in breast carcinomas. Pathologica 85:637–644
Normanno N, Ciardiello F, Brandt R, Salomon DS (1994) Epidermal growth factor-related peptides in the pathogenesis of human breast cancer. Breast Cancer Res Treat 29:11–27
O'Sullivan C, Lewis CE, Harris AL, McGree J (1993) Secretion of epidermal growth factor by macrophages associated with breast carcinoma. Lancet 342:148–149
Pirinen R, Lipponen P, Syrjänen K (1995) Expression of epidermal growth factor receptor (EGFR) in breast cancer as related to clinical, prognostic and cytometric factors. Anticancer Res 15:2835–2840
Reddy KB, Mangold GL, Tandon AK, Yoneda T, Mundy GR, Zilberstein A, Osborne CK (1992) Inhibition of breast cancer cell growth in vitro by a tyrosine kinase inhibitor. Cancer Res 52:3636–3641
Taverna D, Antoniotti S, Maggiora P, Dati C, DeBortoli M, Hynes NE (1994) erB-2 expression in estrogen-receptor-positive breast tumor cells is regulated by growth-modulatory reagents. Int J Cancer 56:522–528
Van Agthoven T, Timmermans M, Foekens JA, Dorssers LCJ, Henzen-Logmans SC (1994) Differential expression of estrogen, progesterone, and epidermal growth factor receptors in normal benign, and malignant human breast tissues using dual staining immunohistochemistry. Am J Pathol 6:1238–1246
Veber N, Prevost G, Planchon P, Starzec A (1994) Evidence for growth effect of epidermal growth factor on MDA-MB-231 breast cancer cells. Eur J Cancer 9:1352–1359
Wellstein A (1994) Growth factor targeted and conventional therapy of breast cancer. Breast Cancer Res Treat 31:141–152
WHO (1981) Histological typing of breast tumors. International Histological classification of tumors, 2. World Health Organisation, Geneva
Wollman R, Yahalom J, Maxy R, Pinto J, Fuks Z (1994) Effect of epidermal growth factor on the growth and radiation sensitivity of human breast cancer cells in vitro. Int J Radiation Oncol Biol Phys 30:91–98
Yang J, Popnikolov NK, Sakthivel R, Nandi S (1994) Human breast cancers respond to growth factors in vivo but not in vitro. Cancer Lett 85:13–21
Yoshihisa U, Enokizono N, Sagara Y, Kuriwasi K, Takasaki T, Yoshida A, Yoshida H (1992) Immunohistochemical studies on oncogene products (EGF-R, c-erB-2) and growth factors (EGF, TGF-alpha) in human breast cancer: their relationship to oestrogen receptor status, histological grade, mitotic index and nodal status. Virchows Arch [A] 420:345–351
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Pirinen, R., Lipponen, P., Aaltomaa, S. et al. Prognostic value of epidermal growth factor expression in breast cancer. J Cancer Res Clin Oncol 123, 63–68 (1997). https://doi.org/10.1007/BF01212617
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01212617