Immunohistochemical studies on oncogene products (EGF-R, c-erbB-2) and growth factors (EGF, TGF-α) in human breast cancer: their relationship to oestrogen receptor status, histological grade, mitotic index and nodal status

Abstract

In this investigation, 83 human mammary carcinomas were examined for the expression of oestrogen receptor (ER), epidermal growth factor receptor (EGF-R), epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), c-erbB-2, histological grade, mitotic index and nodal status, all of which are reportedly prognostically significant factors (Bloom and Richardson 1957; Baak et al. 1985; Wright et al. 1989). ER expression was biochemically recognized in 43.4% of mammary carcinomas, and EGF-R, EGF, TGF-alpha and c-erbB-2 were histochemically recognized in 25.3, 14.5, 27.7 and 18.0% of mammary carcinomas examined respectively, using conventional sections of buffered formalin-fixed, paraffin-embedded tissue and monoclonal or polyclonal antibodies. There were significant relationships between negative ER and positive EGF-R or TGF-alpha; positive EGF-R and TGF-alpha; positive EGF-R and c-erbB-2; and positive c-erbB-2 and TGF-alpha. The single changes which were the negative ER and the positive c-erbB-2 correlated with histological grade and mitotic index. Co-expression of EGF-R and TGF-alpha correlated with positive nodal status. Therefore, the present investigation indicates that the negative ER, single expression of c-erbB-2 and co-expression of EGF-R and TGF-alpha are important markers which contribute indirectly to prognosis, which reconfirms previous findings on the former two while adding the new finding that immunohistochemical demonstration of expression of EGF-R and TGF-alpha may provide useful information for selecting the appropriate treatment.

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.…”

Dominant negative Ras enhances lactogenic hormone‐induced differentiation by blocking activation of the Raf–Mek–Erk signal transduction pathway

“…The stimulation of mammary cells in culture by these growth factors activates signal transduction pathways that lead to cell survival and mitosis, and the activation of the EGF-R (ErbB1) correlates with aggressive behavior of breast tumors (Arteaga et al, 1988;Umekita et al, 1992). One of the signaling molecules activated by EGF family growth factors in breast tumors is the Ras GTPase (von Lintig et al, 2000).…”

Transforming growth factor alpha and mouse models of human breast cancer

“…Expression of TGFa has been identi®ed in pleural eusions from normal mammary gland (Arteaga et al, 1988), in invasive ductal carcinoma (Pilichowska et al, 1997) and correlates with increased neo-angiogensis (de Jong et al, 1998b) in breast tumors. Carcinomas of the breast that have higher level expression of TGFa also express high levels of EGFR, implicating a functional role for the TGFa/EGFR autocrine loop in tumors (Umekita et al, 1992). The correlation between levels of EGFR expression and neoplastic transformation in vivo is controversial (Gullick and Srinivasan, 1998).…”