C-myc oncogene product expression and prognosis in operable breast cancer

Abstract

Summary The 62 kDa protein product of the c-myc oncogene (p62 c-myc) is thought to be involved in the control of normal cellular proliferation and differentiation. We have measured oncoprotein levels using a flow cytometric assay in 141 operable breast cancers and have correlated levels with prognostic variables, patient survival and disease free intervals. High levels of p62 c-myc were associated with well differentiated tumours.There was no correlation with tumour DNA index, lymph node or oestrogen receptor status. C-myc oncoprotein levels were not predictive of patient survival or disease free interval. This relationship of oncoprotein levels with tumour histological grade is in keeping with the suggestion that the c-myc oncogene is important in the control of cellular differentiation. The other findings imply that measurement of c-myc oncoprotein levels does not yield useful prognostic information.Cellular oncogenes resembling viral oncogenes are present in normal cells where they encode proteins that act as receptors, intracellular signal transducers or growth factors. Oncogene products are thus important in the control of normal cellular development and division. Changes in oncogene expression occur during normal wound repair (Goyette et al., 1983) and embryogenesis (Muller et al., 1982). Changes in oncogene control and expression may also lead to, or be associated with, malignant transformation.The c-myc oncoprotein is associated with cell division and differentiation as c-myc mRNA increases as culture cells are stimulated into division (Kelly et al., 1983). It has a short half-life and has been shown to be nuclear associated (Persson & Leder, 1984), which is in keeping with a proposed role in cell cycle control. The aim of this study was to confirm that c-myc oncoprotein levels could be quantified in the nuclei of breast cancers. We also wished to determine whether a correlation existed between oncoprotein levels, tumour prognostic factors, patient survival and disease-free interval. Patients and methodsOne hundred and forty-one patients were studied. All had undergone simple or subcutaneous mastectomy as the primary treatment for their breast cancer between 1974 and 1976 at the Nottingham City Hospital. Lymph node sampling was performed in all cases. The nodes sampled were low axillary, apical axillary and internal mammary (via the second interspace) at the time of initial surgery. Three lymph node stages can be identified based on the involvement of nodes with metastatic tumour. These are: stage 1, no nodal involvement; stage 2, low axillary node involvement alone; stage 3, apical or internal mammary node involved alone or in any other combination.Antibodies to the c-myc oncoprotein have been generated by peptide immunisation . The DNA sequence of the c-myc gene was used to deduce the amino acid sequence of the oncoprotein, and mice were immunised to produce monoclonal antibodies. A number of antibodies have been produced and one of them can be used to detect p62 c-myc in archival pathological material...

Bmi-1, c-myc, and Snail expression in primary breast cancers and their metastases—elevated Bmi-1 expression in late breast cancer relapses

“…The controversy may be due to the differences in the scoring methods. Locker et al [48] did not find a correlation between axillary lymph node metastases and c-myc in their flow cytometric assay, but they reported that high levels of c-myc expression were found frequently in well-differentiated tumors.…”

Impact of c-MYC Protein Expression on Outcome of Patients with Early-Stage HER2+ Breast Cancer Treated with Adjuvant Trastuzumab NCCTG (Alliance) N9831

“…We observed nuclear MYC protein overexpression (defined as nuclear 3+ staining in >30% invasive cells) in tumors from 33% of N9831 patients with HER2+ breast cancer. Early studies using IHC have shown that ~ 50–100% of breast cancer cases have increased levels of MYC protein (5, 15, 18–23). In addition, strong MYC protein positivity was found in >20% nuclei in 45% of 440 primary breast tumors (24) and 70% (36/51) showed ≥1+ intensity staining (25) using the 9E10 clone employed in our present study.…”

The Nottingham prognostic index in primary breast cancer

“…These include histological grade [6], tumour type [45], ER status [9], binding of epithelial mucin antibodies [46], DNA index and SPF fraction [47], c-erbB-2 [48], c-myc [49], and Helix pomatia lectin binding [50]. Each relates to prognosis but also to grade, and in multivariate analysis, grade consistently emerges as the most powerful (and after its inclusion, the only) significant prognostic factor.…”