bcl-2 in normal human breast and carcinoma, association with oestrogen receptor-positive, epidermal growth factor receptor-negative tumours and in situ cancer.
The role of bcl-2 expression in solid tumours is as yet undefined. It was, therefore, the purpose of this study to investigate expression of bcl-2 protein in 111 human breast carcinomas using immunohistochemistry and the monoclonal antibody bcl-2 124. Expression was then compared with the established indicators of prognosis and biological behaviour in malignant breast disease. No relationship could be observed between bcl-2 and node status, tumour size, differentiation, type or age at excision. However, a strong positive relationship was seen between bcl-2 and oestrogen receptor (ER), with 70 of 88 (80%) bcl-2-positive tumours being ER positive also, compared with seven of 23 (30%) bcl-2-negative tumours being ER positive (P < 0.0001). The converse was found when bcl-2 was compared with epidermal growth factor receptor (EGFR). A strong negative relationship was observed, with 26 of 88 (30%) bcl-2-positive tumours being EGFR positive, compared with 16 of 23 (70%) bcl-2-negative tumours being EGFR positive (P = 0.001), raising the possibility that bcl-2 is an ER-regulated gene. An inverse relationship was also found between bcl-2 and the oncogenes c-erbB-2 and p53. Thus, loss of bcl-2 expression in breast cancer is associated with a range of molecular markers of poor prognosis and may define part of an ER-negative, EGFR-positive phenotype.
Leek
R D
RD
Imperial Cancer Research Fund, University of Oxford, John Radcliffe Hospital, UK.
Kaklamanis
L
L
Pezzella
F
F
Gatter
K C
KC
Harris
A L
AL
D001940:Breast / Q000737:chemistry* / Q000502:physiology / Q000648:ultrastructure*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000648:ultrastructure*; D002278:Carcinoma in Situ / Q000737:chemistry* / Q000235:genetics / Q000648:ultrastructure*; D066246:ErbB Receptors / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D009376:Neoplasms, Hormone-Dependent / Q000737:chemistry* / Q000235:genetics / Q000648:ultrastructure*; D011518:Proto-Oncogene Proteins / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2; D011960:Receptors, Estrogen / Q000502:physiology*; D014018:Tissue Distribution; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics / Q000502:physiology
D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011960:Receptors, Estrogen; D016159:Tumor Suppressor Protein p53; D066246:ErbB Receptors