Correlation of c-erbB-2 gene amplification and protein expression in human breast carcinoma with nodal status and nuclear grading.

Fifty-one primary human breast tumors were analyzed for amplification of the c-erbB-2 protooncogene. Thirteen (25%) of the DNA samples contained multiple gene copies. Paraffin-embedded tumor sections, available from 47 of the cases, were stained with a c-erbB-2 specific antiserum. Eighty-three % (10 of 12) of the tumors containing amplified c-erbB-2 gene copies stained positively with the c-erbB-2 specific antiserum (P = 0.03). Thirteen tumors containing single copy c-erbB-2 sequences also stained positively with the antiserum. This suggests that mechanisms other than gene amplification may lead to elevated levels of c-erbB-2 protein. Finally, there was a statistically significant correlation between c-erbB-2 protein expression and parameters used in breast cancer prognosis. Positive staining was associated with positive nodal status of the patient (P = 0.02) and with tumors showing a poor nuclear grade (P = 0.02). This is the first study showing that a determination of the level of c-erbB-2 protein in paraffin-embedded tumor sections may have prognostic value for the course of human breast cancer.

[1]  Sauer,et al.  Breast Diseases , 1989, Springer Berlin Heidelberg.

[2]  W. Cavenee,et al.  Loss of heterozygosity in human ductal breast tumors indicates a recessive mutation on chromosome 13. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[3]  M. Berger,et al.  Expression of the c‐erbB‐2 protein in normal and transformed cells , 1987, International journal of cancer.

[4]  W. Gullick,et al.  OVEREXPRESSION OF THE c-erbB-2 ONCOPROTEIN IN HUMAN BREAST CARCINOMAS: IMMUNOHISTOLOGICAL ASSESSMENT CORRELATES WITH GENE AMPLIFICATION , 1987, The Lancet.

[5]  C R King,et al.  erbB-2 is a potent oncogene when overexpressed in NIH/3T3 cells. , 1987, Science.

[6]  M. Kraus,et al.  Overexpression of the EGF receptor‐related proto‐oncogene erbB‐2 in human mammary tumor cell lines by different molecular mechanisms. , 1987, The EMBO journal.

[7]  W. McGuire,et al.  Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. , 1987, Science.

[8]  R. Weinberg,et al.  Inhibition of tumor growth by a monoclonal antibody reactive with an oncogene-encoded tumor antigen. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[9]  T. Yamamoto,et al.  The product of the human c-erbB-2 gene: a 185-kilodalton glycoprotein with tyrosine kinase activity. , 1986, Science.

[10]  Cori Bargmann,et al.  Multiple independent activations of the neu oncogene by a point mutation altering the transmembrane domain of p185 , 1986, Cell.

[11]  I. Pastan,et al.  Human multidrug-resistant cell lines: increased mdr1 expression can precede gene amplification. , 1986, Science.

[12]  R. Weinberg,et al.  p185, a product of the neu proto-oncogene, is a receptorlike protein associated with tyrosine kinase activity , 1986, Molecular and cellular biology.

[13]  M. Schwab,et al.  Oncogene amplification in tumor cells. , 1986, Advances in cancer research.

[14]  P. Seeburg,et al.  Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene. , 1985, Science.

[15]  H. Sather,et al.  Association of multiple copies of the N-myc oncogene with rapid progression of neuroblastomas. , 1985, The New England journal of medicine.

[16]  K. Semba,et al.  A v-erbB-related protooncogene, c-erbB-2, is distinct from the c-erbB-1/epidermal growth factor-receptor gene and is amplified in a human salivary gland adenocarcinoma. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[17]  R. Weinberg,et al.  The neu gene: an erbB-homologous gene distinct from and unlinked to the gene encoding the EGF receptor. , 1985, Science.

[18]  C R King,et al.  Amplification of a novel v-erbB-related gene in a human mammary carcinoma. , 1985, Science.

[19]  J. Chebath,et al.  Structure of two forms of the interferon‐induced (2′‐5′) oligo A synthetase of human cells based on cDNAs and gene sequences. , 1985, The EMBO journal.

[20]  Hermona Soreq,et al.  Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin , 1985, Nature.

[21]  R. Weinberg,et al.  The neu oncogene: an erb-B-related gene encoding a 185,000-Mr tumour antigen , 1984, Nature.

[22]  E. Chen,et al.  Human transforming growth factor-α: Precursor structure and expression in E. coli , 1984, Cell.

[23]  H. Varmus,et al.  Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage. , 1984, Science.

[24]  C. Muir,et al.  Estimates of the worldwide frequency of twelve major cancers. , 1984, Bulletin of the World Health Organization.

[25]  D. Zava Interlaboratory variability in the determination of estrogen receptor and progesterone receptor content in human breast tumors: quality control in Switzerland. , 1984, Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer.

[26]  E. Chen,et al.  Human transforming growth factor-alpha: precursor structure and expression in E. coli. , 1984, Cell.

[27]  F. Alt,et al.  Transposition and amplification of oncogene-related sequences in human neuroblastomas , 1983, Cell.

[28]  J. Trent,et al.  Amplified DNA with limited homology to myc cellular oncogene is shared by human neuroblastoma cell lines and a neuroblastoma tumour , 1983, Nature.

[29]  S. Aaronson,et al.  Transforming genes of human hematopoietic tumors: frequent detection of ras-related oncogenes whose activation appears to be independent of tumor phenotype. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[30]  O. Mcbride,et al.  Molecular cloning and chromosomal mapping of a human locus related to the transforming gene of Moloney murine sarcoma virus. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[31]  P. Saigo,et al.  Axillary Micro- and Macrometastases in Breast Cancer: Prognostic Significance of Tumor Size , 1981, Annals of surgery.

[32]  S. Hsu,et al.  The use of antiavidin antibody and avidin-biotin-peroxidase complex in immunoperoxidase technics. , 1981, American journal of clinical pathology.

[33]  B. Groner,et al.  Number and location of mouse mammary tumor virus proviral DNA in mouse DNA of normal tissue and of mammary tumors , 1980, Journal of virology.

[34]  P Berg,et al.  Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. , 1977, Journal of molecular biology.

[35]  E. Southern Detection of specific sequences among DNA fragments separated by gel electrophoresis. , 1975, Journal of molecular biology.