Prognostic significance of mRNA-encoding estrogen receptor and epithelial growth factor receptor in breast carcinoma progression into lymph nodes: 1. Estrogen receptor encoding mRNA.
The main objective of this study was to differentiate between lymph nodes infiltrated by estrogen receptor-positive (ER+) and estrogen receptor-negative (ER-) breast carcinoma. Lymph nodes were obtained from 40 postmenopausal cancer patients, 10 from each disease stage. Six patients from each group had estrogen receptor-positive (BCaER+) and four estrogen receptor-negative (BCaER-) tumors. Both tumor-containing (T) and uninvolved (N) lymph nodes from the same patient were examined by the following parameters: magnitude of lymph node nucleic acid hybridization with cDNA probes from breast cancer MCF-7ER+ and MCF-7ER- cells; and binding capacity of 3H-estradiol, 125I-EGF, and 125I-PDGF binding and protein kinase C activities of the lymph nodes. Concomitant with the appearance of transformed cells, several events occur: Tumor cells induce stimulation of mononuclear cells and macrophages and evoke T- and B-cell proliferation, leading to the synthesis of tumor cell membrane-associated antibodies. In estrogen receptor-positive (ER+) breast carcinoma, estrogens and host hormonal modulatory mechanisms stimulate production and release of epithelial growth (EGF) and platelet-derived growth factors (PDGF). These factors are characterized by protein kinase C activities. There is infiltration of tumor cells into the lymph node and infiltration of leukocytes into the tumor site. In the lymph node, tumor progression depends on tumor cell proliferation rate and metastatic aggressiveness. The experiments described in this study document the changes that occur in lymph nodes, with differences between nodes infiltrated with BCaER+ and BCaER- breast carcinomas. Hybridization of 32P-cDNA from MCF-7ER+ cells with cellular RNA from BCaER+ involved (T) lymph nodes is greater than with cellular RNA from uninvolved (N) lymph nodes. The magnitude of hybridization correlated (P less than 0.005) with the disease stage.
Hakim
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Department of Medicine, Stritch School of Medicine, Evanston, Illinois.
D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D004247:DNA / Q000235:genetics; D066246:ErbB Receptors / Q000032:analysis / Q000235:genetics*; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D009693:Nucleic Acid Hybridization; D011379:Prognosis; D011493:Protein Kinase C / Q000378:metabolism; D015347:RNA Probes; D012333:RNA, Messenger / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000032:analysis / Q000235:genetics; D011960:Receptors, Estrogen / Q000032:analysis / Q000235:genetics*; D017479:Receptors, Platelet-Derived Growth Factor
D015347:RNA Probes; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011960:Receptors, Estrogen; D004247:DNA; D066246:ErbB Receptors; D017479:Receptors, Platelet-Derived Growth Factor; D011493:Protein Kinase C