Expression of interleukin-6, interleukin-6 receptor, and glycoprotein 130 correlates with good prognoses for patients with breast carcinoma.
BACKGROUND
Interleukin-6 (IL-6) is secreted by normal epithelial breast cells but not by oncogene-transformed cells. Interleukin-6 is able to inhibit growth of breast carcinoma cells in culture. Interleukin-6 exerts its activity via two receptor subunits, IL-6R and glycoprotein 130 (gp130). The expression of these receptor subunits in breast tumors has been studied, but there are no previous reports of their prognostic significance, to the authors' knowledge.


METHODS
mRNA of IL-6, IL-6R, and gp130 was studied in 75 tumor samples obtained from breast carcinoma patients. Patients were followed for a maximum of 71 months (median follow-up, 61 months; 60 patients were followed for a minimum of 5 years or died during the observation period). Prognostic factors were analyzed in univariate and multivariate analysis.


RESULTS
mRNA specific to IL-6, IL-6R, and gp130 was detected in 57%, 53%, and 71% of breast carcinoma tissues, respectively. Expression was strongly correlated with earlier stages of the disease. In univariate analysis, expression of IL-6 and its receptor subunits proved to be a positive prognostic factor for overall survival (OS) and disease free survival (DFS). IL-6R and gp130 expression were good independent prognostic factors for OS. The 5-year OS of all patients was 66%. The 5-year OS in IL-6, IL-6R, and gp130 positive groups was 95%, 94%, and 90%, respectively, whereas in negative groups it was 26%, 31%, and 9%, respectively.


CONCLUSIONS
Expression of IL-6, IL-6R, and gp130 in breast carcinoma tissue is associated with earlier stages of the disease. In advanced stages, expression of IL-6 and its receptor subunits predicts better prognosis.
Karczewska
A
A
Department of Cancer Immunology, University School of Medical Sciences at Great Poland Cancer Center, Poznań.
Nawrocki
S
S
Breborowicz
D
D
Filas
V
V
Mackiewicz
A
A
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D015703:Antigens, CD / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D002277:Carcinoma / Q000235:genetics / Q000473:pathology*; D050822:Cytokine Receptor gp130; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000235:genetics; D019947:Receptors, Interleukin-6 / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D015996:Survival Rate; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; C494199:IL6ST protein, human; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D019947:Receptors, Interleukin-6; D050822:Cytokine Receptor gp130