Expression and prognostic significance of metalloproteases and their inhibitors in luminal A and basal-like phenotypes of breast carcinoma.
To analyze the expression and prognostic value of matrix metalloproteases and their tissue inhibitors in luminal A and basal-like breast carcinomas, an immunohistochemical study was performed on cancer specimens from 93 randomly selected patients with invasive primary ductal tumors of the breast (46 with and 47 without distant metastasis) and with luminal A (n = 48) (ER+, HER2-) or basal-like (HER2-, ER-, PgR-) (n = 45) lesions. Luminal B cases were too few to analyze. Specimens were also studied using tissue microarrays and specific antibodies against matrix metalloproteases 1, 2, 7, 9, 11, 13, and 14 and tissue inhibitors 1, 2, and 3. There were no significant differences in matrix metalloprotease or tissue inhibitor expression in the 2 phenotypes of tumors. In basal-like carcinomas, high scores for matrix metalloproteases 9 and 11 were significantly associated with a high distant metastasis rate. Likewise, data showed associations between matrix metalloprotease/tissue inhibitor expression by either stromal fibroblasts or mononuclear inflammatory cells and distant relapse-free survival in both tumor phenotypes. In addition, in infiltrating luminal A and basal-like tumors, we identified a prometastatic phenotype of mononuclear inflammatory cells, showing a high matrix metalloprotease/tissue inhibitor molecular profile. Expression of matrix metalloproteases and tissue inhibitors is related to the characteristics of breast tumor cells. As prognostic factors in breast carcinomas of both luminal A and basal-like phenotypes, our results point to the importance of the expression of matrix metalloproteases and tissue inhibitors by the stromal cells.
Unidad de Investigación, Hospital de Jove, 33290 Gijón, Spain.
Luis O
LO
González
María D
MD
Corte
Sara
S
Junquera
Raquel
R
González-Fernández
José M
JM
del Casar
Carmen
C
García
Alejandro
A
Andicoechea
Julio
J
Vázquez
Román
R
Pérez-Fernández
Francisco J
FJ
Vizoso
D001365:Axilla / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D053555:Keratin-5 / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008198:Lymph Nodes / Q000473:pathology; D045726:Metalloproteases / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D010641:Phenotype; D011379:Prognosis; D040081:Protein Array Analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D016019:Survival Analysis; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D053555:Keratin-5; D019394:Ki-67 Antigen; D045726:Metalloproteases; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D019714:Tissue Inhibitor of Metalloproteinases; D016159:Tumor Suppressor Protein p53