title: Worse prognosis in breast cancer patients can be predicted by immunohistochemical analysis of positive MMP-2 and negative estrogen and progesterone receptors.
abstract: Breast cancer is the most cause of death, and approximately 90% of these deaths are due to metastases. Matrix metalloproteinase-2 (MMP-2) gelatinase activity is able to degrade a major constituent of the tumor microenvironment, type IV collagen. Two well-established proteins used as markers in clinical practice for breast cancer are the receptors for estrogen (ER) and progesterone (PR). Although the presence of these receptors has been associated with a better prognosis, loss of these proteins can occur during tumor progression, with subsequent resistance to hormone therapy.
  To study the correlation among MMP-2, ER, and PR, as well as the establishment of the metastatic process in primary breast tumors.
  Breast cancer samples (n=44) were analyzed by immunohistochemistry for MMP-2, ER, and PR.
  We observed that 90% of patients who had metastases and died showed positive staining for MMP-2 (p=0.0082 for both). Using Kaplan-Meier analysis, we found that negative ER patients who were also positive for MMP-2 had even worse disease-free survival (DFS) and overall survival (OS) (p= 0.012 and p=0.005, respectively). Similar results were found in PR-negative patients for DFS (a trend p=0.077) and OS (p=0.038).
  Regardless of our small sample size (n=44), the data obtained strongly suggest that MMP-2 in combination with already well-established markers could help to predict the emergence of metastases and death in patients with breast cancer.
authors.affiliation: Department of Basic Pathology, Universidade Federal do Paraná (UFPR), Curitiba, PR, Brazil.
authors.forename: Edneia A S
authors.initials: EA
authors.lastname: Ramos
authors.affiliation: Department of Basic Pathology, Universidade Federal do Paraná (UFPR), Curitiba, PR, Brazil.
authors.forename: Camila T da
authors.initials: CT
authors.lastname: Silva
authors.affiliation: Department of Basic Pathology, Universidade Federal do Paraná (UFPR), Curitiba, PR, Brazil.
authors.forename: Graciele C M
authors.initials: GC
authors.lastname: Manica
authors.affiliation: Department of Basic Pathology, Universidade Federal do Paraná (UFPR), Curitiba, PR, Brazil.
authors.forename: Isabela T
authors.initials: IT
authors.lastname: Pereira
authors.affiliation: Department of Basic Pathology, Universidade Federal do Paraná (UFPR), Curitiba, PR, Brazil.
authors.forename: Liliane M B
authors.initials: LM
authors.lastname: Klassen
authors.affiliation: Department of Genetic, UFPR, Curitiba, PR, Brazil.
authors.forename: Enilze M S F
authors.initials: EM
authors.lastname: Ribeiro
authors.affiliation: Department of Genetic, UFPR, Curitiba, PR, Brazil.
authors.forename: Iglenir J
authors.initials: IJ
authors.lastname: Cavalli
authors.affiliation: Department of Basic Pathology, Universidade Federal do Paraná (UFPR), Curitiba, PR, Brazil.
authors.forename: Karin
authors.initials: K
authors.lastname: Braun-Prado
authors.affiliation: Hospital Nossa Senhora das Graças, Curitiba, PR, Brazil.
authors.forename: Rubens S
authors.initials: RS
authors.lastname: Lima
authors.affiliation: Hospital Nossa Senhora das Graças, Curitiba, PR, Brazil.
authors.forename: Cicero A
authors.initials: CA
authors.lastname: Urban
authors.affiliation: Cancer Biology and Epigenomics Program, Ann and Robert Lurie Children's Hospital of Chicago Research Center and Department of Pediatrics, Northwestern University's Feinberg School of Medicine, Chicago, IL, 60614, USA.
authors.forename: Fabrício F
authors.initials: FF
authors.lastname: Costa
authors.affiliation: Department of Experimental Pathology, Pontifícia Universidade Católica do Paraná (PUC-PR), Curitiba, PR, Brazil.
authors.forename: Lucia de
authors.initials: L
authors.lastname: Noronha
authors.affiliation: Department of Basic Pathology, Universidade Federal do Paraná (UFPR), Curitiba, PR, Brazil.
authors.forename: Giseli
authors.initials: G
authors.lastname: Klassen
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001938:Brazil / Q000453:epidemiology; D001943:Breast Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D020778:Matrix Metalloproteinase 2 / Q000032:analysis*; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D011960:Receptors, Estrogen / Q000032:analysis*; D011980:Receptors, Progesterone / Q000032:analysis*
chemical_list: D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D020778:Matrix Metalloproteinase 2