title: MMP-1 expression has an independent prognostic value in breast cancer.
abstract: BACKGROUND
  Breast cancer consists of a variety of tumours, which differ by their morphological features, molecular characteristics and outcome. Well-known prognostic factors, e.g. tumour grade and size, Ki-67, hormone receptor status, HER2 expression, lymph node status and patient age have been traditionally related to prognosis. Although the conventional prognostic markers are reliable in general, better markers to predict the outcome of an individual tumour are needed. Matrix metalloproteinase-1 (MMP-1) expression has been reported to inversely correlate with survival in advanced cancers. In breast cancer MMP-1 is often upregulated, especially in basal-type breast tumours. The purpose of this retrospective study was to analyse MMP-1 expression in breast cancer cells and in cancer associated stromal cells and to correlate the results with traditional prognostic factors including p53 and bcl-2, as well as to patient survival in breast cancer subtypes.
  
  
  METHODS
  Immunohistochemical analysis of MMP-1, ER, PR, Ki-67, HER2, bcl-2, p53 and CK5/6 expression was performed on 125 breast cancers. Statistical analyses were carried out using Kruskal-Wallis and Mann-Whitney -tests. In pairwise comparison Bonferroni-adjustment was applied. Correlations were calculated using Spearman rank-order correlation coefficients. Kaplan-Meier survival analyses were carried out to compare breast cancer-specific survival curves. Factors significantly associated with disease-specific survival in univariate models were included in multivariate stepwise.
  
  
  RESULTS
  Positive correlations were found between tumour grade and MMP-1 expression in tumour cells and in stromal cells. P53 positivity significantly correlated with MMP-1 expression in tumour cells, whereas HER2 expression correlated with MMP-1 both in tumour cells and stromal cells. MMP-1 expression in stromal cells showed a significant association with luminal A and luminal B, HER2 overexpressing and triple-negative breast cancer subtypes.
  
  
  CONCLUSIONS
  The most important finding of this study was the independent prognostic value of MMP-1 as well as Ki-67 and bcl-2 expression in tumour cells. Our study showed also that both tumoural and stromal MMP-1 expression is associated with breast tumour progression and poor prognosis. A significant difference of MMP-1 expression by cancer associated stromal cells in luminal A, luminal B and triple-negative breast cancer classes was also demonstrated.
authors.affiliation: University of Turku and Turku University Central Hospital, Department of Pathology, Kiinamyllynkatu 10, 20520 Turku, Finland. pia.bostrom@tyks.fi
authors.forename: Pia
authors.initials: P
authors.lastname: Boström
authors.forename: Mirva
authors.initials: M
authors.lastname: Söderström
authors.forename: Tero
authors.initials: T
authors.lastname: Vahlberg
authors.forename: Karl-Ove
authors.initials: KO
authors.lastname: Söderström
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Roberts
authors.forename: Olli
authors.initials: O
authors.lastname: Carpén
authors.forename: Pirkko
authors.initials: P
authors.lastname: Hirsimäki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000737:chemistry; D001943:Breast Neoplasms / Q000175:diagnosis / Q000201:enzymology* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000096:biosynthesis; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis* / Q000737:chemistry; D008875:Middle Aged; D060787:Neoplasm Grading; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D012189:Retrospective Studies; D018709:Statistics, Nonparametric; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D020781:Matrix Metalloproteinase 1; D019253:Proto-Oncogene Proteins c-bcl-2; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53; C495901:TP53 protein, human; C508053:ERBB2 protein, human