title: Tumor progression driven by pathways activating matrix metalloproteinases and their inhibitors.
abstract: BACKGROUND
  Laryngeal squamous cell carcinoma (LSCC) is still a problem worldwide. In some publications interactions between the expression of matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, and their tissue inhibitors (TIMPs) implicated during cancer progression were suggested.
  
  
  METHODS
  The immunohistochemical staining using primary antibody against MMP-2, MMP-9, TIMP-1, TIMP-2, and TIMP-3 were performed. The research group consists of primary N(0) LSCC (20 cases), primary N(+) LSCC (17 cases), and 18 cases of normal mucosa.
  
  
  RESULTS
  Studied MMPs and TIMPs were localized in tumor cells and tumor stroma compartment. MMP-2 expression was higher in stroma compared to tumor cells. MMP-9, TIMP-1, TIMP-2, and TIMP-3 expression was higher in tumor cells than in tumor stroma (P < 0.05). In tumor stroma MMP-2, MMP-9, TIMP-1, and TIMP-3 expression, in LSCC N(0) vs. LSCC N(+) was significantly higher (P < 0.05). The ratios between MMP-2 and TIMP-3 expression were statistically significant (N(0) vs. N(+); P = 0.012). The analyses using classification trees predicted the probability of metastases according to TIMP-3/MMP-14/MMP-2 and MMP-9/TIMP-1 expression levels.
  
  
  CONCLUSIONS
  The presence of MMP-2, MMP-9, TIMP-1, TIMP-2, TIMP-3 expression in tumor cells and in tumor stroma, and additionally different expression according to lymph node involvement suggested of their impact during cancer progression. The significant correlation between TIMP-3 expression and the presence of lymph node metastases and MMP-2 expression might suggest the importance of TIMP-3 as a prognostic factor during tumor progression. The evaluation of molecular markers which participate in MMP-2 activation pathway have a major impact during metastasis.
authors.affiliation: Department of Clinical Pathomorphology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Bydgoszcz, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Bodnar
authors.affiliation: Department of Clinical Pathomorphology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Bydgoszcz, Poland.
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Szylberg
authors.affiliation: Department of Otolaryngology and Clinical Oncology Chair and Clinic of Otolaryngology and Department of Pathophysiology of Hearing and Balance System, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Bydgoszcz, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Kazmierczak
authors.affiliation: Department of Clinical Pathomorphology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Bydgoszcz, Poland.|Department of Oncologic Pathology, Poznan University of Medical Sciences and Greater Poland Oncology Center, Poznan, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Marszalek
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000473:pathology*; D005260:Female; D006258:Head and Neck Neoplasms / Q000201:enzymology* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007822:Laryngeal Neoplasms / Q000201:enzymology* / Q000473:pathology*; D008198:Lymph Nodes / Q000201:enzymology / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D020782:Matrix Metalloproteinases / Q000096:biosynthesis*; D008875:Middle Aged; D011379:Prognosis; D000077195:Squamous Cell Carcinoma of Head and Neck; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000096:biosynthesis; D019714:Tissue Inhibitor of Metalloproteinases / Q000096:biosynthesis*
chemical_list: C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; C088390:TIMP3 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019717:Tissue Inhibitor of Metalloproteinase-3; D019714:Tissue Inhibitor of Metalloproteinases; D019716:Tissue Inhibitor of Metalloproteinase-2; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: classification tree; laryngeal squamous cell carcinoma; matrix metalloproteinases; tissue inhibitors of matrix metalloproteinases; tumor microenvironment