title: Enhanced immunoreactivity of TIMP-2 in the stromal compartment of tumor as a marker of favorable prognosis in ovarian cancer patients.
abstract: Degradation of the extracellular matrix and basement membrane is a critical step in tumor progression. Matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase 2 (TIMP 2) act in a coordinated manner to form an integrated system involved in ovarian cancer (OC) progression. In this study, the authors describe the expression of TIMP-2 detected by immunohistochemistry in 6 OC cell lines and in 43 malignant epithelial ovarian tumors (in tumor and stromal compartments) in sections originating from primary laparotomies. No significant correlations between overall and progression-free survival and TIMP-2 expression in tumor compartment were observed. The analysis demonstrated a significant association between enhanced stromal expression of TIMP-2 and better clinical response to cisplatin- and paclitaxel-based chemotherapy. Increased expression of TIMP-2 in the stromal compartment and simultaneous overexpression in both stromal and tumor compartments strongly correlated with increased survival. No significant correlations were found in vitro between resistance to cisplatin, paclitaxel, or topotecan and the expression of TIMP-2 in the OC cell lines, suggesting stromal influences on tumor chemoresistance in the physiological environment. This study supports the concept of TIMP-2 expression in the stromal compartment of OC as a promising marker of prognosis and response to cisplatin- and paclitaxel-based chemotherapy in OC patients.
authors.affiliation: Department of Pathomorphology (AH,PD), Wroclaw Medical University, Wroclaw, Poland. ahalon2@gmail.com
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Hałoń
authors.forename: Ewa
authors.initials: E
authors.lastname: Nowak-Markwitz
authors.forename: Piotr
authors.initials: P
authors.lastname: Donizy
authors.forename: Rafal
authors.initials: R
authors.lastname: Matkowski
authors.forename: Adam
authors.initials: A
authors.lastname: Maciejczyk
authors.forename: Tserenchunt
authors.initials: T
authors.lastname: Gansukh
authors.forename: Balázs
authors.initials: B
authors.lastname: Györffy
authors.forename: Marek
authors.initials: M
authors.lastname: Spaczyński
authors.forename: Maciej
authors.initials: M
authors.lastname: Zabel
authors.forename: Hermann
authors.initials: H
authors.lastname: Lage
authors.forename: Pawel
authors.initials: P
authors.lastname: Surowiak
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000276:immunology*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology; D002451:Cell Compartmentation / Q000187:drug effects / Q000276:immunology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology; D011237:Predictive Value of Tests; D011379:Prognosis; D017154:Stromal Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; C560823:TIMP2 protein, human; D019716:Tissue Inhibitor of Metalloproteinase-2