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Prognostic significance of matrix metalloproteinases‐1, ‐2, ‐7 and ‐13 and tissue inhibitors of metalloproteinases‐1, ‐2, ‐3 and ‐4 in colorectal cancer
Author(s) -
Hilska Marja,
Roberts Peter J.,
Collan Yrjö U.,
Laine Veli Jukka O.,
Kössi Jyrki,
Hirsimäki Pirkko,
Rahkonen Otto,
Laato Matti
Publication year - 2007
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.22747
Subject(s) - colorectal cancer , stromal cell , matrix metalloproteinase , immunohistochemistry , pathology , staining , medicine , cancer , oncology , cancer research
Strong expression of many matrix metalloproteinases (MMPs) has been related to poor survival of colorectal cancer (CRC) patients. The expression of tissue inhibitors of metalloproteinases (TIMPs) has been associated with both a beneficial and a poor outcome and there is thus a need to further clarify the significance of MMPs and TIMPs in CRC. The prognostic significance of 4 MMPs and TIMPs in CRC was evaluated. Formalin‐fixed, paraffin‐embedded tissue arrayed samples of 351 patients with primary colon or rectal cancer of Dukes' stages A‐D were selected for immunohistochemical staining of MMP‐1, ‐2, ‐7 and ‐13, and TIMP‐1, ‐2, ‐3 and ‐4. High expression of MMP‐2 in the malignant epithelium as well as in the surrounding stroma was associated with reduced survival of colon cancer patients. Strong epithelial and stromal cytoplasmic staining of TIMP‐3 was associated with a longer survival in rectal cancer patients, and here the interobserver variation for evaluating the degree of staining was lower than for epithelial staining. Strong stromal cytoplasmic staining of TIMP‐4 predicted longer survival of rectal cancer patients. Multivariate analysis showed that stromal cytoplasmic TIMP‐3 staining was the only marker of independent prognostic value. MMP‐2 might be a useful prognostic marker in colon cancer, and TIMP‐3 and TIMP‐4 in rectal cancer, but the findings associated with stromal staining should be interpreted with some caution. Different biologic behavior or different genetic development may explain the differences between colon and rectal cancers regarding the expression of MMP‐2, TIMP‐3 and TIMP‐4. © 2007 Wiley‐Liss, Inc.