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Immunoexpression of metalloproteinase 14 and tissue inhibitor of metalloproteinase 2 in colorectal carcinomas and lymph node metastases

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Abstract

Changes in metalloproteinase (MMP) and tissue inhibitor of metalloproteinases (TIMP) have been associated with tumor progression in colorectal cancer. However, the role of MMP-14 and TIMP-2 has yet to be determined. We investigated the differential expression of MMP-14 and TIMP-2 in colorectal carcinomas of the left and the right colon, as well as in mononuclear cells in primary tumors and their lymph node metastases. We performed an immunohistochemistry analysis of tumor samples obtained from 50 cases of colorectal cancer. We found that MMP-14 staining was positive in 100 % of cases, in contrast to normal mucosa (86 % positivity, P = 0.0451). Additionally, neoplastic cells showed a higher frequency of TIMP-2-positive staining (70 % versus 14 % of normal mucosa, P = 0.0004). Furthermore, MMP-14 expression in primary tumor-associated mononuclear cells was higher in cases without lymph node metastases (N0) in comparison to more advanced carcinomas (N1–N3) (P = 0.0353). MMP-14 and TIMP-2 expression was observed in neoplastic cells in primary tumors, with a higher frequency of increased expression of MMP-14 (82 %) than increased expression of TIMP-2 (22 %, P < 0.0001). The expression of MMP-14 and TIMP-2 was evaluated in each cell type and at each site, and the frequency of TIMP-2 expression in colonic lesions and in the lymph nodes was significantly higher than in tumor-infiltrating mononuclear cells (P = 0.0003 and P = 0.0406, respectively). Expression of MMP-14 and TIMP-2 in primary colorectal carcinomas and in their lymph node metastases suggests the involvement of these proteins in local invasion and tumor progression.

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Acknowledgments

This work was supported by CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico), CAPES (Fundação Coordenação de Aperfeiçoamento de Pessoal de Nível Superior), and FUNCAP (Fundação Cearense de Apoio ao Desenvolvimento Científico). We are grateful to American Journal Experts for the English editing.

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The authors indicate no potential conflict of interest.

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Authors and Affiliations

  1. Department of Pathology and Forensic Medicine, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil

    Francisco Nélson Nóbrega Furtado, João Paulo Aguiar Sampaio, João Tarcisio Alves Maia-Filho, Renato Braga Vieira & Paulo Roberto Carvalho Almeida

  2. Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil

    Roberto César Pereira Lima-Júnior & Ronaldo Albuquerque Ribeiro

  3. Department of Clinical Oncology, Haroldo Juaçaba Hospital, Cancer Institute of Ceará, Fortaleza, Ceará, Brazil

    Ronaldo Albuquerque Ribeiro

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  1. Francisco Nélson Nóbrega Furtado
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  2. João Paulo Aguiar Sampaio
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  7. Paulo Roberto Carvalho Almeida
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Correspondence to Paulo Roberto Carvalho Almeida.

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Furtado, F.N.N., Sampaio, J.P.A., Maia-Filho, J.T.A. et al. Immunoexpression of metalloproteinase 14 and tissue inhibitor of metalloproteinase 2 in colorectal carcinomas and lymph node metastases. Comp Clin Pathol 24, 1367–1376 (2015). https://doi.org/10.1007/s00580-015-2085-0

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  • DOI: https://doi.org/10.1007/s00580-015-2085-0

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