Correlation of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinase expression in ileal carcinoids, lymph nodes and liver metastasis with prognosis and survival.

Voland, P; Besig, S; Rad, R; Braun, T; Baur, DM; Perren, A; Langer, R; Höfler, H; Prinz, C

doi:10.1159/000151482

User: Guest

journal article

Title:: Correlation of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinase expression in ileal carcinoids, lymph nodes and liver metastasis with prognosis and survival.
Document type:: Journal Article
Author(s):: Voland, P; Besig, S; Rad, R; Braun, T; Baur, DM; Perren, A; Langer, R; Höfler, H; Prinz, C
Abstract:: PURPOSE: Ileal carcinoids are gut epithelial tumors originating from serotonin-containing enterochromaffin (EC) cells. Therapeutic options for effectively inhibiting the growth and spread of metastatic carcinoids are still limited. We aimed to identify the role of matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs) during tumor development and metastasis. PATIENTS AND METHODS: Tissue samples were obtained from surgically treated patients. Expression of the EC-cell marker, vesicular monoamine transporter-1 (VMAT-1), was used to verify ileal carcinoids. We investigated the differential expression of MMP-2, 7, 9, 11, and 13 and their endogenous inhibitors (TIMP-1, 2, and 3) by quantitative real-time RT-PCR in 25 primary tumors, their corresponding lymph node metastases and/or liver metastases and matched normal mucosa. RESULTS: Significantly increased expression of VMAT-1, MMP-2, MMP-11, TIMP-1 and TIMP-3 was determined by quantitative RT-PCR in EC-cell carcinoids compared to normal intestinal mucosa (p < 0.05). In contrast, MMP-2 and MMP-9 as well as TIMP-1, TIMP-2, and TIMP-3 expression in primary tumors of patients with liver metastases (M1) was significantly lower than in patients lacking liver metastases (M0). EC-cell tumors were significantly larger in the M1 group of tumors, while VMAT-1 expression was significantly decreased. We found an inverse correlation between tumor size and prognosis. Univariate analysis further revealed that decreased expression of VMAT-1, MMP-2 and TIMP-3 in primary tumors was significantly associated with a reduced survival time of the patients. CONCLUSION: Our data reveal that MMP-2 and TIMP-3 expression together with VMAT-1 expression are of potential prognostic and clinical value in ileal carcinoids.
Journal title abbreviation:: Neuroendocrinology
Year:: 2009
Journal volume:: 89
Journal issue:: 1
Pages contribution:: 66-78
Language:: eng
Fulltext / DOI:: doi:10.1159/000151482
Pubmed ID:: http://view.ncbi.nlm.nih.gov/pubmed/18708724
Print-ISSN:: 0028-3835
TUM Institution:: II. Medizinische Klinik und Poliklinik (Gastroenterologie); Institut für Allgemeine Pathologie und Pathologische Anatomie
BibTeX