Immunohistochemical Detection of Matrix Metalloproteinases (MMP) 1 and 2, and Tissue Inhibitor of Metalloproteinase 2 (TIMP 2) in Stage IB Cervical Cancer

Objective: Matrix metalloproteinases (MMPs) are a family of zinc-dependent metalloendopeptidases which participate in the degradation of collagen and other extracellular matrix macromolecules. Expression of gelatonic MMPs, such as MMP-2 has been linked to enhanced tumor invasion and metastases in in vitro and in vivo model systems. It was the aim of this study to determine whether the expression of MMP-1, MMP-2, and TIMP-2 correlates with survival in patients with surgically treated cervical cancer stage IB.

Methods: A sample of 154 paraffin-embedded tumor specimens of surgical treated FIGO stage IB cervical cancer was immunohistochemically investigated.

Results: MMP-1, MMP-2, and TIMP-2 were detected by immunohistochemistry in 74% (113/154), 32% (49/154), and 80% (107/154) of the tumor samples, respectively. Correlation coefficients for MMP-1/MMP-2, MMP-1/TIMP-2, MMP-2/TIMP-2 were 0.14 (p = 0.12), 0.37 (p = 0.0001), and 0.17 (p: 0.005), respectively. A significant correlation was found between MMP-1 and lymph node status (P < 0.01) and lymphvascular space invasion (P < 0.05). The expression of MMP-1 (log-rank test, p = 0.6), MMP-2 (log-rank test, p = 0.8), and TIMP-2 (log-rank test, p = 0.15) were not correlated with overall survival.

Conclusion: MMP-1, detected by immunohistochemistry, seems to play a role in the development of lymphvascular space invasion and lymph node metastases, but is not helpful in predicting the prognosis of cervical cancer patients.