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Expression of MMP-2, MMP-9 and TIMP-2 in pituitary tumors and their relationship with cavernous sinus invasion
Ane Caroline Thé B Freire1, Raquel S Jallad1, Rafael L Batista1
1Unidade de Neuroendocrinologia, Disciplina de Endocrinologia e Metabologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
Objective:
To evaluate the expression of matrix metalloproteinase-2 (MMP-2), MMP-9 and tissue inhibitor of metalloproteinase-2 (TIMP-2) in pituitary tumors and investigate their correlation with circulating plasma proteins and cavernous sinus invasion. In addition, the Ki-67 index was also assessed.
Methods:
Seventy-four patients (37 females) with pituitary adenomas were included, with preoperative peripheral blood collected in 29 cases. Tumor samples were evaluated for MMP-2, MMP-9, TIMP-2 and Ki-67 expression by immunohistochemistry. Protein plasma was semi-quantitatively detected using a commercial membrane antibody array.
Results:
Sixteen patients presented tumors invading the cavernous sinus. MMP-2 and TIMP-2 were slightly increased in these tumors compared to the noninvasive group, but the difference was not statistically significant. MMP-9 and TIMP-2 plasma concentrations did not correlate with tumor protein expression and also did not differ between the two groups. MMP-2 was not detected in plasma in any case. No statistically significant difference was observed when different tumor subtypes were considered. A significant difference was observed in tumor size (3.4 cm (2.8-4.9) vs 1.9 cm (1.3-2.6); P < 0.001) and in the Ki-67 index (1.8% (0.3-2.5) vs 0.5% (0.2-1.0); P = 0.01) between the invasive and noninvasive groups.
Conclusions:
In this cohort, we found no significant correlation between tissue and plasma levels of MMP-2, MMP-9 and TIMP-2 and cavernous sinus invasion in pituitary tumors. Further investigation is needed to elucidate the potential role of these markers in the invasiveness of pituitary tumors.
Insights
This study found no significant link between matrix metalloproteinase-2 (MMP-2), MMP-9, and tissue inhibitor of metalloproteinase-2 (TIMP-2) levels and cavernous sinus invasion in pituitary tumors. Further research is required to understand their role in tumor invasiveness.
Area of Science:
- Endocrinology
- Oncology
- Biochemistry
Background:
- Pituitary tumors can exhibit invasive behavior, impacting treatment and prognosis.
- Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are implicated in tumor invasion and metastasis.
- Understanding the role of MMP-2, MMP-9, and TIMP-2 in pituitary tumor invasion is crucial for developing targeted therapies.
Purpose of the Study:
- To evaluate the expression of MMP-2, MMP-9, and TIMP-2 in pituitary tumors.
- To investigate the correlation between these protein levels, circulating plasma proteins, and cavernous sinus invasion.
- To assess the Ki-67 index as a marker of tumor proliferation.
Main Methods:
- Immunohistochemistry was used to assess MMP-2, MMP-9, TIMP-2, and Ki-67 expression in 74 pituitary tumor samples.
- Preoperative peripheral blood was collected from 29 patients.
- Plasma protein levels were semi-quantitatively detected using a commercial membrane antibody array.
Main Results:
- No statistically significant difference in MMP-2 and TIMP-2 expression was found between tumors with and without cavernous sinus invasion.
- MMP-9 and TIMP-2 plasma concentrations did not correlate with tumor expression or invasion status.
- Tumor size and Ki-67 index were significantly higher in invasive tumors compared to noninvasive ones.
Conclusions:
- Tissue and plasma levels of MMP-2, MMP-9, and TIMP-2 showed no significant correlation with cavernous sinus invasion in pituitary tumors.
- The Ki-67 index and tumor size were associated with invasiveness.
- Further research is needed to clarify the role of these MMPs and TIMPs in pituitary tumor invasiveness.
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