Expression of Matrix Metalloproteinase 2 (MMP-2) and Tissue Inhibitor of Metalloproteinase 2 (TIMP-2) in Medullary Thyroid Carcinoma: Prognostic Implications

Cavalheiro, Beatriz G.; Junqueira, Consuelo Rodrigues; Brandão, Lenine Garcia

doi:10.1089/thy.2007.0412

Cited by 23 publications

(25 citation statements)

References 33 publications

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“…In previous research,39,40 we observed a correlation between prognosis and the immunohistochemical expressions of metalloproteinases—enzymes related to the extracellular matrix and basement membrane degradation—in MTC surgical specimens. However, statistical parameters, such as sensitivity and specificity, showed that the presence of cervical lymph node metastases and TNM stage were the major variables.…”

Section: Discussionmentioning

confidence: 66%

Prognostic Influence of Clinical and Pathological Factors in Medullary Thyroid Carcinoma: A Study of 53 Cases

Brandão

Cavalheiro

Junqueira

2009

Clinics

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OBJECTIVES AND INTRODUCTIONMedullary thyroid carcinoma, a neoplasia of intermediate prognosis and differentiation, does not always respond predictably to known treatments. This study aimed to correlate the clinical progression of surgically treated patients with clinical and pathological data.METHODSA total of 53 patients were followed for 75 months (mean average) in tertiary-care hospital. The clinical status of patients at the end of the study period was characterized to determine correlations with a range of disease aspects. A value of p < 0.05 was considered statistically significant.RESULTSTwenty-two patients (41.5%) were alive and disease-free at the end of the follow-up period; twenty-three patients (43.4%) had persistent disease; and eight patients (15.1%) had recurrent disease. Four patients (7.6%) died from medullary thyroid carcinoma with clinical and/or imaging evidence of neoplasia. The following aspects demonstrated statistically significant correlations with the final medical condition: positive initial cervical examination (p = 0.002); neoplastic extensions to the thyroid capsule (p = 0.004) and adjacent tissues (p = 0.034); cervical lymph node metastases (p < 0.001); diameter of neoplasia (p = 0.018); TNM (tumor, node and metastasis) Stage (p = 0.001) and evidence of distant and/or cervical diseases in the absence of a cure (p = 0.011). Through logistic regression, the presence of cervical lymph node metastases was considered an independent variable (p < 0.001).CONCLUSIONSClinical and pathological aspects of patients with surgically treated medullary thyroid carcinomas are predictors of disease progression. Specifically, even treated cervical lymph node metastases are significantly correlated with disease progression.

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Section: Discussionmentioning

confidence: 66%

Prognostic Influence of Clinical and Pathological Factors in Medullary Thyroid Carcinoma: A Study of 53 Cases

Brandão

Cavalheiro

Junqueira

2009

Clinics

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“…Production of proMMP2 and MT1-MMP has previously been shown in human PTC and MT1-MMP expression levels correlated with the proMMP2 activation ratio, thyroid cancer cell invasion, and PTC lymph node metastasis (31,35). Similarly, a positive correlation was reported for the presence of immunoreactive MMP2, but not TIMP2, and bad prognosis of patients with medullary thyroid cancer, a tumor derived from C-cells in the thyroid gland (51). Expression of gelatinase A (MMP2), gelatinase B (MMP9), and MT-MMP1 has also been reported in breast, colon, lung, skin, ovary, and prostate cancer and is associated with enhanced invasion and decreased overall survival (52)(53)(54).…”

Section: Discussionmentioning

confidence: 73%

Relaxin Enhances the Collagenolytic Activity and In Vitro Invasiveness by Upregulating Matrix Metalloproteinases in Human Thyroid Carcinoma Cells

Białek

Kunanuvat

Hombach‐Klonisch

et al. 2011

Molecular Cancer Research

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In this study, we identified differential expression of immunoreactive matrix metalloproteinase 2 (MMP2)/ gelatinase A, membrane-anchored MT1-MMP/MMP14, and human relaxin-2 (RLN2) in human benign and malignant thyroid tissues. MMP2 and MT1-MMP were detected in the majority of thyroid cancer tissues and colocalized with RLN2-positive cells. MMP2 was mostly absent in goiter tissues and, similar to RLN2, may serve as a marker for thyroid cancer. MMP2 and MT1-MMP were identified as novel RLN2 targets. RLN2 caused a significant downregulation of tissue inhibitor of MMP (TIMP) 3 protein levels but did not change the expression levels of MMP13, and TIMP1, TIMP2, and TIMP4 in human thyroid carcinoma cells. RLN2 failed to affect the expression of MMP1, 3, 8, and 9 in the thyroid carcinoma cells investigated. Stable RLN2 transfectants secreted enhanced levels of bioactive MMP2 which contributed to the increased collagenolytic activity and in vitro invasiveness into collagen matrix by human thyroid cancer cells. Three-dimensional reconstitution of confocal fluorescent microscopy images revealed larger-sized invadopodia, with intense MT1-MMP accumulation at the leading migrating edge in RLN2 transfectants when compared with enhanced green fluorescent protein clones. In RLN2 transfectants actin stress fibers contributed to pseudopodia formation. In conclusion, enhanced tumor cell invasion by RLN2 involves the formation of MT1-MMP-enriched invadopodia that lead to increased collagenolytic cell invasion by human thyroid cancer cells. Mol Cancer Res; 9(6); 673-87. Ó2011 AACR.

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“…Two transcript variants encoding different isoforms have been found for this gene. A recent study assessing a panel of MTC cancer specimens found that expression of MMP2 could be used as a prognostic tool (Cavalheiro et al, 2008). …”

Section: Genes Involved and Proteinsmentioning

confidence: 99%

Thyroid: Medullary carcinoma

Somnay¹,

Mazeh²

2013

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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Expression of Matrix Metalloproteinase 2 (MMP-2) and Tissue Inhibitor of Metalloproteinase 2 (TIMP-2) in Medullary Thyroid Carcinoma: Prognostic Implications

Abstract: Immunohistochemical expression of MMP-2 in thyroid surgical specimens from patients with MTC is a novel indicator of the prognosis of this cancer.

Cited by 23 publications

References 33 publications

Prognostic Influence of Clinical and Pathological Factors in Medullary Thyroid Carcinoma: A Study of 53 Cases

Prognostic Influence of Clinical and Pathological Factors in Medullary Thyroid Carcinoma: A Study of 53 Cases

Relaxin Enhances the Collagenolytic Activity and In Vitro Invasiveness by Upregulating Matrix Metalloproteinases in Human Thyroid Carcinoma Cells

Thyroid: Medullary carcinoma

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