Expression of RECK and matrix metalloproteinase-2 in ameloblastoma

Abstract

Background: Ameloblastoma is a frequent odontogenic benign tumor characterized by local invasiveness, high risk of recurrence and occasional metastasis and malignant transformation. Matrix metalloproteinase-2 (MMP-2) promotes tumor invasion and progression by destroying the extracellular matrix (ECM) and basement membrane. For this proteolytic activity, the endogenous inhibitor is reversion-inducing cysteine rich protein with Kazal motifs (RECK). The aim of this study was to characterize the relationship between RECK and MMP-2 expression and the clinical manifestation of ameloblastoma.

Methods: Immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) were employed to detect the protein and mRNA expression of RECK and MMP-2 in keratocystic odontogenic tumor (KCOT), ameloblastoma and ameloblastic carcinoma.

Results: RECK protein expression was significantly reduced in KCOT (87.5%), ameloblastoma (56.5%) and ameloblastic carcinoma (0%) (P < 0.01), and was significantly lower in recurrent ameloblastoma compared with primary ameloblastoma (P < 0.01), but did not differ by histological type of ameloblastoma. MMP-2 protein expression was significantly higher in ameloblastoma and ameloblastic carcinoma compared with KCOT (P < 0.01). RECK mRNA expression was significantly lower in ameloblastoma than in KCOT (P < 0.01), lower in recurrent ameloblastoma than in primary ameloblastoma, and was negative in ameloblastic carcinoma. MMP-2 mRNA expression was significantly higher in ameloblastoma compared with KCOT (P < 0.01), but was no different in recurrent ameloblastoma versus primary ameloblastoma. RECK protein expression was negatively associated with MMP-2 protein expression in ameloblastoma (r = -0.431, P < 0.01).

Conclusion: Low or no RECK expression and increased MMP-2 expression may be associated with negative clinical findings in ameloblastoma. RECK may participate in the invasion, recurrence and malignant transformation of ameloblastoma by regulating MMP-2 at the post-transcriptional level.

Figure 1

A representative immunohistochemical reactivity for RECK. (A) Keratocystic odontogenic tumor showing strong reactivity (× 400); (B) Follicular ameloblastoma showing strong reactivity in central polyhedral cells and weak in peripheral columnar cells (× 200); (C) Plexiform ameloblastoma showing reactivity in peripheral columnar cells and nearly no expression in central polyhedral cells (× 200); (D) Ameloblastic carcinoma showing no expression in tumor cells (× 400).

Figure 2

A representative immunohistochemical reactivity for MMP-2. (A) Keratocystic odontogenic tumor showing moderate reactivity in prickle cells (× 400); (B) Follicular ameloblastoma showing strong reactivity in peripheral columnar cells (× 400); (C) Plexiform ameloblastoma showing strong reactivity in peripheral columnar cells (× 200); (D) Ameloblastic carcinoma showing strong reactivity in tumor cells (× 400).

Figure 3

Representative gel pictures showing the mRNA expression of RECK and MMP-2. M, DNA marker; 1 and 2, Keratocystic odontogenic tumor; 3 and 4, Ameloblastoma; 5, Ameloblastic carcinoma.