Stromal expression of matrix metalloprotease-9 in middle ear cholesteatomas.

BACKGROUND: Matrix metalloprotease-9 (MMP-9) plays an important role in the degradation of extracellular matrix (ECM). In cholesteatoma there are significant changes in the composition of the ECM, supporting the view of a disturbed cell-ECM interaction. It has been reported that in cholesteatoma tissues, MMP-9 is expressed in epithelial cells but not in stromal cells. In this study, we report conflicting results regarding the identity of the cholesteatoma cells that express MMP-9. METHODS: An immunohistochemical assay was performed to examine the expression of MMP-9 in 25 cases (formalin-fixed paraffin-embedded sections) of cholesteatoma, using an MMP-9-specific monoclonal antibody. RESULTS: In all cholesteatomas examined, MMP-9 was expressed in the stromal cells but not in the epithelial cells. MMP-9 immunostaining was undetectable in external auditory meatal skin (n = 5) and tympanic membrane (n = 3). CONCLUSIONS: These results suggest that the MMP-9 expressed in stromal cells may be involved in the disturbed cell-ECM interaction associated with the process of cholesteatoma formation.

Absence of nuclear p16 from Epstein-Barr virus-associated undifferentiated nasopharyngeal carcinomas.

OBJECTIVE: Epstein-Barr virus (EBV) is detected in the majority of undifferentiated nasopharyngeal carcinomas (UNPCs, World Health Organization type III). However, the exact mechanism involved in the carcinogenesis of EBV-associated UNPCs remains to be elucidated. An important unresolved question is: how is the normal cell cycle deregulated during EBV-associated UNPC development? The p16CDKN2 gene encodes a nuclear protein, p16, which inhibits the D-type cyclin/cyclin-dependent kinase complexes that phosphorylate the retinoblastoma gene product (pRb), thus blocking G1 cell cycle progression. The objective of this study was to determine whether p16 absence is involved in the development of EBV-associated UNPCs. METHODS: We performed immunohistochemistry to detect p16 and pRb and in situ hybridization to detect EBV-encoded small RNA (EBER) in UNPCs from 28 patients. RESULTS: No p16 was detected in 23 of 28 UNPCs (82.1%), whereas pRb was expressed in all those examined and EBER was detected in 22 of 28 (78.6%). The absence of p16 was associated with the presence of EBER in UNPCs (P < .0001): none of the 22 EBER+ UNPCs expressed p16, whereas 5 of 6 EBER- UNPCs did. CONCLUSION: Our data suggest that loss of p16-related cell cycle regulation plays an important role in the development of EBV-associated UNPCs.