Aggressive vestibular schwannomas showing postoperative rapid growth – their association with decreased p27 expression

Abstract

Vestibular schwannomas (VSs) are relatively slow growing tumors. However, some rapidly regrow or recur after surgical resection. The objective of this study was to identify those molecular characteristics predicting rapid recurrence after surgical resection. Immunohistochemically determined expressions of several cell cycle regulators and apoptosis-associated proteins in 12 cases of aggressive VS (AVS) and in 15 control cases of usual VS (UVS) cases were compared. The expressions of p53 and Bax (pro-apoptotic protein), Bcl-2 (anti-apoptotic protein), Fas, and Fas-L (apoptotic death receptor and ligand), caspase 3 (apoptotic effector caspase proteins), and p27 and p21 (cyclin-dependent kinase inhibitors) were analyzed using tissue array blocks. Loss of p27 expression was observed in 8 of 12 AVS cases (67%) and in 3 UVS cases (20%); p21 was expressed in all cases. Loss of Bax was observed in 3 AVS and 3 UVS cases. The anti-apoptotic protein, Bcl-2, was expressed in 9 AVS (75%) and 11 UVS (73%), and p53, Fas-L, and caspase 3 were negative and Fas was positive in all AVS and UVS cases. Of these, only the loss of p27 was statistically significant (P = 0.02). The loss of p27 in AVS may explain the unusually high proliferative potential of AVS versus UVS, and p27 may be a predictor of VS aggressiveness. The expressions of other apoptosis associated proteins were not significantly different in the two groups. This may be the first report to identify a molecular entity associated with aggressive VS. However, further studies are required.

Cyclin D1 Expression and Histopathologic Features in Vestibular Schwannomas

“…In a model of Wallerian nerve degeneration, mitotic response of Schwann cells was completely inhibited in cyclin D1 knockout mice, suggesting that cyclin D1 has a specific function in Schwann cell division (7). Seol et al (8) suggested that the loss of p27, a regulator of the cyclin D-CDK complexes during G1 to S-phase transition, may be a predictor of VS aggressiveness. In a recent study, Neff et al (4) found expression of cyclin D3 in 7 of 15 VS, whereas no cyclin D1 expression was found in any of these cases.…”

Tumor Microenvironment in Sporadic Vestibular Schwannoma: A Systematic, Narrative Review

“…Five records were unavailable for retrieving. Ninety-four articles were assessed for eligibility, and, in the end, 37 were included in the review [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 ]. A detailed flowchart of the search process is shown in Figure 1 .…”

YAP-Mediated Recruitment of YY1 and EZH2 Represses Transcription of Key Cell-Cycle Regulators

“…Our initial studies focused on CDKN1B, which codes for p27, and is a major regulator of the cell cycle that functions to prevent cells from entering S-phase (43) and is a regulator of Schwann cell differentiation (44,45). In addition, several studies report that p27 expression is downregulated in vestibular schwannomas (46,47). We find that YAP represses p27 through the recruitment of YY1 and the PRC2 complex (see model in Fig.…”