COX2 expression is associated with preoperative tumor volume but not with volumetric tumor growth in vestibular schwannoma

Abstract

Objective Vestibular schwannomas (VS) are benign slow growing tumors arising from the vestibular nerve. The role of cyclooxygenase 2 (COX2) in tumor development of growth has been addressed in a few studies with contradictory results and suggestions. We recently analyzed the immunohistochemical expression of COX2 in 1044 VS samples and described an association of higher COX2 expression with proliferation but found no influence by regular intake of acetylsalicylic acid. We now collected volumetric radiographic data of the preoperative tumor volume and growth to further test the role of COX2 in VS growth. Methods Preoperative images of 898 primary sporadic vestibular schwannomas were assessed, and sufficient preoperative imaging was used for the volumetric measurement preoperative tumor volume (n = 747) and preoperative relative tumor growth (n = 171). Clinical parameters and results of the immunohistochemical expression of COX2 and MIB1 in resected tumor tissue samples were obtained from our prior study. ANOVA, CART-analysis and multivariate nominal logistic regression were used for statistical analysis. Results Larger preoperative tumor volumes were observed with tumors of younger patients (p = 0.0288) and with higher COX2 expression scores (p < 0.0001). Higher MIB1 expression was associated with smaller tumors (p = 0.0149) but with increased radiographic tumor growth (p = 0.0003). Patients of older age had tumors with slower growth rates (p = 0.0311). In the multivariate analysis only MIB1 expression was an independent significant factor regarding tumor growth (p = 0.0002). Conclusions Higher expression of COX2 in schwannoma is associated with an increased preoperative tumor volume but not with radiographic tumor growth over time.

Vestibular Schwannoma Volume and Tumor Growth Correlates with Macrophage Marker Expression

“…In addition, a positive correlation between COX2 expression and tumor extension (Hannover classification) in 1048 VS was detected by IHC [ 19 ]. However, no increase in COX2 expression was found with an increasing volumetric growth rate [ 25 ]. Treatment with COX2 inhibitors did not affect COX2 expression and VS- growth [ 19 ].…”

“…Koutsimpelas et al examined a positive correlation between proliferation index and tumor diameter in 182 sporadic VS [ 18 ]. In contrast to this, analysis of 747 VS showed increasing Ki-67 expression in smaller tumors and VS with a higher growth rate [ 25 ]. In contrast to the previous study, our study showed lower expression of Ki-67 in large VS and in fast-growing VS. Abundant Ki-67 expression was also detected in the IHC sections of the smaller VS.…”

Transition of a vestibular schwannoma to a malignant peripheral nerve sheath tumor with loss of H3K27 trimethylation after radiosurgery—a case report and review of the literature

“…In comparison, the series of our department with 1381 vestibular schwannomas included only 202 patients of that age category (14.6%). We recently showed in a retrospective analysis that younger patients, suffering from sporadic VS, had larger tumor volumes and higher volumetric tumor growth rates prior to surgery [ 45 ] suggesting that sporadic VS developing at a younger age may behave differently. Furthermore, a more cautious indication for radiosurgery for vestibular schwannomas in NF2 patients has already been suggested [ 8 ].…”

Skull Base Tumors: The Equilibrium between Curation and Preservation

“…One hypothesis is based on an inflammatory component being predominant in growing VS. Leisz et al reported interesting results in their cohort, demonstrating a positive correlation between macrophage marker (CD68 and CD163) expression and VS volume and growth rate [11]. However, COX2, Ki-67, and VEGF expression were all negatively correlated with large VS and fastgrowing tumors, contradicting previous studies [12,13]. One explanation is an increased recruitment of M2 macrophages in active, growing VS, leading to swelling and escalating growth [14].…”