COX2 expression is associated with proliferation and tumor extension in vestibular schwannoma but is not influenced by acetylsalicylic acid intake

Abstract

Acetylsalicylic acid has been linked to a lower risk for different cancer types, presumably through its inhibitory effect on cyclooxygenase 2. This has also been investigated in vestibular schwannomas with promising results suggesting an antiproliferative effect and recently the intake has been recommended for vestibular schwannomas as a conservative treatment option. We constructed tissue microarrays from paraffin-embedded tissue samples of 1048 vestibular schwannomas and analyzed the expression of cyclooxygenase 2 and the proliferation marker MIB1 (Molecular Immunology Borstel) via immunohistochemistry together with clinical data (age, gender, tumor extension, prior radiotherapy, neurofibromatosis type 2, tumor recurrence, cyclooxygenase 2 responsive medication). Univariate analysis showed that cyclooxygenase 2 expression was increased with age, female gender, prior radiotherapy and larger tumor extension. MIB1 expression was also associated with higher cyclooxygenase 2 expression. Schwannomas of neurofibromatosis type 2 patients had lower cyclooxygenase 2 levels. Use of acetylsalicylic acid, non-steroidal anti-inflammatory drugs, glucocorticoids or other immunosuppressants did not show differences in cyclooxygenase 2 or MIB1 expression. Instead, cyclooxygenase 2 expression increases with tumor extension while MIB1 expression is not associated with tumor size. Overall, cyclooxygenase 2 expression is associated with proliferation but not influenced by regular intake of acetylsalicylic acid or other cyclooxygenase 2-responsive medications. Acetylsalicylic acid intake does not alter cyclooxygenase 2 expression and has no antiproliferative effect in vestibular.

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

“…Our data indicate that COX2-mediated inflammatory processes in vestibular schwannoma do not influence tumor growth. Thus, the recommendation to control tumor growth conservatively with acetyl salicylic acid via COX2 Regarding the preoperative tumor volume, relative higher COX2 expression is associated with larger vestibular schwannoma volume, which was already suggested in our prior study where a correlation of COX2 expression and the tumor extension (Hannover classification) was described [1]. An association of immune cell infiltration and vestibular schwannoma size has also been recently described [2] and could be a possible explanation for this finding.…”

“…A recent study by our research group demonstrated a significant association of immunohistochemical detection of COX2 and proliferative marker expression (MIB1) in a large cohort of vestibular schwannomas [ 1 ]. We have now conducted volumetric tumor measurements of preoperative tumor size and growth in this cohort to further examine the possible proliferative effect of COX2 and proliferation marker MIB1 in VS.…”

The impact of the MIB-1 index on facial nerve outcomes in vestibular schwannoma surgery

“…Paracrine cellular communication between tumour-associated macrophages and Schwann cells seems to explain the decreased anti-tumour effect of tumour-associated macrophages. Furthermore, COX2 expression was significantly associated with higher MIB-1 expression [4]. Scar formation is a known component of prolonged inflammatory reactions, which is also mediated by COX2 [42].…”

Vestibular Schwannoma: What We Know and Where We are Heading

“…In a 2019 study, tissue samples of 1048 tumours were analysed. It was discovered that while COX-2 expression increased with tumour proliferation, the use of acetylsalicylic acid did not alter COX-2 expression [85]. This study used tumour tissue retrospectively which can lend itself to selection bias since large tumours are more likely to be managed surgically.…”