Department of Pathology and Cytology, School of Medicine, Duzce University, Konuralp Campus, Duzce, Turkey.
Department of Pathology, School of Medicine, Bursa Uludag University, Gorukle Campus, Bursa, Turkey.
J Environ Pathol Toxicol Oncol. 2022;41(1):45-53. doi: 10.1615/JEnvironPatholToxicolOncol.2021039719.
Malignant peripheral nerve sheath tumors (MPNSTs), glioblastomas (GBMs), and malignant melanomas (MMs) are neural crest-originating aggressive tumors with a poor prognosis. Signal transducer and transcription activator 3 (STAT3) plays a role in many biological processes, including cell life and proliferation, the acute phase response, chronic inflammation, autoimmunity, metabolism, and cancer progression, It is also known to be a prooncogenic transcription factor. Vascular endothelial growth factor (VEGF) is one of the most potent proangiogenic stimuli ever identified. It mediates tumor neovascularization, and is associated with angiogenesis and lymphangiogenesis. The prostate-specific membrane antigen (PSMA) folate hydrolase I, despite its name, has been found in tissues other than the prostate. It is overexpressed in prostate cancer cells and several other cancers, and has the potential to be a target for radioligand therapy. We investigated the value of STAT3, VEGF and PSMA immunohistochemical expression patterns and their effects on survival in MPNSTs, GBMs, and MMs. Their expression patterns were evaluated in 25 MPNSTs, 27 GBMs, and 25 MM cases. All GBM cases stained positively for STAT3 and VEGF. In the other groups, the staining patterns were heterogeneous. None of the cases showed positive staining with PSMA. There was no statistically significant difference in survival between cases with differing VEGF and STAT3 staining patterns in the MPSNT and MM groups, but there was an increase in mortality as the VEGF score increased in the GBM group. The suppression of VEGF and STAT3 may be a promising avenue for treatment of MPNSTs, GBMs, and MMs, although further research is needed.
恶性外周神经鞘瘤(MPNST)、胶质母细胞瘤(GBM)和恶性黑色素瘤(MM)是起源于神经嵴的侵袭性肿瘤,预后较差。信号转导和转录激活因子 3(STAT3)在许多生物学过程中发挥作用,包括细胞生命和增殖、急性期反应、慢性炎症、自身免疫、代谢和癌症进展,它也被认为是一种致癌转录因子。血管内皮生长因子(VEGF)是迄今为止发现的最有效的促血管生成刺激物之一。它介导肿瘤新生血管形成,并与血管生成和淋巴管生成有关。前列腺特异性膜抗原(PSMA)叶酸水解酶 I,尽管它的名字,已在前列腺以外的组织中发现。它在前列腺癌细胞和其他几种癌症中过度表达,有可能成为放射性配体治疗的靶点。我们研究了 STAT3、VEGF 和 PSMA 免疫组织化学表达模式及其对 MPNST、GBM 和 MM 生存的影响。在 25 例 MPNST、27 例 GBM 和 25 例 MM 病例中评估了它们的表达模式。所有 GBM 病例均对 STAT3 和 VEGF 染色呈阳性。在其他组中,染色模式存在异质性。没有一个病例对 PSMA 表现出阳性染色。在 MPSNT 和 MM 组中,VEGF 和 STAT3 染色模式不同的病例之间的生存率没有统计学差异,但在 GBM 组中,VEGF 评分增加时死亡率增加。抑制 VEGF 和 STAT3 可能是治疗 MPNST、GBM 和 MM 的有前途的途径,尽管需要进一步研究。