Marioni Gino, Ottaviano Giancarlo, Marchese-Ragona Rosario, Fasanaro Elena, Tealdo Giulia, Zanotti Claudia, Randon Benedetto, Giacomelli Luciano, Stellini Edoardo, Blandamura Stella
Department of Neurosciences DNS, Otolaryngology Section, University of Padova, Padova, Italy.
Department of Radiotherapy, Veneto Institute of Oncology, IOV-IRCCS, Padova, Italy.
J Clin Pathol. 2017 Dec;70(12):1033-1037. doi: 10.1136/jclinpath-2016-204230. Epub 2017 Apr 26.
Survivin-a member of the family of inhibitor of apoptosis proteins that control cell division, apoptosis and metastasis-is overexpressed in virtually all human cancers, including laryngeal squamous cell carcinoma (LSCC). Recent findings also correlate survivin expression with the regulation of angiogenesis. The novel main aim of this study was a preliminary investigation into the potential role of survivin expression in LSCC neoangiogenesis, as determined by endoglin-assessed microvascular density (MVD).
Immunohistochemical expression of nuclear survivin and endoglin-assessed MVD were ascertained by image analysis in 75 consecutive LSCCs.
Statistical analysis disclosed a strong direct correlation between nuclear survivin expression and MVD. Patients whose nuclear survivin expression was ≥6.0% had a significantly higher LSCC recurrence rate, and a significantly shorter disease-free survival (DFS) than those with a nuclear survivin expression <6.0%. The LSCC recurrence rate was also higher and the DFS shorter in patients with endoglin-assessed MVD ≥6.89%. The OR for recurrence was 2.79 in patients with LSCC with a nuclear survivin expression ≥6.0%, and 12.31 in those with an MVD≥6.89%.
Survivin-targeting strategies to enhance tumour cell response to apoptosis and inhibit tumour growth should receive more attention with a view to developing agents for use in multimodality advanced LSCC treatment, or combined with conventional chemotherapy. Given the present preliminary evidence in LSCC, survivin targeting should also be further investigated for anti-angiogenic purposes, to reduce tumour blood flow and induce cancer necrosis.
生存素是凋亡抑制蛋白家族的成员，可控制细胞分裂、凋亡和转移，几乎在所有人类癌症中均有过表达，包括喉鳞状细胞癌（LSCC）。最近的研究结果还表明生存素表达与血管生成的调节有关。本研究的新主要目的是初步调查生存素表达在LSCC新生血管生成中的潜在作用，通过内皮糖蛋白评估微血管密度（MVD）来确定。
通过图像分析确定75例连续LSCC中核生存素的免疫组化表达和内皮糖蛋白评估的MVD。
统计分析显示核生存素表达与MVD之间存在强烈的直接相关性。核生存素表达≥6.0%的患者LSCC复发率显著更高，无病生存期（DFS）显著短于核生存素表达<6.0%的患者。内皮糖蛋白评估的MVD≥6.89%的患者LSCC复发率也更高，DFS更短。LSCC核生存素表达≥6.0%的患者复发的OR为2.79，MVD≥6.89%的患者为12.31。
旨在增强肿瘤细胞对凋亡的反应并抑制肿瘤生长的靶向生存素策略应受到更多关注，以期开发用于多模式晚期LSCC治疗的药物，或与传统化疗联合使用。鉴于目前LSCC的初步证据，靶向生存素也应进一步研究其抗血管生成作用，以减少肿瘤血流并诱导癌症坏死。
