Jovanovic Ivan P, Radosavljevic Gordana D, Simovic-Markovic Bojana J, Stojanovic Stevan P, Stefanovic Srdjan M, Pejnovic Nada N, Arsenijevic Nebojsa N
1Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Serbia.
J BUON. 2014 Oct-Dec;19(4):944-52.
Laryngeal squamous cell carcinoma (LSCC) represents one of the most common cancers of the head and neck and the search for molecular markers is required for early diagnosis, prognosis and optimal therapy. The purpose of this study was to investigate the clinical significance of Cyclin D1, FGF3, p16 and p21 protein expression in LSCC and laryngeal dysplasia (LD) and to evaluate the associations between their expression levels and clinicopathological parameters of patients with LSCC.
Immunohistochemistry was employed to detect and quantify the expression levels of Cyclin D1, FGF3, p16 and p21 in the laryngeal tissues of 48 LSCC patients, 32 patients with LD and 28 subjects with healthy laryngeal mucosa (HLM).
Significantly higher percentage of LSCC patients had positive Cyclin D1 expression compared with LD patients and HLM subjects (both p<0.01) and positive FGF3 expression than HLM subjects (p<0.05), while no differences in p16 and p21 positive expression were found among studied groups. The levels of Cyclin D1, FGF3 and p16 expression, as evaluated by immunostaining score, were significantly higher in patients with LSCC compared with LD and HLM groups (all p<0.05). Cyclin D1 proved to be highly sensitive and specific marker in differentiating LSCC from LD (sensitivity 81.2%, specificity 83.9%), while high sensitivity (81.2%) and lower specificity (41.4%) was observed in differentiating from HLM. Cyclin D1 and p21 expression levels were associated with regional lymph node metastases (both p<0.05) and Cyclin D1 expression levels significantly correlated with LSCC lymphatic invasion (x(2)=8.862; df=3; ?=0.031).
Cyclin D1, FGF3 and p16 are overexpressed in patients with LSCC. Cyclin D1 is a highly sensitive marker in differentiating LSCC from LD or HLM. Cyclin D1 and p21 expression levels may be useful as predictive markers of metastases in LSCC.
喉鳞状细胞癌（LSCC）是头颈部最常见的癌症之一，需要寻找分子标志物用于早期诊断、预后评估和优化治疗。本研究旨在探讨细胞周期蛋白D1（Cyclin D1）、成纤维细胞生长因子3（FGF3）、p16和p21蛋白表达在LSCC和喉发育异常（LD）中的临床意义，并评估其表达水平与LSCC患者临床病理参数之间的相关性。
采用免疫组织化学法检测和定量48例LSCC患者、32例LD患者和28例健康喉黏膜（HLM）受试者喉组织中Cyclin D1、FGF3、p16和p21的表达水平。
与LD患者和HLM受试者相比，LSCC患者中Cyclin D1表达阳性的比例显著更高（均p<0.01），FGF3表达阳性的比例高于HLM受试者（p<0.05），而研究组之间p16和p21阳性表达无差异。通过免疫染色评分评估，LSCC患者中Cyclin D1、FGF3和p16的表达水平显著高于LD组和HLM组（均p<0.05）。Cyclin D1被证明是区分LSCC与LD的高度敏感和特异的标志物（敏感性81.2%，特异性83.9%），而在区分与HLM时观察到高敏感性（81.2%）和较低的特异性（41.4%）。Cyclin D1和p21表达水平与区域淋巴结转移相关（均p<0.05），且Cyclin D1表达水平与LSCC淋巴浸润显著相关（x(2)=8.862；自由度=3；P=0.031）。
Cyclin D1、FGF3和p16在LSCC患者中过度表达。Cyclin D1是区分LSCC与LD或HLM的高度敏感标志物。Cyclin D1和p21表达水平可能作为LSCC转移的预测标志物。
