Michalides R J, van Veelen N M, Kristel P M, Hart A A, Loftus B M, Hilgers F J, Balm A J
Division of Tumor Biology, The Netherlands Cancer Institute, Amsterdam.
Arch Otolaryngol Head Neck Surg. 1997 May;123(5):497-502. doi: 10.1001/archotol.1997.01900050045005.
To evaluate the overexpression of cyclin D1 and p53 as a prognostic marker of squamous cell carcinoma of the head and neck and to investigate whether deregulation of these genes is associated with an unfavorable course of disease.
Retrospective study.
Formalin-fixed, paraffin-embedded tumor materials that were obtained from a well-characterized series of 115 patients with resectable head and neck cancer at The Netherlands Cancer Institute, Amsterdam, were analyzed by immunohistochemical methods using antiserum samples that were directed against 2 proteins (ie, cyclin D1 and p53), which are crucial in the regulation of the G1 phase of the cell cycle.
Overexpression of cyclin D1 protein was found in 49% of the patients with squamous cell carcinoma of the head and neck. This overexpression was not associated with known prognostic factors (eg, the T and N stages). Tumors recurred more frequently and in a shorter period in patients whose primary tumors showed an overexpression of cyclin D1 protein. This difference (P = .05) was statistically significant in a stepwise proportional hazard regression analysis. However, since a discrepancy in staining results was observed between the biopsy and resection materials that were taken from the same patient, this result may not have been applicable in the evaluation of biopsy specimens only. This discrepancy is most likely owing to tissue heterogeneity. The overexpression of p53 that was found in 42% of the patients was of no prognostic significance.
These data provide evidence that overexpression of cyclin D1 protein in resection material of squamous cell carcinomas of the head and neck is indicative of a poor prognosis, independently of other known prognostic factors. Whether overexpression of cyclin D1 may therefore be used to select patients for more intensive treatment should be examined in the context of a clinical trial.
评估细胞周期蛋白D1和p53的过表达作为头颈部鳞状细胞癌预后标志物的情况，并研究这些基因的失调是否与疾病的不良进程相关。
回顾性研究。
使用针对细胞周期G1期调控中至关重要的2种蛋白质（即细胞周期蛋白D1和p53）的抗血清样本，通过免疫组化方法分析从荷兰癌症研究所（位于阿姆斯特丹）的115例具有明确特征的可切除头颈癌患者系列中获取的福尔马林固定、石蜡包埋的肿瘤材料。
在49%的头颈部鳞状细胞癌患者中发现细胞周期蛋白D1蛋白过表达。这种过表达与已知的预后因素（如T和N分期）无关。原发性肿瘤显示细胞周期蛋白D1蛋白过表达的患者肿瘤复发更频繁且复发时间更短。在逐步比例风险回归分析中，这种差异（P = 0.05）具有统计学意义。然而，由于在取自同一患者的活检和切除材料之间观察到染色结果存在差异，该结果可能仅适用于活检标本的评估。这种差异很可能是由于组织异质性。在42%的患者中发现的p53过表达无预后意义。
这些数据表明，头颈部鳞状细胞癌切除材料中细胞周期蛋白D1蛋白的过表达预示着预后不良，独立于其他已知的预后因素。因此，细胞周期蛋白D1的过表达是否可用于选择需要更强化治疗的患者，应在临床试验的背景下进行研究。
