First Department of Otorhinolaryngology, Head and Neck Surgery, Hippocration Hospital, University of Athens, Athens, Greece.
Department of Immunohistochemistry and Molecular Biology, 401 General Army Hospital, Athens, Greece
Anticancer Res. 2019 Aug;39(8):4137-4142. doi: 10.21873/anticanres.13572.
P53 is a key regulator of genomic stability and function, acting as a tumor suppressor protein. Our aim was to correlate P53 expression with murine double minute 2 (MDM2), a proto-oncogene that interacts with P53 and forms an auto-regulatory pathway, in laryngeal squamous cell carcinoma (LSCC).
A total of 50 LSCC cases were included in the study. Immunohistochemistry was applied by using antibodies to P53 and MDM2 in the corresponding tissue sections. Protein expression levels for both molecules were measured by implementing a digital image analysis assay (immunostaining intensity levels, densitometric evaluation).
Overexpression of P53 protein was observed in 16/50 (32%) LSCC cases, while 22/50 (44%) cases strongly expressed MDM2 protein. Interestingly, in 13/50 (26%) cases, combined overexpression of P53/MDM2 was detected. Overall P53 was strongly positively correlated with MDM2 expression (p=0.001). Both P53 and MDM2 overexpression were significantly correlated with advanced stage of LSCC (p=0.032 and p=0.001, respectively). Additionally, MDM2 was found to be associated with poorer survival of patients (p=0.046).
Aberrant co-expression of P53 and MDM2 is associated with advanced stage in LSCC. Furthermore, MDM2 overexpression is a frequent and critical genetic event in LSCC and seems to negatively affect survival.
P53 是基因组稳定性和功能的关键调节因子,作为一种肿瘤抑制蛋白发挥作用。我们的目的是在喉鳞状细胞癌(LSCC)中,将 P53 表达与鼠双微体 2(MDM2)相关联,MDM2 是一种原癌基因,与 P53 相互作用并形成自动调节途径。
共有 50 例 LSCC 病例纳入研究。使用针对 P53 和 MDM2 的抗体在相应的组织切片中进行免疫组织化学染色。通过实施数字图像分析测定法(免疫染色强度水平,密度测定评估)来测量两种分子的蛋白表达水平。
在 50 例 LSCC 病例中,观察到 P53 蛋白过表达 16/50(32%),而 22/50(44%)病例强烈表达 MDM2 蛋白。有趣的是,在 13/50(26%)病例中,检测到 P53/MDM2 的联合过表达。总体而言,P53 与 MDM2 表达呈强烈正相关(p=0.001)。P53 和 MDM2 的过表达均与 LSCC 的晚期阶段显著相关(p=0.032 和 p=0.001)。此外,发现 MDM2 与患者的生存率降低相关(p=0.046)。
P53 和 MDM2 的异常共表达与 LSCC 的晚期阶段相关。此外,MDM2 的过表达是 LSCC 中常见且关键的遗传事件,似乎对生存产生负面影响。