Ciesielska Urszula, Zatonski Tomasz, Nowinska Katarzyna, Ratajczak-Wielgomas Katarzyna, Grzegrzolka Jedrzej, Piotrowska Aleksandra, Olbromski Mateusz, Pula Bartosz, Podhorska-Okolow Marzenna, Dziegiel Piotr
Department of Histology and Embryology, Wroclaw Medical University, Wroclaw, Poland
Department of Otolaryngology, Head and Neck Surgery, Wroclaw Medical University, Wroclaw, Poland.
Anticancer Res. 2017 May;37(5):2407-2415. doi: 10.21873/anticanres.11580.
The deregulation of the cell cycle is crucial for the processes of carcinogenesis and tumor progression. The cell cycle is under the control of cyclin-dependent kinases (CDKs) and their inhibitors (CDKIs). Proteins p16 and p27 are CDKIs, and their altered expression has been noticed in many types of cancers. The aim of this study has been to compare the expression levels of these proteins in laryngeal papillomas and carcinomas in order to confirm their predictive value in cancer development.
Eighty-three cases of laryngeal lesions were analyzed: cancers (51) and papillomas (32). Immunohistochemical (IHC) reactions were performed in order to detect the expression levels of p16, p27 and Ki-67. Immunofluorescence (IF) and western blot were performed on HEp-2 cell line.
The expression of p16 and p27 was decreased in cancer cells in comparison to papillomas. Additionally, we observed cytoplasmic expression of p16 in cancers and lack of such expression in papillomas. The same pattern of expression of p16 was also detected by IF and western blot analysis in HEp-2 cell line. The expression of Ki-67 protein revealed no significant differences in the case of papilloma compared with cancer, however a significant correlation between tumor grade and the nuclear expression of Ki-67 was observed.
There is a necessity in finding biomarkers, which would predict the risk level of malignant transformation. Our study has confirmed that altered expressions of the p16 and p27 proteins might be useful biomarkers in the progression of laryngeal squamous cell carcinomas (LSCC).
细胞周期失调对于致癌作用和肿瘤进展过程至关重要。细胞周期受细胞周期蛋白依赖性激酶（CDK）及其抑制剂（CDKI）的控制。蛋白质p16和p27是CDKI，它们的表达改变已在多种癌症中被注意到。本研究的目的是比较这些蛋白质在喉乳头状瘤和癌中的表达水平，以确认它们在癌症发展中的预测价值。
分析了83例喉部病变病例：癌症（51例）和乳头状瘤（32例）。进行免疫组织化学（IHC）反应以检测p16、p27和Ki-67的表达水平。在HEp-2细胞系上进行免疫荧光（IF）和蛋白质印迹分析。
与乳头状瘤相比，癌细胞中p16和p27的表达降低。此外，我们观察到p16在癌症中有细胞质表达，而在乳头状瘤中没有这种表达。在HEp-2细胞系中通过IF和蛋白质印迹分析也检测到了相同的p16表达模式。与癌症相比，乳头状瘤中Ki-67蛋白的表达没有显著差异，然而观察到肿瘤分级与Ki-67的核表达之间存在显著相关性。
有必要寻找能够预测恶性转化风险水平的生物标志物。我们的研究证实，p16和p27蛋白表达的改变可能是喉鳞状细胞癌（LSCC）进展中的有用生物标志物。
