Ioachim E, Peschos D, Goussia A, Mittari E, Charalabopoulos K, Michael M, Salmas M, Vougiouklakis Th, Assimakopoulos D, Agnantis N J
Department of Pathology, Medical School, University of Ioannina, Ioannina, Greece.
J Exp Clin Cancer Res. 2004 Jun;23(2):277-83.
The expression of cell-cycle progression molecules cyclin D1 and cyclin E were immunohistochemically examined in a series of 64 squamous cell invasive carcinomas of the larynx, 10 in situ carcinomas, 34 cases of dysplasia, 11 papillomas and 23 cases of keratosis. The results of their expression were compared with two cell-cycle implicated tumor suppressor proteins p53 and pRb as well as with two proliferation associated indices PCNA and Ki-67 in an attempt to elucidate their potential role in the pathogenesis and progression of these lesions. Nuclear staining for cyclin D1 and E (>5% positive cells) was observed in 19% and 39.7% of the laryngeal carcinomas, respectively. Significantly elevated levels of cyclin D1 and E in invasive laryngeal carcinomas compared with in situ carcinomas were revealed (p=0.045 and p=0.0003, respectively). High levels of cyclin D1 and E expression were correlated with increased Ki-67 score (p=0.037 and 0.017 respectively). A significant positive correlation between cyclin D1 and E was also detected in carcinomas (p=0.018). Decreased levels of cyclins D1 and E in the group of in situ carcinomas compared with those of dysplastic cases and papillomas were also observed. In the dysplastic lesions cyclin D1 expression was correlated with pRb expression (p=0.02). In the cases of keratosis cyclins D1 and E expression were correlated with pRb (p=0.002 and p=0.036, respectively), while cyclin D1 was associated with PCNA (p=0.008) and Ki-67 score (p=0.009). The prognostic significance of cyclins D1, E in determining the risk of recurrence and overall survival with both univariate (long-rang test) and multivariate (Cox regression) methods of analysis showed no statistically significant differences. We conclude that the expression of cyclins D1 and E in squamous cell carcinomas of the larynx does not seem to have a prognostic significance. In addition, their expression may be involved in the development of laryngeal lesions, implicated in cell proliferation, with other cell cycle related proteins, probably by different molecular pathways.
采用免疫组织化学方法检测了64例喉鳞状细胞浸润癌、10例原位癌、34例发育异常、11例乳头状瘤和23例角化病中细胞周期进展分子细胞周期蛋白D1和细胞周期蛋白E的表达。将它们的表达结果与两种与细胞周期相关的肿瘤抑制蛋白p53和pRb以及两种增殖相关指标PCNA和Ki-67进行比较,以试图阐明它们在这些病变的发病机制和进展中的潜在作用。在喉癌中,分别有19%和39.7%观察到细胞周期蛋白D1和E的核染色(阳性细胞>5%)。与原位癌相比,浸润性喉癌中细胞周期蛋白D1和E的水平显著升高(分别为p=0.045和p=0.0003)。细胞周期蛋白D1和E的高表达与Ki-67评分增加相关(分别为p=0.037和0.017)。在癌中还检测到细胞周期蛋白D1和E之间存在显著正相关(p=0.018)。与发育异常病例和乳头状瘤相比,原位癌组中细胞周期蛋白D1和E的水平也降低。在发育异常病变中,细胞周期蛋白D1的表达与pRb表达相关(p=0.02)。在角化病病例中,细胞周期蛋白D1和E的表达与pRb相关(分别为p=0.002和p=0.036),而细胞周期蛋白D1与PCNA相关(p=0.008)和Ki-67评分相关(p=0.009)。采用单因素(长期试验)和多因素(Cox回归)分析方法,细胞周期蛋白D1、E在确定复发风险和总生存期方面的预后意义均无统计学显著差异。我们得出结论,喉鳞状细胞癌中细胞周期蛋白D1和E的表达似乎没有预后意义。此外,它们的表达可能参与喉病变的发展,与其他细胞周期相关蛋白一起参与细胞增殖,可能通过不同的分子途径。