Tsiambas E, Karameris A, Gourgiotis S, Salemis N, Athanassiou A E, Karakitsos P, Papalois A, Merikas E, Kosmidis P, Patsouris E
Department of Immunohistochemistry and Molecular Cytopathology, 401 General Army Hospital, Athens, Greece.
J BUON. 2007 Apr-Jun;12(2):261-7.
Deregulation of cell cycle control molecules, such as cyclins and their inhibitors, is a crucial event in the carcinogenetic process. Our aim was to identify potential correlations between p16 and cyclin D1 expression in pancreatic ductal adenocarcinoma (PDAC) that affect the biological behavior of this neoplasm.
Using tissue microarray (TMA) technology, 50 paraffin-embedded tissue samples of histologically confirmed primary PDACs were cored twice and re-embedded to the final recipient block. Immunohistochemistry (IHC) was performed using monoclonal anti-p16 and anti-cyclin D1 antibodies. Protein expression levels were determined by performing computerized image analysis (CIA; estimation of Nuclear Labeling Index-NLI). SPSS (chi square test and interrater Cohen's kappa) was used for statistical analysis.
Cyclin D1 overexpression was observed in 24/50 (48%) of the examined carcinomas, whereas p16 loss or reduced expression was detected in 40/50 (80%) cases. Statistical significance was noted when correlating grade to cyclin D1 (p=0.038), stage to p16 (p=0.012) and also to cyclin D1 (p=0.011). Interestingly, combined protein alterations (p16 loss and cyclin D1 overexpression) were observed in 23/50 (46%) cases associated with advanced stage (p=0.019). Overall combined expression of the two molecules demonstrated a significantly low value (kappa=0.012; 95% confidence interval-CI: 0.010-0.014).
A significant proportion of PDACs is characterized by simultaneous protein alterations regarding p16 and cyclin D1 genes. This mechanism of genetic deregulation in cell cycle potentially explains in part the aggressive phenotype of this neoplasm.
细胞周期调控分子（如细胞周期蛋白及其抑制剂）的失调是致癌过程中的关键事件。我们的目的是确定胰腺导管腺癌（PDAC）中p16与细胞周期蛋白D1表达之间的潜在相关性，这些相关性会影响该肿瘤的生物学行为。
使用组织微阵列（TMA）技术，对50例经组织学证实的原发性PDAC石蜡包埋组织样本进行两次取芯，并重新包埋到最终的受体块中。使用单克隆抗p16和抗细胞周期蛋白D1抗体进行免疫组织化学（IHC）。通过计算机图像分析（CIA；核标记指数-NLI估计）确定蛋白质表达水平。使用SPSS（卡方检验和评价者间科恩kappa系数）进行统计分析。
在24/50（48%）的检查癌组织中观察到细胞周期蛋白D1过表达，而在40/50（80%）的病例中检测到p16缺失或表达降低。在将分级与细胞周期蛋白D1相关联（p = 0.038）、分期与p16相关联（p = 0.012）以及分期与细胞周期蛋白D1相关联（p = 0.011）时，发现具有统计学意义。有趣的是，在23/50（46%）与晚期相关的病例中观察到联合蛋白改变（p16缺失和细胞周期蛋白D1过表达）（p = 0.019）。这两种分子的总体联合表达显示出显著低值（kappa = 0.012；95%置信区间-CI：0.010 - 0.014）。
相当一部分PDAC的特征是p16和细胞周期蛋白D1基因同时发生蛋白质改变。这种细胞周期遗传失调机制可能部分解释了该肿瘤的侵袭性表型。
