Merola Elettra, Mattioli Eliseo, Minimo Corrado, Zuo Weineng, Rabitti Carla, Cicala Michele, Caviglia Renato, Pollice Lucio, Gabbrielli Armando, Giordano Antonio, Claudio Pier Paolo
Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, Temple University, Philadelphia, Pennsylvania 19122-6099, USA.
J Cell Physiol. 2006 May;207(2):512-9. doi: 10.1002/jcp.20590.
Control of the G1/S-phase transition as well as angiogenic switch are two of the most studied mechanisms in cancer. The current study examined the correlation between the immunohistochemical expression of pRb2/p130, VEGF, EZH2, p53, p16, p21waf-1, p27, and PCNA in Barrett's esophagus (BE). Overall, p53 showed a much higher expression in BE patients (up to 50%) than in controls (1-10%) (P < 0.005). Also p21 showed a downregulation in BE when compared to normal esophagus (70% of cells vs. 65%), but the difference did not show any statistical significance (P = 0.45). pRb2/p130 was detected in 80% of cells in normal controls, but showed positive in only 20% of cells in BE biopsies. Additionally, Rb2/p130 expression was inversely correlated to that of VEGF, EZH2, and PCNA (P < 0.0001, P = 0.0032, P < 0.001, respectively). p27 stained more intensely and in a widespread manner (70%) cells in normal esophageal tissues but about only 30% in BE samples (P < 0.001). Lastly, in accordance with other reports, we also found p16 expressed by immunohistochemistry at high levels in normal controls and at low levels in BE (P < 0.001). In conclusion, p16, p21, p27, and p53 staining confirmed previously published data. Interestingly, pRb2/p130 expression was found significantly decreased in metaplastic epithelium compared to normal controls and showed significant inverse correlation with the expression of other markers, such as VEGF, EZH2, and PCNA. These data, taken together, indicate that these molecular events occurring in Barrett's metaplasia (BM) may represent one of the many steps taking place during esophageal malignant progression such as impairment of cell-cycle control, altered differentiation, and unbalanced angiogenesis.
G1/S期转换的调控以及血管生成开关是癌症研究最多的两种机制。本研究检测了巴雷特食管（BE）中pRb2/p130、VEGF、EZH2、p53、p16、p21waf-1、p27和PCNA免疫组化表达之间的相关性。总体而言，p53在BE患者中的表达（高达50%）远高于对照组（1%-10%）（P<0.005）。与正常食管相比，p21在BE中也呈下调（70%的细胞对65%），但差异无统计学意义（P=0.45）。在正常对照组80%的细胞中检测到pRb2/p130，但在BE活检组织中仅20%的细胞呈阳性。此外，Rb2/p130的表达与VEGF、EZH2和PCNA的表达呈负相关（分别为P<0.0001、P=0.0032、P<0.001）。p27在正常食管组织中染色更强烈且广泛（70%的细胞），但在BE样本中约仅30%（P<0.001）。最后，与其他报道一致，我们还发现免疫组化检测到p16在正常对照组中高水平表达，在BE中低水平表达（P<0.001）。总之，p16、p21、p27和p53染色证实了先前发表的数据。有趣的是，与正常对照组相比，化生上皮中pRb2/p130表达显著降低，且与其他标志物如VEGF、EZH2和PCNA的表达呈显著负相关。综上所述，这些发生在巴雷特化生（BM）中的分子事件可能代表了食管恶性进展过程中发生的众多步骤之一，如细胞周期控制受损、分化改变和血管生成失衡。
