Niotis Athanasios, Tsiambas Evangelos, Fotiades Panagiotis P, Ragos Vasileios, Polymeneas Georgios
2nd Department of Surgery, National and Kapodistrian University of Athens, School of Medicine, Aretaieion University Hospital, Athens, Greece.
J BUON. 2018 Dec;23(7):24-27.
Aberrant cell proliferation is a major cause in the development and progression of carcinogenic process. Epithelia characterized by increased mitotic rates accumulate easily gross numerical and structural chromosomes (polysomy/aneuploidy) and specific gene (deletions, amplifications, point mutations, translocations) deregulations that lead to their progressive neoplastic and finally malignant transformation. Molecules that are critical for evaluating the proliferation status of the corresponding tissues include mainly ki-67 (cytogenetic band: 10q26.2), and also Topoisomerase IIa/Topo IIa (cytogenetic band: 17q21.2). Both of them demonstrate different expression patterns in every cell cycle phase and their estimated expression as Nuclear Labeling Index (NLI) is a very useful tool for assessing the aggressiveness of the examined pre- and malignant tissues. In fact, ki-67 expression increases as a cell progresses through the cell cycle, with highest expression being seen in G2/M phase cell, whereas Topo IIa is expressed in proliferating cells in the late S phase with a peak in G2-M phases. Concerning colon adenocarcinoma, high expression levels of them seem to correlate with advanced disease and also with modified response rates to specific chemotherapeutic agents, such as doxorubicin, an inhibitor of Topo IIa. In the current molecular review we explored the role of these proliferative markers in colon adenocarcinoma and their influence in the tumor biological behavior.
异常细胞增殖是致癌过程发展和进展的主要原因。以有丝分裂率增加为特征的上皮细胞容易积累大量的数值和结构染色体(多体性/非整倍体)以及特定基因(缺失、扩增、点突变、易位)的失调,这些失调导致其逐渐发生肿瘤性变化并最终发生恶性转化。对评估相应组织增殖状态至关重要的分子主要包括ki-67(细胞遗传学带:10q26.2),还有拓扑异构酶IIa/Topo IIa(细胞遗传学带:17q21.2)。它们在每个细胞周期阶段都表现出不同的表达模式,其作为核标记指数(NLI)的估计表达是评估所检查的癌前组织和恶性组织侵袭性的非常有用的工具。事实上,随着细胞在细胞周期中进展,ki-67表达增加,在G2/M期细胞中表达最高,而Topo IIa在S期后期的增殖细胞中表达,在G2-M期达到峰值。关于结肠腺癌,它们的高表达水平似乎与疾病进展以及对特定化疗药物(如Topo IIa抑制剂阿霉素)的反应率改变相关。在当前的分子综述中,我们探讨了这些增殖标志物在结肠腺癌中的作用及其对肿瘤生物学行为的影响。