Korkolopoulou P A, Konstantinidou A E, Patsouris E S, Christodoulou P N, Thomas-Tsagli E A, Davaris P S
Department of Pathology, National and Kapodistrian University of Athens, Athens 115 27, Greece.
J Pathol. 2001 Mar;193(3):377-82. doi: 10.1002/1096-9896(2000)9999:9999<::AID-PATH812>3.0.CO;2-W.
Precise quantitation of apoptotic cells in gliomas is necessary to determine the role of apoptosis in tumour growth, prognosis, and treatment. This study investigated the incidence of baseline apoptosis in relation to proliferation status, p53 expression, standard clinicopathological parameters, and outcome, in a series of 61 patients with diffuse cerebral astrocytomas. Apoptotic fractions were quantified immunohistochemically by means of a novel monoclonal antibody recognizing exposed single-stranded (ss) regions in the DNA of apoptotic cells during heating. Proliferative activity was expressed as the percentage of Ki-67-positive cells. Tissues consisted of primary formalin-fixed, paraffin-embedded astrocytoma specimens. The apoptotic index (AI) increased with grade, proliferative activity, and p53 expression. Increased AI tended to be accompanied by a shortened overall and disease-free survival in univariate analysis in glioblastoma multiforme and astrocytoma/anaplastic astrocytoma, respectively. Multivariate analysis demonstrated that increased AI was an independent predictor of adverse significance in overall and disease-free survival. These results implicate apoptotic rate in astrocytoma aggressiveness and show that the assessment of apoptotic potential by means of anti-ssDNA monoclonal antibody provides valuable prognostic information independently of standard parameters or tumour proliferation status.
精确量化胶质瘤中的凋亡细胞对于确定凋亡在肿瘤生长、预后及治疗中的作用至关重要。本研究调查了61例弥漫性脑星形细胞瘤患者的基线凋亡发生率与增殖状态、p53表达、标准临床病理参数及预后的关系。通过一种新型单克隆抗体对凋亡分数进行免疫组化定量，该抗体可识别加热过程中凋亡细胞DNA中暴露的单链（ss）区域。增殖活性以Ki-67阳性细胞的百分比表示。组织由原发性福尔马林固定、石蜡包埋的星形细胞瘤标本组成。凋亡指数（AI）随肿瘤分级、增殖活性及p53表达的增加而升高。在多形性胶质母细胞瘤和星形细胞瘤/间变性星形细胞瘤的单因素分析中，AI升高分别倾向于伴有总生存期和无病生存期缩短。多因素分析表明，AI升高是总生存期和无病生存期不良预后的独立预测因素。这些结果表明凋亡率与星形细胞瘤的侵袭性有关，并且通过抗ssDNA单克隆抗体评估凋亡潜能可独立于标准参数或肿瘤增殖状态提供有价值的预后信息。
