Tannapfel A, Hahn H A, Katalinic A, Fietkau R J, Kühn R, Wittekind C W
Institute of Pathology, University of Leipzig, Germany.
Anticancer Res. 1997 Mar-Apr;17(2A):1155-62.
Given the growing evidence that proliferation indices may be of prognostic significance in renal cell carcinoma and that parameters of cell loss (usually, but not exclusively due to programmed cell death) are biologically relevant, identification and quantitation of apoptosis and possible regulatory factors are of considerable clinical importance.
Apoptotic cells were identified and quantified in a series of 87 curatively-resected (R0) renal cell carcinomas using the in situ end labeling method in combination with morphological criteria. The proliferative activity was determined by immunohistochemical assessment of the MIB-1 (Ki-67)-and proliferating cell nuclear antigen (PCNA). The immunoreactivity of p53 was analysed using the DO7 antibody. Immunostaining of p53 has been linked to the accumulation of mutant p53 protein. The results obtained were compared with UICC pathohistological stage and grade and finally with disease-related survival rate.
In each carcinoma examined, we could demonstrate apoptosis of varying degrees with in a range from 1 to 19 and with a median of 5. Immunostaining of p53 suggested the presence of mutant p53 in 24/87 (28%). A reciprocal correlation was found between apoptosis and p53-positivity in terms of significantly less apoptosis in p53-positive tumors. Positive statistical correlations were seen between the tumor grade and MIB-1/PCNA positivity and apoptosis. In univariate survival analysis, stage and grade, MIB-1 and PCNA index and apoptotic index were significantly related to prognosis. Multivariate Cox disease-related survival analysis revealed that stage of disease and MIB-1 were significant independent prognostic factors.
These results indicate that apoptosis and cell proliferation are strongly related in renal cell carcinoma and that the presence of mutant p53 seems to be a negative regulator of apoptosis. In univariant survival analysis, apoptosis was, in addition to other parameters, of prognostic significance. However, multivariate analysis found that only the stage of the disease and MIB-1 were independent prognostic factors.
鉴于越来越多的证据表明增殖指数可能对肾细胞癌具有预后意义，并且细胞丢失参数（通常但并非仅由于程序性细胞死亡）具有生物学相关性，因此识别和定量凋亡及可能的调节因子具有相当重要的临床意义。
采用原位末端标记法结合形态学标准，对87例根治性切除（R0）的肾细胞癌进行凋亡细胞的识别和定量。通过免疫组织化学评估MIB-1（Ki-67）和增殖细胞核抗原（PCNA）来确定增殖活性。使用DO7抗体分析p53的免疫反应性。p53的免疫染色与突变型p53蛋白的积累有关。将所得结果与国际抗癌联盟（UICC）的病理组织学分期和分级进行比较，最后与疾病相关生存率进行比较。
在每例检查的癌组织中，我们都能证明存在不同程度的凋亡（范围为1至19，中位数为5）。p53免疫染色表明24/87（28%）存在突变型p53。在p53阳性肿瘤中凋亡明显较少，发现凋亡与p53阳性之间呈负相关。肿瘤分级与MIB-1/PCNA阳性及凋亡之间存在正相关。在单因素生存分析中，分期和分级、MIB-1和PCNA指数以及凋亡指数与预后显著相关。多因素Cox疾病相关生存分析显示，疾病分期和MIB-1是显著的独立预后因素。
这些结果表明，肾细胞癌中凋亡与细胞增殖密切相关，突变型p53的存在似乎是凋亡的负调节因子。在单因素生存分析中，除其他参数外，凋亡具有预后意义。然而，多因素分析发现只有疾病分期和MIB-1是独立的预后因素。
