Analysis of Ki-67 antigen expression, DNA proliferative fraction, and survival in resected cancer of the pancreas
Analysis of Ki-67 antigen expression, DNA proliferative fraction, and survival in resected cancer of the pancreas
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DOI：
10.1016/j.amjsurg.2003.07.002
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发表时间：
2003-11-01
影响因子：
3
通讯作者：
Wiebke, EA
中科院分区：
文献类型：
--
作者：
Stanton, KJ;Sidner, RA;Wiebke, EA
背景：癌胚抗原、CA19-9、倍体分析和流式细胞术S分期等预后标志物对胰腺癌预后的预测作用并不一致。我们选择MIB-1单抗和数字图像分析作为胰腺癌的预后指标，并与DNA倍体分析和S时相分析进行比较。MIB-1确定Ki67抗原存在于除胰腺癌外的所有细胞周期的细胞核中。方法：我们回顾了1989~1994年间手术切除的33例胰腺癌患者的临床资料。切片行MIB-1染色，定量图像分析测定阳性核数，以MIB-1标记指数(LI)表示。结果：胰腺癌MIB-1LI在癌内和癌间具有异质性。肿瘤的MIB-1LI为28+/-15(中位数29)。生存与MIB-1表达无相关性(R2=0.03)。同样，MIB-1LI与S期细胞百分率、G(2)/M期细胞百分率、增殖细胞总数(S+G(2)/M期；R2=0.0 1)无相关性，与倍性也无相关性(P=0.88)。结论：在本组患者中，胰腺癌中由Ki6 7核抗原表达决定的核增殖与生存期无关，也不是一个有用的预后指标。尽管直觉上有相反的想法，但通过流式细胞仪确定的细胞周期分析与胰腺癌Ki67表达之间没有相关性。目前评估胰腺癌根治性切除后预后的方法，包括淋巴结和切缘状况、肿瘤大小，以及可能通过流式细胞术确定的DNA倍体，都没有通过使用MIB-1单抗进行图像分析来评估核增殖情况而得到加强。(C)2003 Excerpta Medica，Inc.保留所有权利。
Background: Prognostic markers for pancreas cancer, such as CEA, CA19-9, ploidy analysis, and S-phase determination using flow cytometry, have not been consistently predictive. We chose to evaluate nuclear proliferation, as measured by the MIB-1 monoclonal antibody and digital image analysis, as a prognostic marker in pancreatic carcinoma, and compare the findings with DNA ploidy and S-phase analysis. MIB-1 identifies the Ki67 antigen present in nuclei of cells in all phases of the cell cycle except GO.Methods: We retrospectively reviewed 33 patients with pancreatic adenocarcinoma resected for cure between 1989 and 1994 with available fixed tissue. Sectioned tissue was stained with MIB-1, and the number of positively stained nuclei determined and expressed as a MIB-1 labeling index (LI) by quantitative image analysis. Disaggregated nuclei were analyzed by flow cytometry using standard techniques.Results: MIB-1 LI for pancreas cancers was heterogeneous within and between cancers. The MIB-1 LI for the cancers was 28 +/- 15 (median 29). There was no correlation between survival and MIB-1 expression (R-2 = 0.03). Likewise, there was no correlation between MIB-1 LI and percentage of cells in S-phase, G(2)/M, or total proliferating cells (S+G(2)/M; R-2 = 0.01), nor was there a difference between MIB-1 LI and ploidy (P = 0.88).Conclusions: We conclude that in our patient population, nuclear proliferation in pancreatic cancer, as determined by expression of Ki67 nuclear antigen, does not appear to correlate with survival and is not a useful prognostic marker. Despite intuitive thoughts to the contrary, there is no correlation between cell cycle analysis as determined by flow cytometry and Ki67 expression in pancreas cancer. Current methods of assessing prognosis after curative resection of cancer of the pancreas, including lymph node and margin status, tumor size, and possibly DNA ploidy as determined by flow cytometry, are not augmented by the assessment of nuclear proliferation by image analysis using the MIB-1 monoclonal antibody. (C) 2003 Excerpta Medica, Inc. All rights reserved.