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p53和bcl-2免疫反应性对早期浸润性pT1/pT2胃癌的预后相关性:有限胃切除术的指标?

Prognostic relevance of p53 and bcl-2 immunoreactivity for early invasive pT1/pT2 gastric carcinomas: indicators for limited gastric resections?

作者信息

Kopp R, Diebold J, Dreier I, Cramer C, Glas J, Baretton G, Jauch K W

机构信息

Department of Surgery, Klinikum Grosshadern, University of Munich, Marchioninistrasse 15, D-81377 Munich, Germany.

出版信息

Surg Endosc. 2005 Nov;19(11):1507-12. doi: 10.1007/s00464-005-0043-7. Epub 2005 Sep 21.

Abstract

BACKGROUND

Laparoscopic or endoscopic limited resection is intended to be an additional therapeutic option for the treatment of early gastric cancer. However, tumorbiologic markers to predict the outcome for patients after limited resections are missing. This study therefore investigated the prognostic relevance of p53 and bcl-2 immunoreactivity as well as the percentage of apoptotic tumor cells in early invasive pT1/pT2 tumors managed with standard operations for gastric adenocarcinoma.

METHODS

Histologic slides of 65 pT1/pT2 gastric carcinomas were investigated for bcl-2 and p53 immunoreactivity. For 35 patients, DNA fragmentation of tumor cell nuclei was determined by the terminal uridine 5'-triphosphate (UTP) nick end-labeling (TUNEL) method. Follow-up evaluation of the patients was prospectively documented for 53.4 +/- 4.1 months.

RESULTS

Findings showed that bcl-2 immunoreactivity was associated with tumors of the intestinal type according to Lauren s classification (p = 0.042), and that p53 immunoreactivity was increased in more invasive tumors (pT1 vs pT2 tumors; p = 0.047). Mean survival time was significantly longer for patients with bcl-2-negative tumors (74.3 +/- 6.8 months) than for patients with bcl-2-positive tumors (50.8 +/- 7.6 months; p = 0.024). The percentage of apoptotic tumor cell nuclei did not have prognostic relevance in the population studied and was not associated with several histopathologic parameters or bcl-2 and p53 immunoreactivity. Subgroup analysis indicated that the survival of patients with differentiated G2 and bcl-2-negative/p53-negative tumors was significantly longer (82 +/- 6 months) than the survival of patients with G2 bcl-2- and/or p53-positive tumors (41.8 +/- 12.5 months; p = 0.005), with independent prognostic relevance determined by multivariate analysis (p = 0.024).

CONCLUSION

The data reported indicate that the analysis of bcl-2 and p53 immunoreactivity seems to have prognostic implications for early invasive (pT1/pT2) gastric adenocarcinomas and may subclassify patients for minimally invasive laparoscopic or endoscopic gastric resections.

摘要

背景

腹腔镜或内镜下局限性切除术旨在成为早期胃癌治疗的一种额外治疗选择。然而,目前缺乏预测局限性切除术后患者预后的肿瘤生物学标志物。因此,本研究调查了p53和bcl-2免疫反应性以及凋亡肿瘤细胞百分比在接受标准手术治疗的早期浸润性pT1/pT2胃癌中的预后相关性。

方法

对65例pT1/pT2胃癌的组织学切片进行bcl-2和p53免疫反应性检测。对35例患者,采用末端脱氧尿苷三磷酸(UTP)缺口末端标记(TUNEL)法测定肿瘤细胞核的DNA片段化。对患者进行前瞻性随访记录,随访时间为53.4±4.1个月。

结果

结果显示,根据劳伦分类法,bcl-2免疫反应性与肠型肿瘤相关(p = 0.042),且在浸润性更强的肿瘤(pT1与pT2肿瘤;p = 0.047)中p53免疫反应性增加。bcl-2阴性肿瘤患者的平均生存时间(74.3±6.8个月)显著长于bcl-2阳性肿瘤患者(50.8±7.6个月;p = 0.024)。在本研究人群中,凋亡肿瘤细胞核百分比无预后相关性,且与多个组织病理学参数或bcl-2和p53免疫反应性无关。亚组分析表明,分化型G2且bcl-2阴性/p53阴性肿瘤患者的生存期(82±6个月)显著长于G2 bcl-2和/或p53阳性肿瘤患者(41.8±12.5个月;p = 0.005),多因素分析确定其具有独立的预后相关性(p = 0.024)。

结论

所报道的数据表明,bcl-2和p53免疫反应性分析似乎对早期浸润性(pT1/pT2)胃腺癌具有预后意义,并且可能对微创腹腔镜或内镜下胃切除术患者进行亚分类。

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