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DNA倍体和c-erbB-2癌蛋白过表达在巴雷特食管腺癌中的预后价值。

Prognostic value of DNA ploidy and c-erbB-2 oncoprotein overexpression in adenocarcinoma of Barrett's esophagus.

作者信息

Nakamura T, Nekarda H, Hoelscher A H, Bollschweiler E, Harbeck N, Becker K, Siewert J R, Harbec N [corrected to Harbeck N ]

机构信息

Department of Surgery, Klinikum rechts der Isar, Technical University of Munich, Germany.

出版信息

Cancer. 1994 Apr 1;73(7):1785-94. doi: 10.1002/1097-0142(19940401)73:7<1785::aid-cncr2820730703>3.0.co;2-0.

DOI:10.1002/1097-0142(19940401)73:7<1785::aid-cncr2820730703>3.0.co;2-0
PMID:7907940
Abstract

BACKGROUND

During the last two decades, a rising incidence of adenocarcinoma of the esophagus has been observed in the Western world. The prognostic relevance of tumor-biological factors, such as DNA ploidy or c-erbB-2 overexpression, for overall survival following complete resection is still unknown.

METHODS

In a retrospective study of 80 patients with adenocarcinoma of Barrett's esophagus, the prognostic significance of flow cytometric DNA ploidy determination was investigated. Overexpression of c-erbB-2 oncoprotein was studied by immunohistochemical alkaline phosphatase-antialkaline phosphatase staining of formalin fixed, paraffin embedded tissue sections of the primary tumor.

RESULTS

The rate of aneuploidy was 86%. Aneuploidy was significantly correlated with lymph node metastases only. c-erbB-2 oncoprotein overexpression of the primary tumor was detected in 15 patients (19%). A significant correlation was seen between c-erbB-2 overexpression and depth of tumor invasion, lymph node involvement, distant metastases, and status of residual tumor after resection (R category, International Union Against Cancer [UICC], 1987). All primary tumors with c-erbB-2 oncoprotein overexpression were aneuploid. In a multivariate Cox regression analysis for overall survival of those 62 patients (78%) whose tumor resection was macroscopically and microscopically complete (R0-UICC), depth of invasion, distant metastases, and c-erbB-2 overexpression were independent prognostic factors. The relative risk of death due to recurrence was nearly identical for patients with either c-erbB-2 oncoprotein overexpression or distant metastases: 4.06 (1.4-11.8) and 3.94 (1.6-9.5). In a multivariate Cox regression analysis of the subgroup of lymph node-negative patients (n = 26), the ploidy status of the primary tumor (defined as near-diploid plus tetraploid versus aneuploid plus multiploid) was the only independent prognostic factor for overall survival.

CONCLUSIONS

These findings demonstrate that DNA ploidy as well as c-erbB-2 oncoprotein overexpression are valuable prognostic factors in patients with adenocarcinoma of Barrett's esophagus after complete tumor resection.

摘要

背景

在过去二十年中,西方世界食管腺癌的发病率呈上升趋势。肿瘤生物学因素,如DNA倍体或c-erbB-2过表达,对完全切除术后总生存的预后相关性仍不清楚。

方法

在一项对80例巴雷特食管腺癌患者的回顾性研究中,调查了流式细胞术测定DNA倍体的预后意义。通过对原发性肿瘤福尔马林固定、石蜡包埋组织切片进行免疫组化碱性磷酸酶-抗碱性磷酸酶染色,研究c-erbB-2癌蛋白的过表达情况。

结果

非整倍体率为86%。非整倍体仅与淋巴结转移显著相关。15例患者(19%)检测到原发性肿瘤c-erbB-2癌蛋白过表达。c-erbB-2过表达与肿瘤浸润深度、淋巴结受累情况、远处转移以及切除后残余肿瘤状态(R分类,国际抗癌联盟[UICC],1987)之间存在显著相关性。所有c-erbB-2癌蛋白过表达的原发性肿瘤均为非整倍体。在对62例(78%)肿瘤切除在宏观和微观上均完整(R0-UICC)的患者进行的总生存多因素Cox回归分析中,浸润深度、远处转移和c-erbB-2过表达是独立的预后因素。c-erbB-2癌蛋白过表达或远处转移患者因复发导致死亡的相对风险几乎相同:分别为4.06(1.4 - 11.8)和3.94(1.6 - 9.5)。在对淋巴结阴性患者亚组(n = 26)进行的多因素Cox回归分析中,原发性肿瘤的倍体状态(定义为近二倍体加四倍体与非整倍体加多倍体)是总生存的唯一独立预后因素。

结论

这些发现表明,DNA倍体以及c-erbB-2癌蛋白过表达是巴雷特食管腺癌患者肿瘤完全切除术后有价值的预后因素。

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