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软组织肉瘤中p53蛋白的核免疫反应。一种可能的预后因素。

Nuclear immunoreaction of p53 protein in soft tissue sarcomas. A possible prognostic factor.

作者信息

Kawai A, Noguchi M, Beppu Y, Yokoyama R, Mukai K, Hirohashi S, Inoue H, Fukuma H

机构信息

Department of Orthopaedic Surgery, National Cancer Center Hospital, Tokyo, Japan.

出版信息

Cancer. 1994 May 15;73(10):2499-505. doi: 10.1002/1097-0142(19940515)73:10<2499::aid-cncr2820731008>3.0.co;2-g.

Abstract

BACKGROUND

Tumor suppressor gene p53, located on the short arm of chromosome 17, frequently mutates in various types of cancers and plays a critical role in the multiple stages of carcinogenesis. However, there is little information about the clinicopathologic significance of alterations of the p53 gene in soft tissue sarcomas (STS).

METHODS

Because it is known that nuclear accumulation of p53 protein correlates closely with the presence of mutations in the p53 gene, immunohistochemical detection of this protein was performed. A polyclonal antibody (RSP-53) raised against synthetic human p53 peptide was used to detect nuclear accumulation of the protein. Pathologic specimens of 96 patients with STS were collected from the surgical pathology files of the National Cancer Center Hospital and examined.

RESULTS

Nuclear accumulation of p53 protein was detected in 31 (32.3%) patients. The percentage of patients with a positive immunoreaction was high in patients with malignant schwannoma (100%), rhabdomyosarcoma (71.4%), and synovial sarcoma (50.0%), whereas it was low in patients with liposarcoma (13.6%) and 0% in those with fibrosarcoma. It was closely associated with the histologic grade of malignancy (grade 1, 12.0%; grade 2, 30.8%; grade 3, 44.4%) and the patient's age (younger than 40 years, 46.9%; 40 years of age or older, 25.0%). Both overall and metastasis-free survival rates were significantly lower for patients with a nuclear p53 immunoreaction than for those without it.

CONCLUSIONS

The nuclear p53 immunoreaction is considered a marker of tumor aggressiveness and appears to be a useful prognostic factor for STS.

摘要

背景

肿瘤抑制基因p53位于17号染色体短臂,在多种癌症中频繁发生突变,在致癌作用的多个阶段发挥关键作用。然而,关于软组织肉瘤(STS)中p53基因改变的临床病理意义的信息较少。

方法

由于已知p53蛋白的核积累与p53基因中的突变密切相关,因此对该蛋白进行了免疫组织化学检测。使用针对合成人p53肽产生的多克隆抗体(RSP - 53)检测该蛋白的核积累。从国立癌症中心医院的手术病理档案中收集了96例STS患者的病理标本并进行检查。

结果

在31例(32.3%)患者中检测到p53蛋白的核积累。恶性神经鞘瘤患者(100%)、横纹肌肉瘤患者(71.4%)和滑膜肉瘤患者(50.0%)中免疫反应阳性患者的百分比很高,而脂肪肉瘤患者中该百分比很低(13.6%),纤维肉瘤患者中为0%。它与组织学恶性程度密切相关(1级,12.0%;2级,30.8%;3级,44.4%)以及患者年龄(小于40岁,46.9%;40岁及以上,25.0%)。核p53免疫反应阳性的患者的总生存率和无转移生存率均显著低于无核p53免疫反应的患者。

结论

核p53免疫反应被认为是肿瘤侵袭性的标志物,似乎是STS的一个有用的预后因素。

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