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局部晚期喉癌的流式细胞术DNA分析及溶酶体组织蛋白酶B和L。与临床病理参数的关系及预后意义。

Flow cytometric DNA analysis and lysosomal cathepsins B and L in locally advanced laryngeal cancer. Relationship with clinicopathologic parameters and prognostic significance.

作者信息

Russo A, Bazan V, Gebbia N, Pizzolanti G, Tumminello F M, Dardanoni G, Ingria F, Restivo S, Tomasino R M, Leto G

机构信息

Institute of Otorhinolaringology B, School of Medicine, University of Palermo, Italy.

出版信息

Cancer. 1995 Nov 15;76(10):1757-64. doi: 10.1002/1097-0142(19951115)76:10<1757::aid-cncr2820761012>3.0.co;2-h.

DOI:10.1002/1097-0142(19951115)76:10<1757::aid-cncr2820761012>3.0.co;2-h
PMID:8625044
Abstract

BACKGROUND

The traditional factors of locally advanced laryngeal squamous cell carcinoma (LSCC) have limited predictive value for the identification of high risk patients. Therefore, it is extremely important to define prognostic factors that identify the more aggressive types. Reliable and reproducible prognostic indicators are being investigated to help clinicians identify high risk groups and address more rational treatment.

METHODS

Flow cytometric DNA ploidy and S-phase fraction (SPF) measurements were performed on frozen tumor tissues from a consecutive series of 71 patients with Stage III and IV LSCC: Lysosomal cathepsin B and L activity levels were determined biochemically in matched paired sets of tumor tissue and normal mucosa samples.

RESULTS

By univariate analysis, lymph node positivity, poor histologic differentiation, DNA aneuploidy, high SPF, and high tumor/mucosa ratio of cathepsin B activity were significantly related to risk of relapse, whereas only DNA aneuploidy and high SPF proved to be significantly related to risk of death. Multivariate analysis showed that high histologic grade and high SPF values (> 15.1%) were independent prognostic factors related to risk of relapse (relative risk [RR] = 3.54; 95% confidence limits [CL] = 1.05-12.0; and RR = 4.22; CL = 1.54-11.6, respectively), whereas only high SPF was related to risk of death (RR = 3.63; CL = 1.17-11.3).

CONCLUSIONS

S-phase fraction is an independent predictor of relapse free and overall survival in patients with locally advanced LSCC. On the basis of these findings, SPF should be used in addition to other established prognostic factors to refine the prognostic assessment of these patients further. More studies are needed for a better evaluation of the prognostic significance of DNA ploidy and that of lysosomal cysteine proteinases in these tumors.

摘要

背景

局部晚期喉鳞状细胞癌(LSCC)的传统因素对识别高危患者的预测价值有限。因此,定义能够识别更具侵袭性类型的预后因素极为重要。目前正在研究可靠且可重复的预后指标,以帮助临床医生识别高危组并进行更合理的治疗。

方法

对连续71例III期和IV期LSCC患者的冷冻肿瘤组织进行流式细胞术DNA倍体和S期分数(SPF)测量:采用生化方法测定配对的肿瘤组织和正常黏膜样本中溶酶体组织蛋白酶B和L的活性水平。

结果

单因素分析显示,淋巴结阳性、组织学分化差、DNA非整倍体、高SPF以及组织蛋白酶B活性的肿瘤/黏膜高比值与复发风险显著相关,而只有DNA非整倍体和高SPF与死亡风险显著相关。多因素分析表明,高组织学分级和高SPF值(>15.1%)是与复发风险相关的独立预后因素(相对风险[RR]=3.54;95%置信区间[CL]=1.05 - 12.0;以及RR = 4.22;CL = 1.54 - 11.6),而只有高SPF与死亡风险相关(RR = 3.63;CL = 1.17 - 11.3)。

结论

S期分数是局部晚期LSCC患者无复发生存和总生存的独立预测指标。基于这些发现,除其他已确定的预后因素外,还应使用SPF进一步完善对这些患者的预后评估。需要更多研究以更好地评估DNA倍体和溶酶体半胱氨酸蛋白酶在这些肿瘤中的预后意义。

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