组织蛋白酶D在卵巢癌中的预后价值及其与p53表达和微血管密度的相关性

Cathepsin D in ovarian cancer: prognostic value and correlation with p53 expression and microvessel density.

作者信息

Lösch A, Schindl M, Kohlberger P, Lahodny J, Breitenecker G, Horvat R, Birner P

机构信息

Clinical Institute of Pathology, University of Vienna, A-1090 Vienna, Austria.

出版信息

Gynecol Oncol. 2004 Feb;92(2):545-52. doi: 10.1016/j.ygyno.2003.11.016.

DOI:10.1016/j.ygyno.2003.11.016

PMID:14766246

Abstract

OBJECTIVE

Overexpression of ubiquitous lysosomal aspartyl protease cathepsin D (CD) is involved in the progression of cancer. This study investigates the prognostic value and the association of cathepsin D expression with clinicopathological parameters, p53 expression, and angiogenesis in ovarian cancer.

METHODS

Cathepsin D was determined immunohistochemically in 43 ovarian tumors of low malignant potential (LMP) and 80 invasive tumors FIGO stage I-IV. Results were correlated with clinicopathological characteristics, p53, and microvessel density (MVD). Survival analysis of cathepsin D expression and MVD was performed in invasive tumors.

RESULTS

Epithelial tumor cathepsin D expression was more common in LMP tumors (65.1%) compared to invasive tumors (43.7%; P = 0.02). In LMP tumors, stromal cathepsin D was associated with mucinous tumors (P = 0.01), whereas in invasive tumors, epithelial cathepsin D expression was associated with clear cell tumors (P = 0.003). Invasive tumor cathepsin D had a negative relation to p53 expression. In LMP tumors, stromal cathepsin D correlated with microvessel density (P = 0.03). Stromal cathepsin D expression was an independent prognostic factor for disease-free survival (DFS) in patients with invasive cancer (P = 0.03, Cox regression), while cathepsin D expression missed to be of prognostic value for overall survival (OS) in invasive ovarian cancer. MVD had no influence on survival in invasive ovarian cancer (P > 0.05).

CONCLUSION

Our study demonstrates a prognostic value of cathepsin D expression in invasive ovarian cancer, while cathepsin D expression in LMP tumors seems to be linked to angiogenesis. The relation among cathepsin D, p53 expression, and angiogenesis demonstrates biological differences between invasive ovarian cancer and LMP tumors.

摘要

目的

普遍存在的溶酶体天冬氨酸蛋白酶组织蛋白酶D（CD）的过表达与癌症进展有关。本研究调查组织蛋白酶D表达在卵巢癌中的预后价值及其与临床病理参数、p53表达和血管生成的关联。

方法

采用免疫组织化学法检测43例低恶性潜能（LMP）卵巢肿瘤和80例FIGO I-IV期浸润性肿瘤中的组织蛋白酶D。将结果与临床病理特征、p53和微血管密度（MVD）进行相关性分析。对浸润性肿瘤进行组织蛋白酶D表达和MVD的生存分析。

结果

与浸润性肿瘤（43.7%；P = 0.02）相比，上皮性肿瘤组织蛋白酶D表达在LMP肿瘤中更常见（65.1%）。在LMP肿瘤中，基质组织蛋白酶D与黏液性肿瘤相关（P = 0.01），而在浸润性肿瘤中，上皮组织蛋白酶D表达与透明细胞肿瘤相关（P = 0.003）。浸润性肿瘤组织蛋白酶D与p53表达呈负相关。在LMP肿瘤中，基质组织蛋白酶D与微血管密度相关（P = 0.03）。基质组织蛋白酶D表达是浸润性癌患者无病生存期（DFS）的独立预后因素（P = 0.03，Cox回归），而组织蛋白酶D表达对浸润性卵巢癌的总生存期（OS）无预后价值。MVD对浸润性卵巢癌的生存无影响（P > 0.05）。