Lösch A, Schindl M, Kohlberger P, Lahodny J, Breitenecker G, Horvat R, Birner P
Clinical Institute of Pathology, University of Vienna, A-1090 Vienna, Austria.
Gynecol Oncol. 2004 Feb;92(2):545-52. doi: 10.1016/j.ygyno.2003.11.016.
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.
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.
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).
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.
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。
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。
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）。
我们的研究表明组织蛋白酶D表达在浸润性卵巢癌中具有预后价值，而LMP肿瘤中的组织蛋白酶D表达似乎与血管生成有关。组织蛋白酶D、p53表达和血管生成之间的关系表明浸润性卵巢癌和LMP肿瘤之间存在生物学差异。
