Shibata Kiyosumi, Kikkawa Fumitaka, Suzuki Yuka, Mizokami Yayoi, Kajiyama Hiroaki, Ino Kazuhiko, Nomura Seiji, Nagasaka Tetsuro, Mizutani Shigehiko
Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Oncology. 2004;66(4):288-95. doi: 10.1159/000078329.
Placental leucine aminopeptidase (P-LAP) is a cell surface aminopeptidase (oxytocinase). We cloned P-LAP cDNA and found a widespread tissue distribution of P-LAP. Since P-LAP can degrade several small peptide hormones such as oxytocin, this enzyme may affect many cellular functions of carcinoma cells as well as normal cells. This study investigated whether the expression of P-LAP correlates with clinicopathologic factors and prognosis in patients with endometrial endometrioid adenocarcinoma.
Histologic sections of formalin-fixed, paraffin-embedded specimens from 99 primary endometrial carcinomas were stained for P-LAP using polyclonal P-LAP antibody. Disease-free survival and other clinicopathologic characteristics were analyzed according to the intensity of P-LAP staining.
Of 99 cases, 69 (69.7%) showed specific P-LAP immunostaining. We found a positive correlation between the expression of P-LAP and histological grade (p < 0.01), surgical stage of the disease (p = 0.02), myometrial invasion (p = 0.01), lymph node involvement (p < 0.01), and vascular infiltration (p < 0.01). In patients who had strongly positive P-LAP staining, the disease-free interval was significantly lower than in patients who had negative or weakly positive P-LAP staining (p < 0.01). Multivariate analysis demonstrated that strongly immunoreactive P-LAP (odds ratio, 12.8; 95% confidence interval, 2.84-58.8; p < 0.01) and surgical stage (odds ratio, 8.78; 95% confidence interval, 2.77-27.8; p < 0.01) are independent prognostic factors.
This study suggests P-LAP as an independent prognosticator of clinical outcome in patients with endometrial carcinoma. Therefore, assessment of the P-LAP status provides clinically useful prognostic information in patients with endometrial carcinoma.
胎盘亮氨酸氨肽酶（P-LAP）是一种细胞表面氨肽酶（催产素酶）。我们克隆了P-LAP cDNA，并发现P-LAP在组织中广泛分布。由于P-LAP可降解多种小肽激素，如催产素，因此该酶可能影响癌细胞以及正常细胞的许多细胞功能。本研究调查了P-LAP的表达与子宫内膜样腺癌患者的临床病理因素及预后是否相关。
用多克隆P-LAP抗体对99例原发性子宫内膜癌的福尔马林固定、石蜡包埋标本的组织切片进行P-LAP染色。根据P-LAP染色强度分析无病生存期及其他临床病理特征。
99例中，69例（69.7%）显示特异性P-LAP免疫染色。我们发现P-LAP的表达与组织学分级（p<0.01）、疾病手术分期（p = 0.02）、肌层浸润（p = 0.01）、淋巴结受累（p<0.01）和血管浸润（p<0.01）呈正相关。P-LAP染色强阳性的患者，其无病间期显著低于P-LAP染色阴性或弱阳性的患者（p<0.01）。多因素分析表明，P-LAP强免疫反应性（比值比，12.8；95%置信区间，2.84 - 58.8；p<0.01）和手术分期（比值比，8.78；95%置信区间，2.77 - 27.8；p<0.01）是独立的预后因素。
本研究提示P-LAP可作为子宫内膜癌患者临床结局的独立预后指标。因此，评估P-LAP状态可为子宫内膜癌患者提供临床有用的预后信息。
