Prediction of pelvic lymph node metastasis by the ratio of cathepsin B to stefin A in patients with prostate carcinoma
Prediction of pelvic lymph node metastasis by the ratio of cathepsin B to stefin A in patients with prostate carcinoma
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DOI：
10.1002/cncr.10604
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发表时间：
2002-06-15
期刊：
影响因子：
6.2
通讯作者：
Gleason, DF
中科院分区：
文献类型：
--
作者：
Sinha, AA;Quast, BJ;Gleason, DF
背景病理分级和/或组织学评分、前列腺癌细胞对前列腺包膜、边缘和/或精囊的浸润所指示的前列腺外延伸、血清总前列腺特异性抗原（PSA）、游离PSA、复合PSA水平和/或它们的比率、区域盆腔淋巴结转移和临床分期已被用于诊断和监测前列腺癌（PC）患者的治疗。格里森分级系统也用于对患者的疾病阶段进行分级/评分，从低到高的评分指示PC的进展。然而，格里森的系统不能用于区分生物侵略性PC在一个单一的格里森评分。我们的目的是通过利用也促进癌细胞侵入前列腺基质和转移到淋巴结的生物分子来鉴定个体Gleason评分内的侵袭性前列腺癌的亚群（或克隆）。收集97例PC患者和8例良性前列腺增生患者的标本。这些患者在明尼阿波利斯退伍军人事务医疗中心接受直肠切除术前未接受激素和/或化疗药物治疗。福尔马林固定、石蜡或石蜡包埋的前列腺组织切片用苏木精和伊红染色用于病理诊断，相邻切片染色用于免疫组化研究。我们还收集了患者的年龄、种族、前列腺外浸润、边缘状态、精囊和淋巴结癌细胞浸润、前列腺切除术的临床分期和死亡率/生存率数据，包括术前和术后血清总PSA和前列腺酸性磷酸酶浓度。使用配备Metamorph软件的基于计算机的图像分析系统定量小鼠或兔抗组织蛋白酶B（CB）抗体IgG和小鼠抗人stefin（半胱氨酸蛋白酶抑制剂）A IgG的免疫组织化学定位。CB和stefin A在个体Gleason评分内鉴定了PC的侵袭性和侵袭性较低的克隆。组织学和形态学相似的Gleason评分为6的肿瘤在CB与stefin A的比率方面是异质的（CB > stefin A，CB = stefin A，和CB < stefin A）。我们还发现CB和stefin A的比值（CB > stefin A）与盆腔淋巴结转移的发生率呈显著正相关（P = 0.0066），但与CB小于stefin A的比值和/或CB等于stefin A的比值无关。Gleason评分为7分的患者淋巴结阳性率高于Gleason评分为6分的患者。我们的数据表明，当CB的比例大于stefin A时，患者的死亡率增加。单个Gleason评分中的PC是一种异质性肿瘤，包含侵袭性和侵袭性较低的肿瘤的克隆或亚群，可以通过CB与stefin A的比值来定义。当CB的比值大于stefin A的比值时，可以鉴定出具有攻击性克隆的PC。当CB的比率小于stefin A的比率或当CB的比率等于stefin A的比率时，鉴定出较低侵袭性的克隆。CB/stefin A比值可用于PC的鉴别诊断和治疗。这是第一份报告，以确定表型的侵略性和侵略性较低的PC在格里森评分。(C)2002年美国癌症协会。
BACKGROUND. Pathologic grade and/or histologic score, extraprostatic extension indicated by invasion of the prostatic capsule, margin, and/or seminal vesicles by Prostate cancer cells, serum total prostate-specific antigen (PSA), free PSA, complexed PSA levels and/or their ratios, regional pelvic lymph node metastases, and clinical staging have been used to diagnose and monitor the treatment of prostate carcinoma (PC) patients. The Gleason grading system is also used to grade/score a patient's stage of disease, with lower to higher scores indicating progression of PC. However, Gleason's system cannot be used to distinguish biologically aggressive PCs within a single Gleason score. Our objective was to identify subpopulations (or clones) of aggressive prostate cancers within an individual Gleason score by utilizing biological molecule(s) that also facilitate cancer cell invasion to prostatic stroma and metastasis to the lymph nodes.MATERIALS AND METHODS. Specimens were collected from 97 patients with PC and from 8 patients with benign prostatic hyperplasia. These patients had not been treated with hormonal and/or chemotherapeutic agents before undergoing a prostatectomy at the Minneapolis Veterans Affairs Medical Center. Formalin-fixed, paraffin or paraplast-embedded prostate tissue sections were stained with hematoxylin and eosin for pathologic diagnosis and adjacent sections were stained for for immunohistochemical study. We also collected data on age, race, extraprostatic extension, margin status, seminal vesicle, and lymph node invasion by cancer cells, clinical stage at prostatectomy, and mortality/ survival data, including the available presurgery and postsurgery serum total PSA and prostatic acid phosphatase concentrations in patients. Immunohistochemical localization of mouse or rabbit anti-cathepsin B (CB) antibody IgG and mouse antihuman stefin (cystatin) A IgG was quantified using a computer-based image analysis system equipped with Metamorph software.RESULTS. CB and stefin A identified aggressive and less aggressive clones of PCs within an individual Gleason score. Tumors with a Gleason Score of 6 that are similar histologically and morphologically were heterogeneous with respect to the ratios of CB to stefin A (CB > stefin A, CB = stefin A, and CB < stefin A). We also found a significant positive association (P = 0.0066) between ratios of CB and stefin A (CB > stefin A) and the incidence of pelvic lymph node metastases, but not with ratios of CB less than stefin A and/or ratios of CB equal to stefin A. Patients with Gleason 7 PCs had a higher incidence of positive lymph nodes than those with Gleason Score 6 tumors. Our data indicated that mortality rates increased in patients when the ratios of CB were greater than stefin A.CONCLUSIONS. PC within an individual Gleason score is a heterogeneous tumor that contains clones or subpopulations of aggressive and less aggressive tumors that can be defined by the ratios of CB to stefin A. PC with an aggressive clone can be identified when the ratio of CB is greater than that of stefin A. Less aggressive clones are identified when the ratio of CB is less than that of stefin A or when the ratio of CB is equal to that of stefin A. The ratios of CB to stefin A can be used in the differential diagnosis and treatment of patients with PC. This is the first report to identify phenotypes of aggressive and less aggressive PCs within a Gleason score. (C) 2002 American Cancer Society.