Urokinase Plasminogen Activator Receptor (uPAR): A Potential Indicator of Invasion for In Situ Breast Cancer.

Urokinase Plasminogen Activator Receptor (uPAR): A Potential Indicator of Invasion for In Situ Breast Cancer.
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DOI:
10.1046/j.1524-4741.2000.99025.x
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发表时间:
2000-03-01
期刊:
The breast journal
影响因子:
--
通讯作者:
Sloan-Stakleff, Kimberly D.
Sloan-Stakleff, Kimberly D.
中科院分区:
其他
文献类型:
--
作者:
Guyton, Daniel P.;Evans, Douglas M.;Sloan-Stakleff, Kimberly D.

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尿激酶纤溶酶原激活物(uPA)及其细胞受体(uPAR)是肿瘤侵袭转移过程中的重要介质。导管原位癌(DCIS)的分类是由于缺乏对相邻间质的浸润,但明确的组织学特征尚未确定表明细胞浸润的倾向。由于DCIS的复发可能性,其治疗方法仍存在争议。我们假设uPA和uPAR可能代表DCIS复发的新预测因子。10例正常、10例增生和70例DCIS患者的组织标本。使用小鼠抗人uPA和uPAR抗体对这些区域的代表性切片进行免疫组织学染色。通过密度图像分析评估染色强度。将原位患者的灰度值与正常平均值进行比较,以确定染色强度是否正常或明显高于正常(p < 0.05)。DCIS组织中uPA和uPAR的染色强度是不均匀的。uPAR高染色强度患者(28/70 = 40%)的复发率(15/28 = 54%)高于uPA高染色强度患者(19/70 = 28%,17/50 = 34%)。此外,uPA和uPAR合并高染色的患者(11/19 = 60%)的复发率为55%,而高uPA/正常uPAR的复发率为0%。DCIS对uPAR的免疫组织学评估,单独和联合uPA与浸润性乳腺癌的复发有显著相关性。uPAR在DCIS病变中的评价可能为乳腺癌复发提供新的预后指标。
Urokinase plasminogen activator (uPA) and its cellular receptor (uPAR) are important mediators in the cellular process of cancer invasion and metastasis. Ductal carcinoma in situ (DCIS) is classified by lack of invasion into the adjacent stroma, yet definitive histologic features have not been identified to indicate the propensity for cellular invasion. Therapy for DCIS remains controversial because of the probability for recurrence. We hypothesized that uPA and uPAR may represent new predictors for recurrence of DCIS. Tissue specimens were obtained from 10 normal, 10 hyperplasia, and 70 patients with DCIS. Representative sections of the regions were mounted and stained by immunohistologic techniques using mouse anti-human uPA and uPAR antibodies. Stain intensities were assessed by densitometry image analysis. Gray scale values for in situ patients were compared to normal averages to determine whether staining intensities were normal or significantly higher (p < 0.05) than normal. DCIS tissues were heterogeneous for stain intensities of uPA and uPAR. Patients with high stain intensities for uPAR (28/70 = 40%) correlated with a higher recurrence rate (15/28 = 54%) than with patients having high stains for uPA (19/70 = 28% with 17/50 = 34% recurrence). In addition, patients with combined high stains for uPA and uPAR (11/19 = 60%) showed a recurrence rate of 55% compared to high uPA/normal uPAR with 0% recurrence. Immunohistologic evaluation of DCIS for uPAR, alone and in combination with uPA, significantly correlates with recurrence of invasive breast carcinoma. Evaluation of uPAR among DCIS lesions may provide a new prognostic indicator for recurrence of breast carcinoma.