Kuniyasu Hiroki, Ukai Rinzo, Johnston Dennis, Troncoso Patricia, Fidler Isaiah J, Pettaway Curtis A
Department of Oncological Pathology, Cancer Center, Nara Medical University, Kashihara, Japan.
Clin Cancer Res. 2003 Jun;9(6):2185-94.
To determine whether the expression ratio of matrix metalloproteinase (MMP) to E-cadherin mRNA (MMP:E-cadherin) in biopsy (BX) samples of prostate cancer correlate with that of radical prostatectomy (RP) specimens and assists in predicting pathologic stage.
The mRNA expression levels for MMP-2 and -9 and of E-cadherin were determined by a colorimetric in situ hybridization assay in 44 paired BX and RP specimens. Clinical stage, BX Gleason score (GS), total length of cancer in BX cores, and serum prostate-specific antigen levels were also assessed.
Clinical stage was confined in 39 of 44 (89%) patients. Subsequent to RP, however, only 17 of 44 (39%) patients had proven organ-confined disease (pT2). BX GSs agreed with the RP GS in 77% of RP specimens. We found a strong correlation between BX and RP MMP:E-cadherin ratios (correlation coefficient = 0.755). The ratio increased as the GS increased and pathologic stage advanced (pT2 versus >/= pT3). Increasing clinical stage, GS, and serum prostate-specific antigen were significantly associated with advanced cancer at RP (P = 0.004-0.0001). The BX MMP:E-cadherin ratio, however, exhibited the strongest association with pathologic stage and independently predicted the status of 89% of the RP cases based on a BX ratio of <6 (predicted stage pT2 cancer at RP) versus >/=6 (predicted stage >/= pT3 at RP).
The BX MMP:E-cadherin ratio represents a novel prognostic assay for predicting stage of cancer at RP. These data provide proof of principle for directly assessing the biological potential of prostate cancer using molecular strategies in patient's specimens.
确定前列腺癌活检（BX）样本中基质金属蛋白酶（MMP）与E-钙黏蛋白mRNA的表达比值（MMP:E-钙黏蛋白）是否与根治性前列腺切除术（RP）标本中的该比值相关，并有助于预测病理分期。
采用比色原位杂交法测定44对BX和RP标本中MMP-2、MMP-9及E-钙黏蛋白的mRNA表达水平。同时评估临床分期、BX Gleason评分（GS）、BX芯针活检标本中癌组织的总长度以及血清前列腺特异性抗原水平。
44例患者中有39例（89%）临床分期局限。然而，RP术后，44例患者中仅有17例（39%）被证实为器官局限性疾病（pT2）。77%的RP标本中BX GS与RP GS一致。我们发现BX和RP的MMP:E-钙黏蛋白比值之间存在强相关性（相关系数 = 0.755）。该比值随GS增加和病理分期进展而升高（pT2与≥pT3相比）。临床分期增加、GS升高以及血清前列腺特异性抗原水平升高与RP时的晚期癌症显著相关（P = 0.004 - 0.0001）。然而，BX的MMP:E-钙黏蛋白比值与病理分期的相关性最强，基于BX比值<6（预测RP时为pT2期癌症）与≥6（预测RP时为≥pT3期），该比值独立预测了89%的RP病例的状态。
BX的MMP:E-钙黏蛋白比值是预测RP时癌症分期的一种新的预后检测方法。这些数据为在患者标本中使用分子策略直接评估前列腺癌的生物学潜能提供了原理证明。
