The relative mRNA expression levels of matrix metalloproteinase to E-cadherin in prostate biopsy specimens distinguishes organ-confined from advanced prostate cancer at radical prostatectomy.
The relative mRNA expression levels of matrix metalloproteinase to E-cadherin in prostate biopsy specimens distinguishes organ-confined from advanced prostate cancer at radical prostatectomy.
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发表时间：
2003-06
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通讯作者：
H. Kuniyasu;R. Ukai;D. Johnston;P. Troncoso;I. Fidler;C. Pettaway
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作者：
H. Kuniyasu;R. Ukai;D. Johnston;P. Troncoso;I. Fidler;C. Pettaway
目的探讨前列腺癌活检(BX)标本中基质金属蛋白酶(MMPs)与E-钙粘蛋白(E-cadherin)的表达比值(MMP值：E-Cadherin)与前列腺癌根治性切除术(RP)标本中基质金属蛋白酶(MMPs)与E-钙粘蛋白(E-Cadherin)的比值是否存在相关性，以帮助判断前列腺癌的病理分期。实验设计采用比色原位杂交法检测44例BX和RP标本中基质金属蛋白酶-2、-9和E-钙粘蛋白的mRNA表达水平。临床分期、BX Gleason评分(GS)、BX核心肿瘤总长度和血清前列腺特异性抗原水平也被评估。结果44例患者中39例(89%)临床分期受限。然而，在RP之后，44名患者中只有17名(39%)被证实患有器官受限疾病(Pt2)。BX-GSS与RP-GS的符合率为77%。我们发现BX与RP、基质金属蛋白酶：E-钙粘附素的比值有很强的相关性(相关系数=0.755)。这一比例随着GS的增加和病理分期的推进而增加(pt2与>；/=pt3)。增加临床分期、GS和血清前列腺特异性抗原与RP期晚期癌症显著相关(P=0.004-0.0001)。然而，BX-MMP：E-钙粘素比率与病理分期的相关性最强，并且基于BX比率/=6独立预测89%的RP病例的状态(在RP预测分期>；/=PT3)。结论BX-MMP值与E-钙粘附素比值是一种新的预测肿瘤分期的新指标。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力提供了原则证据。
PURPOSE 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. EXPERIMENTAL DESIGN 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. RESULTS 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 >/= pT3 at RP). CONCLUSION 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.