Sinha Akhouri A, Morgan Jenifer L, Betre Konjit, Wilson Michael J, Le Chap, Marks Leonard S
Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Anticancer Res. 2008 Jul-Aug;28(4B):2271-7.
Japanese-American (J-A) men who have immigrated to the U.S.A. and acquired the Western lifestyle usually have more invasive prostate cancer (PCa) than native Japanese (NJ) living in Japan. The specific reasons for these differences remain unknown. The objective of this study was to examine immunostainings of cathepsin B (CB) and its endogenous inhibitor stefin A (SA) in tissue microarray (TMA) and radical prostatectomy (RP) tissue sections in the hope of obtaining insights into the invasiveness of PCa in Japanese patients.
TMA and RP sections were evaluated in 50 men (25 NJ and 25 J-A) for CB and SA reaction products. The CB and SA immunostainings were imaged directly from microscope slides to a computer using a high performance charge coupled device (CCD) digital camera, quantified using Metamorph software, analyzed using the two-sample t-test, and confirmed by multiple regression analysis.
The CB and SA proteins were localized in the carcinomatous glands and isolated cancer cells in the TMA and RP sections. The Gleason scores and pre-surgery serum total prostate-specific antigen (PSA) levels did not differ significantly in the NJ and J-A patients (p = 0.14, p = 0.16, respectively). The Chi-square analysis of clinical stage versus place of birth showed that the NJ patients had significantly more T2a and T2b clinical stages than the J-A patients who had more advanced T2c and T3a stages (p = 0.003). The CB and SA immunostainings and their ratios in Gleason score 6 tumors did not show any difference, but the CB:SA ratios in score > or = 7 tumors approached significance levels.
The overall matching of specimens according to the Gleason grade/score, pre-RP serum total PSA levels, clinical stage and age prior to evaluation of immunostainings greatly minimizes subjectivity associated with the evaluation of markers in this ethnic sub-population of PCa patients. CB and SA immunostaining is similar in Japanese patients who have organ-confined and moderately-differentiated PCa. Analysis of the reaction product data provides indirect evidence that invasiveness of PCa is similar in the two Japanese patient populations.
移民到美国并采用西方生活方式的日裔美国(J-A)男性通常比生活在日本的本土日本人(NJ)患侵袭性前列腺癌(PCa)的几率更高。这些差异的具体原因尚不清楚。本研究的目的是检查组织微阵列(TMA)和根治性前列腺切除术(RP)组织切片中组织蛋白酶B(CB)及其内源性抑制剂丝氨酸蛋白酶抑制剂A(SA)的免疫染色情况,以期深入了解日本患者PCa的侵袭性。
对50名男性(25名NJ和25名J-A)的TMA和RP切片进行CB和SA反应产物评估。使用高性能电荷耦合器件(CCD)数码相机将CB和SA免疫染色直接从显微镜载玻片成像到计算机上,使用MetaMorph软件进行定量分析,采用两样本t检验进行分析,并通过多元回归分析进行确认。
CB和SA蛋白定位于TMA和RP切片中的癌性腺管和单个癌细胞中。NJ和J-A患者的Gleason评分和术前血清总前列腺特异性抗原(PSA)水平无显著差异(分别为p = 0.14,p = 0.16)。临床分期与出生地的卡方分析表明,NJ患者的T2a和T2b临床分期显著多于J-A患者,而J-A患者的T2c和T3a期更为 advanced(p = 0.003)。Gleason评分为6分的肿瘤中CB和SA免疫染色及其比例无差异,但评分≥7分的肿瘤中CB:SA比例接近显著水平。
在评估免疫染色之前,根据Gleason分级/评分、RP术前血清总PSA水平、临床分期和年龄对标本进行总体匹配,可极大地减少在该PCa患者种族亚群中评估标志物时的主观性。在患有器官局限性和中度分化PCa的日本患者中,CB和SA免疫染色相似。对反应产物数据的分析提供了间接证据,表明这两个日本患者群体中PCa的侵袭性相似。