Petraki C D, Gregorakis A K, Papanastasiou P A, Karavana V N, Luo L-Y, Diamandis E P
Departments of Pathology and Urology, Evangelismos Hospital, Athens, Greece.
Prostate Cancer Prostatic Dis. 2003;6(3):223-7. doi: 10.1038/sj.pcan.4500674.
Human kallikreins 6, 10 and 13 (hK6, hK10 and hK13) are expressed by many normal, mainly glandular tissues, including prostatic epithelium. Some kallikreins may function as tumor suppressors or are downregulated during cancer progression. The aim of this study was to evaluate the immunoexpression of these kallikreins in benign and malignant prostatic tissues and correlate their expression with prostate cancer (PC) prognosis. Included in the study were 25 cases of nonmalignant prostate and 179 cases of PC. Among them, 122 PC cases were immunostained for hK6, 94 for hK10 and 113 for hK13, respectively. The follow-up period for a subset of 68 patients who had undergone radical prostatectomy (RP) was 1-58 months (mean=13.4 +/- 1.7 and median=8.0 months). A cutoff value of 0.2 microg/l of serum PSA was established as a biochemical recurrence threshold. Follow-up information was available for 26/55 RP cases stained for hK6, 14/32 cases stained for hK10 and 25/59 cases stained for hK13. Gleason score (GS) 7 carcinomas were stratified as 7a and 7b, according to the primary grade. PC with GS 2-7a were histologically categorized as low malignant (LM) and PC with GS 7b-10 as high malignant (HM). The immunohistochemical method of streptavidin-biotin-peroxidase using monoclonal and polyclonal antibodies was performed. In the benign prostate and in prostatic intraepithelial neoplasia, a cytoplasmic immunostaining of varying intensity was evident. In PC, the immunoexpression of all kallikreins was decreased: 102/122 cases (84%) were positive for hK6, 73/94 (78%) for hK10 and 97/113 (86%) for hK13, respectively. A statistically significant difference in expression was found, in comparison to nonmalignant prostates (P=0.029, 0.009 and 0.045, respectively). Also, a positive correlation was observed between the immunoexpression of these three kallikreins. Concerning the histological grade, HM-PC expressed all three kallikreins with a slightly higher percentage than LM-PC: 79 vs 88% for hK6, 76 vs 79% for hK10 and 76 vs 92% for hK13. These differences were statistically significant only in the case of hK13 (P=0.024). Serum PSA did not correlate with kallikrein immunoexpression in PC. Furthermore, there was no significant correlation between kallikrein expression and pathological stage or recurrence, in the cases of RP. All three kallikreins are expressed in the nonmalignant and malignant prostate, with cancer tissues demonstrating slightly lower expression. Expression levels did not correlate with aggressiveness and they do not seem to have value for prostate cancer prognosis.
人激肽释放酶6、10和13（hK6、hK10和hK13）在包括前列腺上皮在内的许多正常主要是腺性组织中表达。一些激肽释放酶可能起肿瘤抑制作用，或在癌症进展过程中表达下调。本研究的目的是评估这些激肽释放酶在前列腺良性和恶性组织中的免疫表达，并将其表达与前列腺癌（PC）的预后相关联。研究纳入了25例非恶性前列腺病例和179例PC病例。其中，分别对122例PC病例进行hK6免疫染色，94例进行hK10免疫染色，113例进行hK13免疫染色。对68例行根治性前列腺切除术（RP）患者的随访期为1 - 58个月（平均 = 13.4 ± 1.7个月，中位数 = 8.0个月）。将血清PSA的临界值设定为0.2μg/l作为生化复发阈值。有26/55例hK6染色的RP病例、14/32例hK10染色的病例和25/59例hK13染色的病例可获得随访信息。根据主要分级，Gleason评分（GS）7级癌被分为7a和7b。GS 2 - 7a级的PC在组织学上归类为低恶性（LM），GS 7b - 10级的PC归类为高恶性（HM）。采用单克隆和多克隆抗体的链霉亲和素 - 生物素 - 过氧化物酶免疫组织化学方法。在良性前列腺和前列腺上皮内瘤变中，可见不同强度的细胞质免疫染色。在PC中，所有激肽释放酶的免疫表达均降低：hK6为102/122例（84%）阳性，hK10为73/94例（78%）阳性，hK13为97/113例（86%）阳性。与非恶性前列腺相比，发现表达存在统计学显著差异（分别为P = 0.029、0.009和0.045）。此外，观察到这三种激肽释放酶的免疫表达之间存在正相关。关于组织学分级，HM - PC表达所有三种激肽释放酶的百分比略高于LM - PC：hK6为79%对88%，hK10为76%对79%，hK13为76%对92%。这些差异仅在hK13的情况下具有统计学显著性（P = 0.024）。PC中的血清PSA与激肽释放酶免疫表达无关。此外，在RP病例中，激肽释放酶表达与病理分期或复发之间无显著相关性。所有三种激肽释放酶均在前列腺非恶性和恶性组织中表达，癌组织的表达略低。表达水平与侵袭性无关，似乎对前列腺癌预后无价值。
