ERG and PTEN status of isolated high-grade PIN occurring in cystoprostatectomy specimens without invasive prostatic adenocarcinoma.

ERG and PTEN status of isolated high-grade PIN occurring in cystoprostatectomy specimens without invasive prostatic adenocarcinoma.
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DOI:
10.1016/j.humpath.2016.04.017
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发表时间:
2016-09
期刊:
影响因子:
3.3
通讯作者:
Lotan TL
Lotan TL
中科院分区:
医学3区
文献类型:
--
作者:
Morais CL;Guedes LB;Hicks J;Baras AS;De Marzo AM;Lotan TL

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高级别前列腺上皮内瘤变(HGPIN)被广泛认为是侵袭性前列腺癌的先兆。然而,最近的分子研究表明,侵袭性腺癌向原有前列腺癌导管的逆行扩散在形态上可以模仿HGPIN。因此,以往关于前列腺癌根治术或针吸活检并发浸润性癌的形态特征的分子研究可能部分混淆了浸润性肿瘤的导管内扩散。为了评估可能代表前列腺真正前驱病变的HGPIN病灶中ERG和PTEN的状态,我们研究了2009至2014年间在Johns Hopkins进行的膀胱前列腺切除术中发生的孤立的HGPIN,这些患者没有相关的侵袭性腺癌。在344例膀胱前列腺切除术中,33%(115/344)的部分前列腺癌(平均10块/例)含有浸润性前列腺癌,因此被排除在研究之外。在其余未采集癌标本的病例中,32%(73/229)显示了133个不同的HGPIN病灶,并使用基因验证方案对ERG和PTEN进行了免疫组织化学染色。在可评价染色的HGPIN病灶中,ERG阳性率为7%(8/107)。HGPIN病变中未见PTEN丢失(0/88)。由于膀胱前列腺切除术中这些孤立的HGPIN病灶不太可能代表侵袭性肿瘤的逆行扩散,我们的研究表明,在前列腺中少数潜在的肿瘤前驱病变中存在ERG重排,而不是PTEN丢失。
High grade prostatic intraepithelial neoplasia (HGPIN) is widely believed to represent a precursor to invasive prostatic adenocarcinoma. However, recent molecular studies have suggested that retrograde spread of invasive adenocarcinoma into pre-existing prostatic ducts can morphologically mimic HGPIN. Thus, previous molecular studies characterizing morphologically-identified HGPIN occurring in radical prostatectomies or needle biopsies with concurrent invasive carcinoma may be partially confounded by intraductal spread of invasive tumor. To assess ERG and PTEN status in HGPIN foci likely to represent true precursor lesions in the prostate, we studied isolated HGPIN occurring without associated invasive adenocarcinoma in cystoprostatectomies performed at Johns Hopkins between 2009 and 2014. Of 344 cystoprostatectomies, 33% (115/344) contained invasive prostatic adenocarcinoma in the partially submitted prostate (10 blocks/case on average) and were excluded from the study. Of the remaining cases without sampled cancer, 32% (73/229) showed 133 separate foci of HGPIN and were immunostained for ERG and PTEN using genetically validated protocols. Of foci of HGPIN with evaluable staining, 7% (8/107) were positive for ERG. PTEN loss was not seen in any HGPIN lesion (0/88). Because these isolated HGPIN foci at cystoprostatectomy are unlikely to represent retrograde spread of invasive tumor, our study suggests that ERG rearrangement, but not PTEN loss, is present in a minority of potential neoplastic precursor lesions in the prostate.