Rijstenberg Lucia L, Harikumar Hridya, Verhoef Esther I, van den Bosch Thierry P P, Choiniere Roselyne, van Royen Martin E, van Leenders Geert J L H
Department of Pathology, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, The Netherlands.
Histopathology. 2025 Jun;86(7):1091-1100. doi: 10.1111/his.15414. Epub 2025 Jan 30.
Intraductal carcinoma (IDC) is an independent pathological parameter for adverse prostate cancer (PCa) outcome. Although most IDC are believed to originate from retrograde spread of established PCa, rare IDC cases may represent precursor lesions. The actual transition areas between intraductal and invasive cancer, however, have not yet been identified. Our objective was to identify intraductal-invasive PCa transitions using 2- and 3-dimensional microscopy.
Seventy-five samples from 46 radical prostatectomies with PCa were immunohistochemically stained for basal cell keratins. In 35 samples, atypical glands that were indistinguishable from invasive adenocarcinoma (IAC) had focal 34BE12-positive basal cells. These IAC-like glands were present adjacent to IDC and prostatic intra-epithelial neoplasia (PIN) in 21 of 45 (46.7%) and 16 of 58 (27.6%) cases, respectively. Whole-mount confocal imaging of immunofluorescent Ker5/18 double-stained and cleared 1-mm-thick intact tissues revealed spatial continuity between IDC, IAC-like glands and IAC with a gradual loss of basal cells. In 24 of 35 (68.6%) samples more than one IAC-like focus (median 3.0) was present.
We identified areas of spatial transition between PIN, IDC and IAC, characterised by remnant basal cells in IAC-like glands. Based on the coexistence of IDC and PIN, the gradual loss of basal cells in IAC-like glands and IAC-like glands' multifocality, we propose a novel hypothesis on intraductal carcinogenesis, which we term 'repetitive invasion, precursor progression' (RIPP).
导管内癌（IDC）是前列腺癌（PCa）不良预后的一个独立病理参数。尽管大多数IDC被认为起源于已确诊PCa的逆行播散，但罕见的IDC病例可能代表前驱病变。然而，导管内癌和浸润性癌之间的实际过渡区域尚未明确。我们的目标是使用二维和三维显微镜鉴定导管内-浸润性PCa的过渡区域。
对46例患有PCa的根治性前列腺切除术的75个样本进行基底细胞角蛋白免疫组化染色。在35个样本中，与浸润性腺癌（IAC）难以区分的非典型腺体有局灶性34BE12阳性基底细胞。这些IAC样腺体分别在45例中的21例（46.7%）和58例中的16例（27.6%）中与IDC和前列腺上皮内瘤变（PIN）相邻。对免疫荧光Ker5/18双重染色并清除的1毫米厚完整组织进行全层共聚焦成像，显示IDC、IAC样腺体和IAC之间存在空间连续性，同时基底细胞逐渐消失。在35个样本中的24个（68.6%）中存在不止一个IAC样病灶（中位数为3.0）。
我们鉴定了PIN、IDC和IAC之间的空间过渡区域，其特征是IAC样腺体中存在残留基底细胞。基于IDC和PIN的共存、IAC样腺体中基底细胞的逐渐消失以及IAC样腺体的多灶性，我们提出了一种关于导管内致癌作用的新假说，我们称之为“重复侵袭，前驱进展”（RIPP）。
