Arya Manit, Thrasivoulou Christopher, Henrique Rui, Millar Michael, Hamblin Ruth, Davda Reena, Aare Kristina, Masters John R, Thomson Calum, Muneer Asif, Patel Hitendra R H, Ahmed Aamir
Division of Surgery, University College Hospital, London, United Kingdom and The Barts Cancer Institute, Queen Mary University of London, London, United Kingdom.
Research Department of Cell and Developmental Biology, The Centre for Cell and Molecular Dynamics, Rockefeller Building, University College London, London, United Kingdom.
PLoS One. 2015 Apr 22;10(4):e0124395. doi: 10.1371/journal.pone.0124395. eCollection 2015.
Penile squamous cell carcinoma (PeCa) is a rare malignancy and little is known regarding the molecular mechanisms involved in carcinogenesis of PeCa. The Wnt signaling pathway, with the transcription activator ß-catenin as a major transducer, is a key cellular pathway during development and in disease, particularly cancer. We have used PeCa tissue arrays and multi-fluorophore labelled, quantitative, immunohistochemistry to interrogate the expression of WNT4, a Wnt ligand, and three targets of Wnt-ß-catenin transcription activation, namely, MMP7, cyclinD1 (CD1) and c-MYC in 141 penile tissue cores from 101 unique samples. The expression of all Wnt signaling proteins tested was increased by 1.6 to 3 fold in PeCa samples compared to control tissue (normal or cancer adjacent) samples (p<0.01). Expression of all proteins, except CD1, showed a significant decrease in grade II compared to grade I tumors. High magnification, deconvolved confocal images were used to measure differences in co-localization between the four proteins. Significant (p<0.04-0.0001) differences were observed for various permutations of the combinations of proteins and state of the tissue (control, tumor grades I and II). Wnt signaling may play an important role in PeCa and proteins of the Wnt signaling network could be useful targets for diagnosis and prognostic stratification of disease.
阴茎鳞状细胞癌（PeCa）是一种罕见的恶性肿瘤，关于其致癌过程中涉及的分子机制，人们知之甚少。以转录激活因子β-连环蛋白作为主要转导分子的Wnt信号通路，是发育过程以及疾病尤其是癌症中的关键细胞通路。我们使用阴茎癌组织芯片以及多荧光团标记的定量免疫组织化学方法，检测了101个独特样本的141个阴茎组织核心中Wnt配体WNT4以及Wnt-β-连环蛋白转录激活的三个靶标，即基质金属蛋白酶7（MMP7）、细胞周期蛋白D1（CD1）和c-MYC的表达。与对照组织（正常组织或癌旁组织）样本相比，PeCa样本中所有检测的Wnt信号蛋白的表达增加了1.6至3倍（p<0.01）。除CD1外，所有蛋白的表达在II级肿瘤中与I级肿瘤相比均显著降低。使用高倍放大、解卷积共聚焦图像来测量这四种蛋白之间共定位的差异。在蛋白组合和组织状态（对照、I级和II级肿瘤）进行各种排列组合时，均观察到显著（p<0.04 - 0.0001）差异。Wnt信号通路可能在阴茎鳞状细胞癌中发挥重要作用，Wnt信号网络中的蛋白可能是疾病诊断和预后分层的有用靶点。
