Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
Universitat Autònoma de Barcelona, Barcelona, Spain.
J Eur Acad Dermatol Venereol. 2018 Apr;32(4):581-586. doi: 10.1111/jdv.14514. Epub 2017 Oct 5.
Every actinic keratosis (AK) starts with atypia at the basal layers of the epidermis (AK I). Progression into invasive squamous cell carcinoma (iSCC) may occur following two main pathways, classical and differentiated. In the former, iSCC only occurs after involvement of the upper epidermal layers by atypical cells (AK III), while in the latter iSCC develops directly from AK I. In the anogenital mucosa, these two pathways are associated with differential expression of p53 and p16.
To explore differences between both pathways in the pathogenesis of AK, focusing on Ki67, p53, p16 and molecules that reveal epithelial-mesenchymal transition (EMT).
Tissue microarrays representative of superficial and deep portions of 80 consecutive iSCCs (53 DP/27CP) were studied immunohistochemically using antibodies against Ki67, p53, p16, vimentin, E-cadherin, β-catenin and D2-40. The evaluation was performed by three researchers and the results compared to consensus.
Invasive squamous cell carcinomas originated through the differentiated pathway exhibited significantly lower proliferative activity (Ki67) (30% vs 46%, P = 0.003) and significantly lower expression of vimentin (P < 0.001), E-cadherin (P < 0.001) and membranous β-catenin (P < 0.001) than iSCCs developed through the classical pathway. The expression of E-cadherin and membranous β-catenin was significantly correlated (Pearson's r = 0.386, Spearman's Rho < 0.001). There were no significant differences regarding the expressions of p53, p16 and D2-40.
Epithelial-mesenchymal transition participates in transformation from AK I into iSCC (differentiated pathway), whereas a higher proliferative capacity facilitates intraepidermal extension in the classical pathway. Podoplanin, which is also involved in tumour invasion, does not seem to play a differential role in either pathway. Finally, the absence of differences in p53 and p16 expressions is at variance with other epithelia where the classical pathway is associated with human papillomavirus infection and can be explained by the fact that both AK pathways share identical mechanisms of actinic oncogenesis.
每一例光化性角化病（AK）均起始于表皮基底层的异型增生（AK I）。侵袭性鳞状细胞癌（iSCC）可通过两条主要途径发展，即经典途径和分化途径。在前一种途径中，只有当异常细胞累及表皮上层时才会发生 iSCC（AK III），而后一种途径中 iSCC 则直接从 AK I 发展而来。在肛门生殖器黏膜中，这两条途径与 p53 和 p16 的差异表达相关。
探讨 AK 发病机制中两条途径的差异，重点关注 Ki67、p53、p16 以及揭示上皮-间充质转化（EMT）的分子。
使用针对 Ki67、p53、p16、波形蛋白、E-钙黏蛋白、β-连环蛋白和 D2-40 的抗体，对 80 例连续的 iSCC（53 例 DP/27 例 CP）的组织微阵列进行免疫组织化学研究。由三位研究人员进行评估，并与共识结果进行比较。
通过分化途径起源的侵袭性鳞状细胞癌表现出显著更低的增殖活性（Ki67）（30%对 46%，P=0.003）和显著更低的波形蛋白（P<0.001）、E-钙黏蛋白（P<0.001）和膜性β-连环蛋白（P<0.001）表达，而通过经典途径发展的 iSCC 则不然。E-钙黏蛋白和膜性β-连环蛋白的表达显著相关（Pearson r=0.386，Spearman Rho<0.001）。p53、p16 和 D2-40 的表达无显著差异。
上皮-间充质转化参与 AK I 向 iSCC（分化途径）的转化，而较高的增殖能力有利于经典途径中的表皮内延伸。同样参与肿瘤侵袭的 podoplanin 在两条途径中似乎没有发挥差异作用。最后，p53 和 p16 表达的差异缺失与其他上皮组织不同，在这些上皮组织中，经典途径与人类乳头瘤病毒感染相关，这可以用 AK 两条途径均具有相同的光化致癌发生机制来解释。
