Pathology Department, Tel HaShomer Hospital, Tel Hashomer, Israel.
Thoracic Oncology Unit, Institute of Oncology, Tel HaShomer Hospital, Tel Hashomer, Israel.
J Clin Pathol. 2020 Oct;73(10):636-641. doi: 10.1136/jclinpath-2019-206420. Epub 2020 Feb 14.
To analyse microRNA (miR)-21 distribution and expression at the cellular level in non-small cell lung cancer (NSCLC). MiR-21 is an oncogenic microRNA overexpressed in NSCLC. In previous studies, overexpression of miR-21 was evaluated from the tumour bulk by quantitative reverse transcription PCR with results expressed on average across the entire cell population.
We used in situ hybridisation and immunohistochemistry to assess the correlation between miR-21 levels and the expression of markers that may be possible targets (epidermal growth factor reaction) or may be involved in its upregulation (phosphatase and tensin homolog (PTEN), p53). The Pearson's χ tests was used to assess correlation with clinicopathological data and with miR-21 expression both in tumour and tumour stroma.
Cytoplasmic staining and expression of Mir-21 were detected in the tumours and in associated stromal cells. Expression was highest in the stroma immediately surrounding the tumour cells and decreased as the distance from the tumour increased. No expression of miR-21 was found in normal lung parenchyma and a significant association was found between tumour localised miR-21 and PTEN.
Presence of miR-21 in both cell tumour and stromal compartments of NSCLC and the relationship with PTEN confirms miR-21 as a microenvironment signalling molecule, possibly inducing epithelial mesenchymal transition and invasion by targeting PTEN in the stromal compartment possibly through exosomal transport. In situ immunohistochemical studies such as ours may help shed light on the complex interactions between miRNAs and its role in NSCLC biology.
分析非小细胞肺癌（NSCLC）细胞水平的 microRNA（miR）-21 分布和表达。miR-21 是一种在 NSCLC 中过表达的致癌 microRNA。在之前的研究中，通过定量逆转录 PCR 从肿瘤块中评估了 miR-21 的过表达，结果以整个细胞群体的平均值表示。
我们使用原位杂交和免疫组织化学来评估 miR-21 水平与可能的靶标（表皮生长因子反应）的表达或可能参与其上调的标志物（磷酸酶和张力蛋白同源物（PTEN），p53）之间的相关性。Pearson χ 检验用于评估与临床病理数据以及肿瘤和肿瘤基质中 miR-21 表达的相关性。
在肿瘤和相关基质细胞中检测到细胞质染色和 Mir-21 的表达。表达在肿瘤细胞周围的基质中最高，随着与肿瘤的距离增加而降低。在正常肺实质中未发现 miR-21 的表达，并且肿瘤局部 miR-21 与 PTEN 之间存在显著相关性。
NSCLC 中肿瘤细胞和基质细胞中都存在 miR-21，以及与 PTEN 的关系证实了 miR-21 作为微环境信号分子的作用，可能通过靶向基质中的 PTEN 诱导上皮间质转化和侵袭，可能通过外泌体运输。像我们这样的原位免疫组织化学研究可能有助于阐明 miRNAs 及其在 NSCLC 生物学中的作用之间的复杂相互作用。
