Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
University Hospital Bezanijska Kosa, Belgrade, Serbia.
PeerJ. 2022 Mar 9;10:e13055. doi: 10.7717/peerj.13055. eCollection 2022.
Connexins are transmembrane proteins forming gap junctions between the cells, which allow intercellular communication. Significance of gap junctions and connexins in lung carcinoma is not yet understood. The objective of the study was to investigate immunohistochemical expression and the localization of connexin-43 (Cx43) in primary lung carcinoma and its lymphatic metastases.
Surgical specimens of excised tumors from 88 patients (45 men and 43 women, 61.9 ± 7.4 years) with lung carcinoma (52 adenocarcinoma (AC), 36 squamous cell carcinoma (SqCC)) who were operated on at the University Hospital "Bezanijska Kosa" in a five-year period (2012-2016) were used. We conducted immunohistochemical staining for Cx43 and measured the degree of expression (percentage of positive cells and staining intensity) as well as localization of Cx43 in primary tumor and in lymphatic metastases.
Immunohistochemical analysis of the primary tumors revealed that SqCC showed significantly higher percentage of tumor cells expressing Cx43 as well as higher staining intensity than AC ( < 0.001). Almost 70% of samples with SqCC showed high Cx43 expression, whereas AC showed no expression in more than 50% of cases. Localization of Cx43 expression was most often cytoplasmic (AC and SqCC) and combined membranous and cytoplasmic (SqCC) with very rare instances of nuclear localization (AC). Almost the same pattern in distribution, intensity, and localization of Cx43 expression was observed in the lymph node metastases; however, almost a third of AC cases changed the pattern of Cx43 expression in the metastasis compared to primary tumor.
The results of this study showed that lung carcinomas express Cx43 in more than 65% of cases and that it was aberrantly localized (not membranous localization). We highlighted that SqCC expressed Cx43 more than did AC, both in primary tumor and lymphatic metastases. Further research is needed to establish whether Cx43 could be used as a prognostic biomarker in lung carcinoma.
连接蛋白是形成细胞间缝隙连接的跨膜蛋白，允许细胞间通讯。缝隙连接和连接蛋白在肺癌中的意义尚不清楚。本研究的目的是研究细胞连接蛋白-43（Cx43）在原发性肺癌及其淋巴转移中的免疫组织化学表达和定位。
使用了 88 名（45 名男性和 43 名女性，61.9±7.4 岁）在五年期间（2012-2016 年）于贝尔格莱德大学医院“Bezanijska Kosa”接受手术切除肿瘤的原发性肺癌患者（52 例腺癌（AC），36 例鳞状细胞癌（SqCC））的手术标本。我们对 Cx43 进行了免疫组织化学染色，并测量了原发性肿瘤和淋巴转移中 Cx43 的表达程度（阳性细胞百分比和染色强度）以及定位。
对原发性肿瘤的免疫组织化学分析表明，SqCC 显示出明显更高比例的肿瘤细胞表达 Cx43 以及更高的染色强度，而 AC 则没有（<0.001）。几乎 70%的 SqCC 样本显示 Cx43 高表达，而 AC 则超过 50%的病例没有表达。Cx43 表达的定位最常见于细胞质（AC 和 SqCC）和膜细胞质混合（SqCC），很少有核定位（AC）。在淋巴结转移中观察到几乎相同的 Cx43 表达分布、强度和定位模式；然而，与原发性肿瘤相比，几乎三分之一的 AC 病例在转移中改变了 Cx43 表达模式。
本研究结果表明，超过 65%的肺癌病例表达 Cx43，且其定位异常（不是膜定位）。我们强调，SqCC 在原发性肿瘤和淋巴转移中比 AC 更表达 Cx43。需要进一步研究以确定 Cx43 是否可作为肺癌的预后生物标志物。
