Arai Kazumori, Iwasaki Tomohiro, Tsuchiya Chinatsu, Sonoda Akihiro
Department of Pathology, Shizuoka General Hospital, 4-27-1 Kitaando, Aoi-ku, Shizuoka 420-0881, Japan.
Department of Clinical Research, Shizuoka General Hospital, Japan.
Case Rep Oncol Med. 2020 May 18;2020:2492636. doi: 10.1155/2020/2492636. eCollection 2020.
Spread through air spaces (STAS) is a unique form of lung cancer progression associated with a worse prognosis. However, the mechanisms underlying STAS and the associated proteins remain unclear. Annexin A2 (ANX A2), which is a membrane-binding protein involved in cell adhesion, is known to promote cancer invasion. In this report, we describe the immunohistochemical analysis of ANX A2 expression in an invasive mucinous adenocarcinoma (IMAC) resected from a 63-year-old man in whom the tumor cells had detached from the alveolar wall and exhibited STAS. At the detachment site, we observed cytoplasmic ANX A2 positivity on the basal side and in the exfoliative gap, as well as reduced collagen IV positivity expression. This biomarker pattern suggested an IMAC with gastric lineage. We hypothesize that ANX A2 is secreted from the basal sides of tumor cells and induces tumor cell detachment by degrading the basement membrane. A further comparison of this case with an IMAC with nongastric lineage suggested the following probabilities: (1) ANX A2 likely contributes to STAS in a manner that is dependent on its subcellular localization. (2) Both the subcellular localization of ANX A2 and the detachment site depend on tumor cell characteristics, including the biomarker immunophenotype.
气腔播散（STAS）是一种独特的肺癌进展形式，与较差的预后相关。然而，STAS的潜在机制及相关蛋白仍不清楚。膜联蛋白A2（ANX A2）是一种参与细胞黏附的膜结合蛋白，已知其可促进癌症侵袭。在本报告中，我们描述了对一名63岁男性切除的浸润性黏液腺癌（IMAC）中ANX A2表达的免疫组化分析，该患者的肿瘤细胞已从肺泡壁脱离并表现出气腔播散。在脱离部位，我们观察到基底侧和剥脱间隙的细胞质ANX A2呈阳性，以及IV型胶原阳性表达降低。这种生物标志物模式提示为具有胃源性的IMAC。我们推测ANX A2从肿瘤细胞基底侧分泌，并通过降解基底膜诱导肿瘤细胞脱离。将该病例与非胃源性IMAC进行进一步比较，提示以下可能性：（1）ANX A2可能以依赖其亚细胞定位的方式促进气腔播散。（2）ANX A2的亚细胞定位和脱离部位均取决于肿瘤细胞特征，包括生物标志物免疫表型。
