Annexin A2 Expression in the Aerogenous Spread of PulmonaryInvasive Mucinous Adenocarcinoma with Gastric Lineage

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 theimmunohistochemical analysis of ANX A2 expression in an invasive mucinous adenocarcinoma (IMAC) resected from a63-year-old man in whom the tumor cells had detached from the alveolar wall and exhibited STAS. At the detachmentsite, we observed cytoplasmic ANX A2 positivity on the basal side and in the exfoliative gap, as well as reduced collagen IVpositivity expression. This biomarker pattern suggested an IMAC with gastric lineage. We hypothesize that ANX A2 is secretedfrom the basal sides of tumor cells and induces tumor cell detachment by degrading the basement membrane. A furthercomparison of this case with an IMAC with nongastric lineage suggested the following probabilities: (1) ANX A2 likelycontributes to STAS in a manner that is dependent on its subcellular localization. (2) Both the subcellular localization of ANXA2 and the detachment site depend on tumor cell characteristics, including the biomarker immunophenotype.