138 Chapter 11 patients and was considered an additional argument for its cause by manipulation during surgery219. In short, the unwelcome possibility and understandable concern exist that tumourcell release during surgery contributes to metastatic colonization207. At least some force is executed during manipulation by the surgeon. Pathological aspects of STAS In the proposed STAS concept it is argued that STAS tumour cells can attach to the alveolar walls rather than appearing free floating, as seen on the two-dimensional sections, thus suggesting that tumour cells detach from the main tumour, migrate through air (= alveolar) spaces, and reattach to the alveolar walls through vessel cooption, allowing them to survive and grow220. The main question is if the provided arguments are persuasive enough to definitively accept STAS as a biological property related to tumour growth and invasion. The argument of 3-dimensional analysis and loose tumour cells In 2012 Onozato and colleagues reported a 3-dimensional analysis of four adenocarcinoma resection specimens, and in two cases they found islands of tumour cells being detached in alveolar spaces that had not been described in any of the existing adenocarcinoma classifications132. In serial sections islands of tumour cells extended into a deeper area of the tissue and were interconnected with each other and the main tumour with a solid pattern that was surrounded by the islands. In other words, they found seemingly detached tumour cells localized at some distance from the main tumour, which were connected to the main tumour in a tentacular way. In a subsequent study they extended the number of analysed cases with a mainly 3-dimensional approach and reported a prognostic relevance to this finding115. Yagi and colleagues performed 3-dimensional image analysis of serial sections from 4 archived formalin and paraffin embedded samples by using different stains: haematoxylin and eosin (H&E), immunohistochemistry (IHC), and immunofluorescence (IF) staining220. These sections were cut from retrospectively collected specimen with iatrogenic collapsed tissue. Although the results section mentioned “the STAS cells are focally in close apposition to the pre-existing capillaries in the alveolar septa”, in the accompanying figure the text is extended with the interpretation“ (i) attached to the alveolar wall, (ii) replacing the normal pneumocytes” as well as “attached to and (iii) penetrating the alveolar wall”. Actually, at least one of the reasons that the 3-dimensional study was performed was related to the question how these loose tumour cells get their energy, while seemingly free floating in the air space. The authors argue that focally there is a close approximation of some cells with the pre-existing alveolar wall and they applied for this observation the biological term ‘vessel co-option’. Vessel co-option was previously defined as incorporation of pre-existing vessels from surrounding tissue by cancer cells as opposed to generating new vessels (= angiogenesis)114 221. Remarkably, the lack
RkJQdWJsaXNoZXIy MTk4NDMw