Hans Blaauwgeers

143 Editorial (PRO/) CON: is STAS an inducible artifact? remained present220 a feature fitting more with radial non-invasive growth as seen in lepidic featuring adenocarcinoma of either precursor or outgrowth type. STAS and prognosis Since STAS was included in the WHO classification of 2015, close to 200 manuscripts have been published on this subject. Many of them show a significant association with recurrence free and overall survival. Not surprisingly, STAS is significantly associated with many of the known adverse prognostic factors: tumour size117 227 143 133 228 229 230 231 232 233 234 235 236 237 238, lymph node metastases236 239 240 241, lymphovascular invasion, vascular invasion133 228 229 232 234 235 236 242 134 243 244 245 246 247, micropapillary and solid adenocarcinoma growth patterns228 235 248 249 250 251. This is not surprising if STAS, whether biological or artefactual, reflects poorly differentiated adenocarcinoma with easy decohesion of tumour cells, likely because of reduced intercellular adhesion. Importantly, STAS was in an extensive study about grading in 3 independent cohorts in comparison with other histological parameters NOT selected as relevant parameter for the IASLC grading system252. This substantially weakens the application prospect of STAS as prognostic factor. In summary, there is no incontrovertible evidence that STAS as currently presented, is indeed a biological phenomenon and not rather an inducible artifact with inconsistency in sampling. On top of this, the reproducibility of its presence is at best moderate. Inclusion of STAS in the WHO classification as an established and widely agreed-upon phenomenon is premature173. STAS, including the underlying biology of dissociation, need further investigation. 11

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