Application of the Novel Grading System of Invasive Pulmonary Adenocarcinoma in a Real Diagnostic Scenario: A Brief Report of 9353 Cases

Introduction: The International Association for the Study of Lung Cancer proposed a novel grading system of invasive pulmonary adenocarcinoma (IPA), but the application of this grading system and its genotypic characterization in the real diagnostic scenario has never been reported. Methods: We prospectively collected and analyzed the clinicopathological and genotypic features of a cohort of 9353 consecutive patients with resected IPA, including 7134 patients with detection of common driver mutation. Results: In the entire cohort, 3 (0.3%) of lepidic, 1207 (19.0%) of acinar, and 126 (23.6%) of papillary predominant IPAs were diagnosed as grade 3. In chronological order, an evident downtrend of the proportion of grade 2 was observed in chronological order. Conversely, the diagnostic ratio of grade 1 (8.0%-14.5%) and grade 3 (27.9%-32.3%) experienced a gradual rise. EGFR mutation was more frequently detected in grade 2 (77.5%) and grade 1 (69.7%) IPA than grade 3 (53.7%, p < 0.001), whereas the mutation rates of KRAS, BRAF, ALK, and ROS1 were higher in grade 3 IPA. More importantly, the rate of EGFR mutation gradually fell as the proportion of high-grade components increased, to 24.3% in IPA with more than 90% high-grade components. Conclusions: The grading system for IPA could be applied to stratify patients with different clinicopathological and genotypic features in a real diagnostic scenario. (c) 2023 The Authors. Published by Elsevier Inc. on behalf of the International Association for the Study of Lung Cancer. This is an open access article under the CC BY-NC-ND li-cense (http://creativecommons.org/licenses/by-nc-nd/ 4.0/).