The more the micropapillary pattern in stage I lung adenocarcinoma, the worse the prognosis—a retrospective study on digitalized slides
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Although the majority of lung adenocarcinomas show mixed pattern, only the predominant component is taken into account according to the novel classification. We evaluated the proportion of different patterns and their impact on overall survival (OS) and disease-free survival (DFS). Patterns were recorded according to predominance and their proportions were rated and calculated by objective area measuring on digitalized, annotated slides of resected stage I lung adenocarcinomas. Spearman’s rank correlation, Kaplan-Meier models and the log rank test were used for statistical evaluation. Two hundred forty-three stage I adenocarcinoma were included. Lepidic pattern is more frequent in tumours without recurrence (20 vs. 8%), and lepidic predominant tumours have favourable prognosis (OS 90.5%, DFS 89.4%), but proportions above 25% are not associated with improving outcome. Solid and micropapillary patterns are more frequent in patients with recurrence (48 vs. 5% and 13 vs. 4%) and predominance of each one is associated with unfavourable prognosis (OS 64.1%, DFS 56.3% and OS 28.1%, DFS 28.1%, respectively). Above 25%, a growing proportion of solid or micropapillary pattern is not associated with worsening prognosis. In contrast, tumours having micropapillary pattern as secondly predominant form a different intermediate group (OS 51.1%, DFS 57.8%). Our study was based on measured area of each growth pattern on all available slides digitalized. This is the most precise way of determining the size of each component from the material available. We propose using predominant and secondly predominant patterns for prognostic purposes, particularly in tumours having solid or micropapillary patterns.
KeywordsLung adenocarcinoma Growth pattern Predominant Second predominant component Survival
We gratefully acknowledge the assistance of Dániel Urbán, Réka Némedi, Zsófia Tornyossy and Noémi Tóth in collecting clinical data of the patients and in the digitalization of slides.
All authors of the manuscript made substantial contributions to the conception or design of the work; the acquisition, analysis or interpretation of data for the work; drafting the work and/or revising it critically for important intellectual content; final approval of the version submitted for publication; and agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
More specifically, author contribution is listed as follows:
TZ: Concept, case selection, application and refinement of the methods, evaluation of all cases, analysis of data, preparation of the manuscript, finalisation and approval of the manuscript
TN: Statistical analysis, preparation of the manuscript, finalisation and approval of the manuscript
LT: Case selection, application and refinement of the methods, evaluation of histology slides, finalisation and approval of the manuscript
GC: Development of the methods, supervision, preparation of the manuscript, finalisation and approval of the manuscript
RP: Data collection, finalisation and approval of the manuscript
EC: Data collection, finalisation and approval of the manuscript
TG: Resources, finalisation and approval of the manuscript
AO: Resources, finalisation and approval of the manuscript
BP: Resources, finalisation and approval of the manuscript
JF: Concept, case selection, finalisation and approval of the manuscript
This study was partially funded by the National Research, Development and Innovation Office grant GINOP-2.3.2-15-2016-00020.
Compliance with ethical standards
The authors have consulted the journal policy regarding compliance with ethical standards and state that accepted principles of ethical and professional conduct have been followed. The authors include information regarding sources of funding (previous section) and potential conflicts of interest (financial or non-financial) (next section). This retrospective study was approved by the institutional ethical committee of the Albert Szent-Györgyi Clinical Centre of the University of Szeged. The study did not include animals; therefore, issues relating to animal welfare do not apply.
Conflict of interest
The authors declare that they have no conflict of interest.
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