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Histopathological and molecular study for synchronous lung adenocarcinoma staging

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Abstract

The presence of multiple synchronous lung cancer with the same histopathological type for a patient is a common situation and an issue for staging. Pathological criteria exist to distinguish multiple primaries from intra-pulmonary metastases of the same tumor, but they lack standardization. We wondered how molecular analysis with a limited Next Generation Sequencing panel could bring further information for tumor staging in this setting. We analyzed 24 patients with a total of 50 tumor nodules (22 pairs, two triplets). We compared histopathological examination with molecular analysis. A total of 50 tumors were molecularly tested. Nucleoli size was associated with molecular analysis concordance (p = 0.047). The presence of lepidic component in any of the two larger tumors was associated with molecular analysis concordance (p = 0.012). For molecular analysis, the proportion of progression-free patients was at the limits of significance (p = 0.054) whereas the presence of lepidic component, architectural concordance, and the concordance of comprehensive histologic assessments was not related to progression-free survival. For two patients with a discordant TTF-1 immunohistochemistry, molecular analysis showed a different mutation. Our results show that a limited NGS panel brings supplementary data to classify synchronous lung adenocarcinoma in most patients. We show that molecular staging seems in accordance with progression-free survival. Histopathological examination alone might not be accurate enough to assess a correct staging for synchronous tumors. We also suggest that TTF-1 immunohistochemistry, for the rare discrepant cases, might be a surrogate to molecular analysis.

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Acknowledgements

The authors would like to thank Tiphanie Picot, PhD, for her help in the revised version of the manuscript.

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Authors and Affiliations

  1. Department of Pathology , University Hospital of Saint Etienne. North Hospital, Avenue Albert Raimond, 42055, Saint Etienne CEDEX 2, France

    Elsa Donfrancesco, Violaine Yvorel, François Casteillo, Marie-Laure Stachowicz, Michel Péoc’h & Fabien Forest

  2. Department of Thoracic Surgery, University Hospital of Saint Etienne. North Hospital, Avenue Albert Raimond, 42055, Saint Etienne CEDEX 2, France

    Arnaud Patoir & Olivier Tiffet

  3. Corneal Graft Biology, Engineering and Imaging Laboratory, BiiGC, EA2521, Federative Institute of Research in Sciences and Health Engineering, Faculty of Medicine, Jean Monnet University, Saint Etienne, France

    Michel Péoc’h & Fabien Forest

  4. Service d’Anatomie et Cytologie Pathologiques, CHU de Saint Etienne. Hôpital Nord, Avenue Albert Raimond, 42055, Saint Etienne CEDEX 2, France

    Fabien Forest

Authors
  1. Elsa Donfrancesco
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  2. Violaine Yvorel
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  3. François Casteillo
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  4. Marie-Laure Stachowicz
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  5. Arnaud Patoir
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  6. Olivier Tiffet
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  7. Michel Péoc’h
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  8. Fabien Forest
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Contributions

FF and DL wrote the manuscript. FF designed the study. ED, FC, VY, MLS, AP, OT, MP, and FF edited and reviewed the manuscript. FF, ED, VY, and FC analyzed the data. ED, FC, VY, MLS, AP, OT, MP, and FF collected the data. FF, VY, and FC are responsible of pathological study. ED and FF are responsible of molecular study. FF is responsible of statistical data. All authors gave final approval for publication. FF takes full responsibility for the work as a whole, including the study design, access to data, and the decision to submit and publish the manuscript.

Corresponding author

Correspondence to Fabien Forest.

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Local ethic committee approved the study (IRBN152018/CHUSTE). This study was performed according the standards of French law.

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The authors declare that they have no conflict of interest.

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Donfrancesco, E., Yvorel, V., Casteillo, F. et al. Histopathological and molecular study for synchronous lung adenocarcinoma staging. Virchows Arch 476, 835–842 (2020). https://doi.org/10.1007/s00428-019-02736-0

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  • DOI: https://doi.org/10.1007/s00428-019-02736-0

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