Reply to Mizuno: implication of mutation profile of resected lung adenocarcinoma

We read with a great interest the Editorial by Mizuno and Sakao (1), and we thank the authors for their interest in our work (2) as well as for their kind comments.

Indeed, the interest to primary lung adenocarcinoma, its mutation profile and the lymph-nodal involvement’s prognostic role has never been as strong as in the last few years.

Definitively, we agree with Mizuno about the paucity of knowledge on appearance of mediastinal lymph-nodal involvement without hilar one (skip-N2 metastasis) in non-small cell lung cancer (NSCLC). The role of tumor-containing lobe, tumor location and possible visceral pleura invasion remain a matter of interest.

In this contest, our study takes into light a possible correlation between EGFR mutation presence and skip-N2 lymphatic spread. On the other hand, no correlation between skip-N2 and KRAS mutation was observed. As reported, the results of our study were revealed in a population characterized by (I) a lower incidence of skip-N2 metastasis than the majority of rates reported in literature (3-6); (II) a lower rate of EGFR mutations than in similar studies conducted in Asian population (3).

As the authors mentioned, these findings could rise interest in mutation profile investigation in still unexplored contest. Indeed, the possible impact of EGFR mutations on the mechanisms underlying the skip N2 pathway of lymph nodal metastasis is also unclear. We believe that this study could represent a first prompt in this field of translational research.

Due to the small population, our study did not analyze impact of different EGFR exon mutations and KRAS amino-acid substitutions on skip-N2 nodal involvement and prognosis. Moreover, effect of different complementary treatment (e.g., chemotherapy, radiotherapy, biological therapy and immunotherapy) according to skip-N2 metastases and different mutation profiles were unexplored and probably needs a prospective setting.

In conclusion, we hope that our results support future study and translation research on mutation profile of surgically resected adenocarcinoma of the lung.

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned and reviewed by the Section Editor Dr. Qiang Pu (Video-Assisted Thoracic Surgery, Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/vats.2017.08.02). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are 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.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Mizuno T, Sakao Y. Does oncogenic mutation status influence tumor spread in resectable lung cancer? Video-assist Thorac Surg 2017;2:41. [Crossref]
2. Guerrera F, Renaud S, Tabbó F, et al. Epidermal growth factor receptor mutations are linked to skip N2 lymph node metastasis in resected non-small-cell lung cancer adenocarcinomas. Eur J Cardiothorac Surg 2017;51:680-8. [Crossref] [PubMed]
3. Riquet M, Assouad J, Bagan P, et al. Skip mediastinal lymph node metastasis and lung cancer: a particular N2 subgroup with a better prognosis. Ann Thorac Surg 2005;79:225-33. [Crossref] [PubMed]
4. Li H, Hu H, Wang R, et al. Lung adenocarcinoma: Are skip N2 metastases different from non-skip? J Thorac Cardiovasc Surg 2015;150:790-5. [Crossref] [PubMed]
5. Benoit L, Anusca A, Ortega-Deballon P, et al. Analysis of risk factors for skip lymphatic metastasis and their prognostic value in operated N2 non-small-cell lung carcinoma. Eur J Surg Oncol 2006;32:583-7. [Crossref] [PubMed]
6. Ilic N, Petricevic A, Arar D, et al. Skip mediastinal nodal metastases in the IIIa/N2 non-small cell lung cancer. J Thorac Oncol 2007;2:1018-21. [Crossref] [PubMed]