Comment on: EGFR Mutation in Patients with Lung Adenosquamous Cell Carcinoma

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By Yosuke Morodomi , Tatsuro Okamoto, and Yoshihiko Maehara
Kyushu University, Fukuoka, Japan

To the Editors,

We would like to thank Dr. Tamura, Dr. Kagohashi and Dr. Satoh for their valuable observations. We appreciate this opportunity to address their comments.

Our study found somatic Epidermal Growth Factor Receptor (EGFR) mutations in specimens from 21.9% of patients (7/32) with histological diagnoses of adenosquamous cell carcinoma (ADSQCC).[1] Over the same period, we detected EGFR mutations in 45.6% of adenocarcinoma (AD) patients (327/717) who were specified EGFR gene mutation status. Therefore, the EGFR mutation rate in ADSQCC was approximately half that in AD. An additional analysis showed that relapse-free survival and overall survival in ADSQCC patients with higher ratios of AD components did not significantly differ from those with lower ratios.

As Dr. Satoh mentions, examining whether both cell types of ADSCCC harbored the identical mutation will confer not only clinical importance but also biological interest in non-small cell lung cancers. Unfortunately, as we did not perform microdissection procedures during DNA extraction from these tissue samples, separate evaluation of gene status was not possible between the AD and squamous cell carcinoma (SQCC) components.

Nonetheless, we suspect that the two histologic components in ADSQCC might be morphological alterations from a genetically monoclonal origin. A recent investigation provided further profound evidence to support a monoclonal origin for this tumor.[2] Furthermore, EGFR mutations have been observed in a certain percentage of SQCC lung cancers,[3] which supports the validity of EGFR mutations in SQCC.

These findings suggest a possibility that mutated EGFR acts as a driver oncogene in the tumor initiation period, and then morphological changes to adenocarcinoma or SQCC develop in the tumor promotion period. As shown in Figure 3 in our study,1 the finding that EGFR mutations were widely dispersed in ADSQCC tumors irrespective of the proportion of adenocarcinoma also supports this possibility.


  1. Morodomi Y, Okamoto T, Takenoyama M, et al. Clinical Significance of Detecting Somatic Gene Mutations in Surgically Resected Adenosquamous Cell Carcinoma of the Lung in Japanese Patients. Ann Surg Oncol. 2015; 22:2593-2598
  2. Mather JP, Roberts PE, Pan Z, et al. Isolation of Cancer Stem Like Cells from Human Adenosquamous Carcinoma of the Lung Supports a Monoclonal Origin from a Multipotential Tissue Stem Cell. Fields AP, ed. PLoS ONE. 2013;8(12):e79456.
  3. Perez-Moreno P, Brambilla E, Thomas R, Soria J-C. Squamous cell carcinoma of the lung: molecular subtypes and therapeutic opportunities. Clin Cancer Res. 2012;18(9):2443–2451.

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