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High Expression of Sonic Hedgehog Signaling Proteins Is Related to the Favorable Outcome, EGFR Mutation, and Lepidic Predominant Subtype in Primary Lung Adenocarcinoma

  • Translational Research and Biomarkers
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Annals of Surgical Oncology Aims and scope Submit manuscript

An Erratum to this article was published on 13 June 2013

Abstract

Background

Dysregulation of the Sonic hedgehog (SHH) signaling pathway has been identified in many human malignancies. However, it remains unclear whether this pathway is activated in human lung adenocarcinoma.

Methods

We investigated the expression of the SHH ligand and its downstream molecules, such as glioma-associated oncogene homologue (GLI)-1, GLI-2, GLI-3, and ATP-binding cassette G2 (ABCG2), in 166 cases of surgically resected lung adenocarcinoma by immunohistochemistry. Correlations between the expression of SHH-related proteins and clinicopathologic parameters, histologic subtypes, and prognostic significance were statistically analyzed.

Results

SHH was highly expressed in the 36.1 % (60/166), GLI-1, GLI-2, and ABCG2 were found in 90/164 (54.9 %), 26/166 (15.7 %), and 139/165 (84.2 %), respectively, and GLI-3 was positive in all cases. SHH was more frequently highly expressed in nonsmokers, patients with no recurrences, lepidic predominant subtype, and with EGFR mutation (p < 0.05, respectively). The high expression of SHH and GLI-1 was related to better overall survival and progression-free survival (p < 0.05).

Conclusions

The SHH signaling pathway is frequently up-regulated in a subset of lung adenocarcinoma and is significantly associated with EGFR mutation and lepidic subtype. Although SHH signaling protein expression is not an independent prognostic marker, the expression of these proteins can predict a better prognostic outcome.

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Acknowledgment

This work was supported by a Grant of National Research foundation of Korea (2011-0025344 to JEK) and partly by a grant of Korea Healthcare Technology R&D project, Ministry of Health & Welfare, Republic of Korea (A111405 to JHC). The authors express their sincere gratitude to Dr. Sohee Oh for her great help with statistical analysis in this study.

Disclosure

The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Department of Pathology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam, 463-707, Republic of Korea

    Ji Eun Kim MD, PhD, Hyojin Kim MD, Ji-Young Choe MD, Pingli Sun MD & Jin-Haeng Chung MD, PhD

  2. Department of Thoracic and Cardiovascular Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea

    Pingli Sun MD & Sanghoon Jheon MD, PhD

Authors
  1. Ji Eun Kim MD, PhD
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  2. Hyojin Kim MD
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  3. Ji-Young Choe MD
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  4. Pingli Sun MD
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  5. Sanghoon Jheon MD, PhD
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  6. Jin-Haeng Chung MD, PhD
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Corresponding author

Correspondence to Jin-Haeng Chung MD, PhD.

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Supplementary material 1 (DOCX 17 kb)

Supplementary Fig. S1

Expression of SHH-related proteins in normal lung tissue (×200, in all figures). a SHH staining was weakly positive in normal bronchial epithelia. b Nuclear GLI-1 positivity was found in vascular endothelial cells, but alveolar epithelial cells are negative. c No GLI-2-positive cells were found. d GLI-3 was positive in bronchial epithelial cells and vascular endothelial cells. e ABCG2 positivity was found in endothelial cells (PPTX 960 kb)

Supplementary Fig. S2

Overall survival (OS) and progression-free survival (PFS) according to the expression of SHH (a, b) and GLI-1 (c, d) in patients with lung adenocarcinoma (PPTX 77 kb)

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Kim, J.E., Kim, H., Choe, JY. et al. High Expression of Sonic Hedgehog Signaling Proteins Is Related to the Favorable Outcome, EGFR Mutation, and Lepidic Predominant Subtype in Primary Lung Adenocarcinoma. Ann Surg Oncol 20 (Suppl 3), 570–576 (2013). https://doi.org/10.1245/s10434-013-3022-6

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  • DOI: https://doi.org/10.1245/s10434-013-3022-6

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