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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 3/2013

01-12-2013 | Translational Research and Biomarkers

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

Authors: Ji Eun Kim, MD, PhD, Hyojin Kim, MD, Ji-Young Choe, MD, Pingli Sun, MD, Sanghoon Jheon, MD, PhD, Jin-Haeng Chung, MD, PhD

Published in: Annals of Surgical Oncology | Special Issue 3/2013

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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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Metadata
Title
High Expression of Sonic Hedgehog Signaling Proteins Is Related to the Favorable Outcome, EGFR Mutation, and Lepidic Predominant Subtype in Primary Lung Adenocarcinoma
Authors
Ji Eun Kim, MD, PhD
Hyojin Kim, MD
Ji-Young Choe, MD
Pingli Sun, MD
Sanghoon Jheon, MD, PhD
Jin-Haeng Chung, MD, PhD
Publication date
01-12-2013
Publisher
Springer US
Published in
Annals of Surgical Oncology / Issue Special Issue 3/2013
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-013-3022-6

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