Id1 and Id3 co-expression correlates with clinical outcome in stage III-N2 non-small cell lung cancer patients treated with definitive chemoradiotherapy

Eduardo Castañon,Leire Arbea,Marta Moreno,Inés López,Joaquim Bosch-Barrera,José María López-Picazo,Ignacio Gil-Bazo,Víctor Collado,María Dolores Lozano,Alfonso Calvo

doi:10.1186/1479-5876-11-13

Eduardo Castañon, Leire Arbea + Show 8 more

Open Access

https://doi.org/10.1186/1479-5876-11-13

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Abstract

BackgroundInhibitor of DNA binding 1 (Id1) and 3 (Id3) genes have been related with the inhibition of cell differentiation, cell growth promotion and tumor metastasis. Recently, Id1 has been identified as an independent prognostic factor in patients with lung adenocarcinoma, regardless of the stage. Furthermore, Id1 may confer resistance to treatment (both, radiotherapy and chemotherapy).MethodsWe have studied, using monoclonal antibodies for immunohistochemistry, the Id1 and Id3 tumor epithelial expression in 17 patients with stage III-N2 non-small cell lung cancer (NSCLC) treated with definitive chemoradiotherapy.ResultsId1 expression is observed in 82.4% of the tumors, whereas Id3 expression is present in 41.2% of the samples. Interestingly, Id1 and Id3 expression are mutually correlated (R = 0.579, p = 0.015). In a subgroup analysis of patients with the most locally advanced disease (T4N2 stage), co-expression of Id1 and Id3 showed to be related with a worse overall survival (45 vs 6 months, p = 0.002). A trend towards significance for a worse progression free survival (30 vs 1 months, p = 0.219) and a lower response rate to the treatment (RR = 50% vs 87.5%, p = 0.07) were also observed.ConclusionsA correlation between Id1 and Id3 protein expression is observed. Id1 and Id3 co-expression seems associated with a poor clinical outcome in patients with locally advanced NSCLC treated with definitive chemoradiotherapy.

Highlights

Inhibitor of DNA binding 1 (Id1) and 3 (Id3) genes have been related with the inhibition of cell differentiation, cell growth promotion and tumor metastasis
We have studied the potential prognostic and predictive role of Id1 and Id3 expression by immunohistochemistry in stage III-N2 patients treated with definitive chemoradiotherapy
The tumor epithelial expression and H-score of Id1 and Id3 of these patients is detailed in table 2

Summary

Introduction

Inhibitor of DNA binding 1 (Id1) and 3 (Id3) genes have been related with the inhibition of cell differentiation, cell growth promotion and tumor metastasis. For patients with unresectable or inoperable stage III disease, the combination of platinum-based chemotherapy and radiotherapy has been considered the standard treatment with a 5-year survival rate of 20-30% in different studies [2,3]. The poor clinical outcome in this subset of NSCLC patients urges the identification of specific biomarkers able to predict survival, as a priority goal in lung cancer translational research. The availability of those prognostic and predictive factors may help to identify patients who would most likely benefit from the different treatment modalities available [5]. The characterization of novel potential molecular targets may aid to design new personalized therapies in the different subgroups of patients identified

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