The stem cell gene “inhibitor of differentiation 1” (ID1) is frequently expressed in non-small cell lung cancer

Rothschild, Sacha I.; Kappeler, Andreas; Ratschiller, Daniel; Betticher, Daniel C.; Tschan, Mario P.; Gugger, Mathias; Gautschi, Oliver

doi:10.1016/j.lungcan.2010.06.018

« Previous Next »Lung Cancer
Volume 71, Issue 3 , Pages 306-311, March 2011

The stem cell gene “inhibitor of differentiation 1” (ID1) is frequently expressed in non-small cell lung cancer☆

Sacha I. Rothschild
- University of Bern, Department Clinical Research, 3010 Bern, Switzerland
- University Hospital Bern, Department of Medical Oncology, 3010 Bern, Switzerland
Andreas Kappeler
- University of Bern, Institute of Pathology, Murtenstrasse 31, 3010 Bern, Switzerland
Daniel Ratschiller
- University Hospital Bern, Department of Medical Oncology, 3010 Bern, Switzerland
Daniel C. Betticher
- Hospital of Fribourg, Clinic of Medical Oncology, 1700 Fribourg, Switzerland
Mario P. Tschan
- University of Bern, Department Clinical Research, 3010 Bern, Switzerland
- University Hospital Bern, Department of Medical Oncology, 3010 Bern, Switzerland
Mathias Gugger
- University of Bern, Institute of Pathology, Murtenstrasse 31, 3010 Bern, Switzerland
- Both authors contributed equally.
- Corresponding author. Tel.: +41 31 632 99 30; fax: +41 31 632 99 38.
Oliver Gautschi
- University of Bern, Department Clinical Research, 3010 Bern, Switzerland
- University Hospital Bern, Department of Medical Oncology, 3010 Bern, Switzerland
- Both authors contributed equally.

Received 3 May 2010; received in revised form 21 June 2010; accepted 28 June 2010. published online 16 August 2010.

Abstract

Aims

Inhibitor of differentiation 1 (ID1) plays a role in cellular differentiation, proliferation, angiogenesis and tumor invasion. As shown recently, ID1 is positively regulated by the tyrosine kinase SRC in lung carcinoma cell lines and with that appears as a potential new therapeutic target in non-small cell carcinoma (NSCLC). To substantiate this hypothesis we examined ID1, SRC and matrix metalloproteinase-9 (MMP-9) immunohistochemically in human NSCLC specimens.

Methods

From 61 consecutive patient tissue samples of a tumor tissue bank a one core tissue microarray (TMA) was produced and whole slide tissue samples of preinvasive lesions used. The staining of commercial antibodies was assessed by the H-score. Statistical analyses based on Spearman's rank correlation coefficient.

Results

ID1 was expressed in the nucleus in 70% of squamous cell carcinomas and 50% of non-squamous cell carcinomas and in vascular endothelium of non-tumor tissue. Cytoplasmic staining was found in all samples for SRC and in 93% for MMP-9. ID1-positive tissue samples co-expressed SRC and MMP-9 in 94%. In non-squamous cell carcinomas, H-scores of ID1 and SRC correlated with each other (p=0.04). H-score of MMP-9 correlated with tumor grade (p=0.04). The carcinoma findings were reflected in preinvasive lesions.

Conclusions

We describe for the first time the immunohistochemical expression of ID1 in the majority of NSCLC samples. The almost general co-expression of ID1, SRC and MMP-9 supports their cooperation in vivo and warrants further investigation of ID1 as a therapeutic target.

Keywords: Inhibitor of differentiation protein 1, SRC, MMP-9, Non-small cell lung cancer, Immunohistochemistry