Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Nov;12(6):369-74.
doi: 10.1016/j.cllc.2011.02.002. Epub 2011 May 17.

Immunohistochemical overexpression of platelet-derived growth factor receptor-beta (PDGFR-β) is associated with PDGFRB gene copy number gain in sarcomatoid non-small-cell lung cancer

Anne S Tsao  1 , Wei Wei, Elisabetta Kuhn, Loreto Spencer, Luisa M Solis, Milind Suraokar, J Jack Lee, Waun Ki Hong, Ignacio I Wistuba
Affiliations

Immunohistochemical overexpression of platelet-derived growth factor receptor-beta (PDGFR-β) is associated with PDGFRB gene copy number gain in sarcomatoid non-small-cell lung cancer

Anne S Tsao et al. Clin Lung Cancer. 2011 Nov.

Abstract

Sarcomatoid non-small cell lung cancer (NSCLC) is an uncommon histologic variant that has not been molecularly well-characterized. We conducted immunohistochemical and fluorescence in situ hybridization studies of PDGF-B/PDGFR-b on archived surgically resected specimens and showed high PDGFR-b IHC expression and gene copy number gain. Further studies are warranted to determine whether PDGFR-b is a feasible therapeutic target in this population.

Introduction: Sarcomatoid non-small cell lung cancer (NSCLC) is an uncommon histologic variant that has not been molecularly well-characterized. We hypothesized that the PDGF-B/PDGF-Rβ pathway may be dysregulated in sarcomatoid lung cancer.

Methods: We conducted immunohistochemical (IHC) and gene copy number gain studies of PDGF-B/PDGFR-β on archived surgically resected specimens, 43 sarcomatoid NSCLCs and 42 control NSCLCs that were age, gender and stage-matched. Biomarkers were correlated to patient demographics, tumor characteristics, and survival.

Results: Sarcomatoid tumors had higher PDGFR-β IHC expression than control NSCLC (median score 2.69 vs. 1.93; P < 0.0001). No difference was seen between the two groups of PDGF-B IHC expression; and neither PDGF-B nor PDGFR-β IHC levels correlated with gender, age, clinical or pathologic TNM status, or overall survival. PDGFRB gene copy number was evaluated by FISH using three ways: presence of amplification, gene copy number gain, and gene copy ratio between tumor and normal tissue. PDGFRB gene copy number gain was associated with sarcomatoid histology (P = 0.006), lower clinical and pathologic T-stage (P = 0.07, P = 0.048), and higher pathologic N-stage (P = 0.013). Sarcomatoid NSCLC patients (P = 0.006) and female patients (P = 0.03) had higher gene copy ratios above 1.83. Higher PDGFR-β IHC expression in tumor cells was associated with gene copy number gain (P = 0.021) and higher gene copy ratio status (P = 0.005).

Conclusion: This is the first study to demonstrate high PDGFR-β IHC expression and gene copy number gain in sarcomatoid NSCLC tumors and suggests that further studies are warranted to determine whether PDGFR-β is a feasible therapeutic target in this population.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Representative microphotographs of two sarcomatoid lung carcinomas (A, pleomorphic subtype, and D, giant cell, hematoxilyn-eosin, H&E) with strong cytoplasmic expression of PDGF-B (B and E; black arrows) and PDGFR-β (C and F; black arrows) in highly atypical malignant cells. Tumor stromal cells and blood vessel endothelial cells show PDGFR-β IHC expression (red arrow). Magnification of ×200.
Figure 2
Figure 2
Box plots demonstrating the distribution of biomarkers by histologic subtype NSCLC versus sarcomatoid lung cancer. The white cross demonstrating the mean immunohistochemical (IHC) score and the white bar indicating the median IHC score by (A) a statistically significant difference by Wilcoxon rank sum test in PDGFRβ IHC (p<0.0001) and no significant difference in (B) PDGF-B IHC (p=0.16).
Figure 3
Figure 3
Representative microphotographs of two sarcomatoid lung carcinomas examined by FISH showing normal PDGFRB copies (A) and gene amplification (B) in malignant cells. Magnification ×1,000. Red signals (white arrows) represent PDGFRB gene copies and green signals (green arrows) represent the chromosome 5 centromeric probe. Cell nuclei stained with 4’,6-diamidino-2-phenyldole.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Brambilla E, et al. The new World Health Organization classification of lung tumours. Eur Respir J. 2001;18(6):1059–1068. - PubMed
    1. Martin LW, et al. Sarcomatoid carcinoma of the lung: a predictor of poor prognosis. Ann Thorac Surg. 2007;84(3):973–980. - PubMed
    1. Pelosi G, et al. Pleomorphic carcinomas of the lung show a selective distribution of gene products involved in cell differentiation, cell cycle control, tumor growth, and tumor cell motility: a clinicopathologic and immunohistochemical study of 31 cases. Am J Surg Pathol. 2003;27(9):1203–1215. - PubMed
    1. Veronesi G, et al. Fluoro-deoxi-glucose uptake and angiogenesis are independent biological features in lung metastases. Br J Cancer. 2002;86(9):1391–1395. - PMC - PubMed
    1. Donnem T, et al. Prognostic impact of platelet-derived growth factors in non-small cell lung cancer tumor and stromal cells. J Thorac Oncol. 2008;3(9):963–970. - PubMed

Publication types

MeSH terms

Substances