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Squamous Cell Carcinoma Related Oncogene Regulates Angiogenesis through Vascular Endothelial Growth Factor-A

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Abstract

Background

Squamous cell carcinoma related oncogene expression (SCCRO) correlates with vascular endothelial growth factor-A expression. This data is validated in human lung tumors and provides a putative pathway for angiogenesis in a subset of squamous cell carcinomas. Squamous cell carcinoma related oncogene is a novel oncogene identified by positional cloning of a recurrent amplification at 3q26.3. It is over-expressed in 39.8% of lung, head and neck, cervical, and ovarian carcinomas. SCCRO imparts an aggressive phenotype to affected cancers, which may be related to increased angiogenesis due to SCCRO expression. Our previous work has demonstrated a link between SCCRO and vascular endothelial growth factor-A (VEGF-A) expression in vitro, suggesting a mechanism for SCCRO-induced angiogenesis. The present study aims to confirm and validate this link between SCCRO and VEGF-A expression in an ex vivo human tumor cohort.

Methods

Fresh tissue was collected at Memorial Sloan-Kettering Cancer Center from 34 patients undergoing primary resection of lung squamous cell carcinomas. RNA was extracted from this tissue, reverse-transcribed, and real-time polymerase chain reaction (RT-PCR) was carried out using a BioRad iQ iCycler with SYBR green fluorophore. Microvessel counting was performed on the tumor specimens using CD34 immunohistochemistry.

Results

The expression of both SCCRO and VEGF-A mRNA varies widely in both tumor and normal tissue. SCCRO and VEGF-A co-expression was significantly correlated (R2 = 0.63; P < 0.032). Microvessel counts were not associated with expression of SCCRO or VEGF-A and failed to significantly predict survival. VEGF-A expression in this patient group is a predictor of overall survival (P < 0.032).

Conclusions

VEGF-A expression correlates with SCCRO expression in these primary human lung squamous cell carcinomas and is a predictor of clinical behavior. This data supports the association of SCRRO and VEGF-A in the induction of angiogenesis.

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Authors and Affiliations

  1. Laboratory of Epithelial Cancer, Biology, and Head and Neck Service (SGT, PO-c, PR, IN, CNC, BS), Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York

    Simon G. Talbot MD, Pornchai O-charoenrat MD, PhD, Pabbathi Reddy PhD, Ivan Ngai BS, Christina N. Cordeiro, Richard J. Wong MD & Bhuvanesh Singh MD

  2. Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York

    Ronald Ghossein MD

  3. Division of Thoracic Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York

    Mark G. Kris MD

  4. Division of Thoracic Surgery, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York

    Inderpal S. Sarkaria MD & Valerie W. Rusch MD

  5. Head and Neck Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY, 10021

    Bhuvanesh Singh MD

Authors
  1. Simon G. Talbot MD
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  2. Pornchai O-charoenrat MD, PhD
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  3. Inderpal S. Sarkaria MD
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  4. Ronald Ghossein MD
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  5. Pabbathi Reddy PhD
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  6. Ivan Ngai BS
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  7. Christina N. Cordeiro
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  8. Richard J. Wong MD
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  11. Bhuvanesh Singh MD
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Correspondence to Bhuvanesh Singh MD.

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Talbot, S.G., O-charoenrat, P., Sarkaria, I.S. et al. Squamous Cell Carcinoma Related Oncogene Regulates Angiogenesis through Vascular Endothelial Growth Factor-A. Ann Surg Oncol 11, 530–534 (2004). https://doi.org/10.1245/ASO.2004.03.014

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  • DOI: https://doi.org/10.1245/ASO.2004.03.014

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