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From the 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; the Department of Pathology (RG), Memorial Sloan-Kettering Cancer Center; Division of Thoracic Oncology (MGK), Department of Medicine, Memorial Sloan-Kettering Cancer Center; Division of Thoracic Surgery (ISS, VWR), Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York.
Correspondence: Address correspondence and reprint requests to: Bhuvanesh Singh, MD, FACS, Head and Neck Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021; Fax: 212–717-3304; Email: singhb{at}mskcc.org
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.
Key Words: Squamous cell carcinoma • Angiogenesis • Lung cancer
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