Squamous cell carcinoma related oncogene regulates angiogenesis through vascular endothelial growth factor-A Journal Article

Authors: Talbot, S. G.; O-Charoenrat, P.; Sarkaria, I. S.; Ghossein, R.; Reddy, P.; Ngai, I.; Cordeiro, C. N.; Wong, R. J.; Kris, M. G.; Rusch, V. W.; Singh, B.
Article Title: Squamous cell carcinoma related oncogene regulates angiogenesis through vascular endothelial growth factor-A
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. © 2004 The Society of Surgical Oncology, Inc.
Keywords: immunohistochemistry; signal transduction; survival; adult; cancer survival; clinical article; controlled study; aged; survival analysis; vascular endothelial growth factor a; cancer surgery; survival rate; genetics; squamous cell carcinoma; carcinoma, squamous cell; pathophysiology; phenotype; cd34 antigen; reverse transcription polymerase chain reaction; cohort studies; gene amplification; gene expression; lung non small cell cancer; carcinoma, non-small-cell lung; lung neoplasms; cohort analysis; lung cancer; angiogenesis; neovascularization, pathologic; oncogenes; lung tumor; rna; gene expression regulation; oncogene; gene expression regulation, neoplastic; correlation analysis; statistical significance; messenger rna; reverse transcriptase polymerase chain reaction; vasculotropin a; microvasculature; neovascularization (pathology); rna extraction; humans; prognosis; human; article
Journal Title: Annals of Surgical Oncology
Volume: 11
Issue: 5
ISSN: 1068-9265
Publisher: Springer  
Date Published: 2004-05-01
Start Page: 530
End Page: 534
Language: English
DOI: 10.1245/aso.2004.03.014
PROVIDER: scopus
PUBMED: 15123463
Notes: Ann. Surg. Oncol. -- Cited By (since 1996):13 -- Export Date: 16 June 2014 -- CODEN: ASONF -- Source: Scopus
Citation Impact
MSK Authors
  1. Pabbathi G Reddy
    8 Reddy
  2. Simon G Talbot
    26 Talbot
  3. Valerie W Rusch
    735 Rusch
  4. Ronald A Ghossein
    343 Ghossein
  5. Bhuvanesh Singh
    217 Singh
  6. Richard J Wong
    254 Wong
  7. Mark Kris
    716 Kris
  8. Ivan Ngai
    17 Ngai