The role of novel oncogenes squamous cell carcinoma-related oncogene and phosphatidylinositol 3-kinase p110α in squamous cell carcinoma of the oral tongue Journal Article

Authors: Estilo, C. L.; O-Charoenrat, P.; Ngai, I.; Patel, S. G.; Reddy, P. G.; Su, D.; Shaha, A. R.; Kraus, D. H.; Boyle, J. O.; Wong, R. J.; Pfister, D. G.; Huryn, J. M.; Zlotolow, I. M.; Shah, J. P.; Singh, B.
Article Title: The role of novel oncogenes squamous cell carcinoma-related oncogene and phosphatidylinositol 3-kinase p110α in squamous cell carcinoma of the oral tongue
Abstract: Purpose: Amplification at chromosome 3q26.3 is a common and crucial event in head and neck squamous cell carcinoma (HNSCC), impacting significantly on tumor progression and clinical outcome. Two novel oncogenes, namely squamous cell carcinoma (SCC)-related oncogene (SCCRO) and PIK3CA (gene encoding phosphatidylinositol-3 kinase catalytic α-polypeptide), have been identified as targets of 3q26.3 amplification. This study aimed to delineate the role of SCCRO and PIK3CA in the pathogenesis of oral tongue SCC. Experimental Design: The association between gene copy number for SCCRO and PIK3CA measured by fluorescence in situ hybridization and level of mRNA expression quantitated by real-time reverse transcription-PCR was assessed in a panel of human HNSCC cell lines. In addition, gene expression in 49 consecutive primary SCCs of the oral tongue was determined and correlated with clinicopathological characteristics and outcome. Results: The mRNA level of SCCRO and PIK3CA was significantly correlated to the gene copy number in nine HNSCC cell lines. In addition, the expression level of SCCRO and PIK3CA was significantly greater in malignant tissues compared with those in histologically normal mucosae (2.17- and 2.46-fold, respectively; P < 0.001). Matched tumor normal control analysis revealed that 24.5 and 69.4% of patients expressed high levels of SCCRO and PIK3CA, respectively. Univariate analyses demonstrated that SCCRO overexpression correlated with nodal metastases (P = 0.05) and advanced stage (P = 0.02), whereas PIK3CA overexpression was associated with vascular invasion (P = 0.04). Only SCCRO overexpression was associated with disease-specific (P = 0.04) and overall survival (P = 0.02). Furthermore, SCCRO overexpression remained an independent predictor for cervical nodal metastasis on multivariate regression analysis (χ2 likelihood ratio = 4.38; P = 0.04). Conclusions: Although both SCCRO and PIK3CA may play a role in the pathogenesis of oral tongue SCC through amplification at 3q26, SCCRO appears to be a significant predictor of regional metastasis and may be a marker for tumor aggressiveness and clinical outcome.
Keywords: adult; cancer survival; controlled study; human tissue; aged; aged, 80 and over; middle aged; human cell; histopathology; pathogenesis; squamous cell carcinoma; carcinoma, squamous cell; advanced cancer; cancer growth; cancer staging; lymph node metastasis; lymphatic metastasis; gene targeting; in situ hybridization, fluorescence; gene overexpression; reverse transcription polymerase chain reaction; gene amplification; gene expression; genetic association; cell line, tumor; phosphatidylinositol 3 kinase; tumor marker; oncogenes; cancer invasion; oncogene; fluorescence in situ hybridization; messenger rna; 1-phosphatidylinositol 3-kinase; gene dosage; protein subunits; cervical lymph node; tongue neoplasms; tongue carcinoma; head and neck carcinoma; chromosome 3q; humans; human; male; female; priority journal; article
Journal Title: Clinical Cancer Research
Volume: 9
Issue: 6
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2003-06-01
Start Page: 2300
End Page: 2306
Language: English
PUBMED: 12796399
PROVIDER: scopus
Notes: Export Date: 12 September 2014 -- Source: Scopus
Citation Impact
MSK Authors
  1. Pabbathi G Reddy
    8 Reddy
  2. Joseph M Huryn
    84 Huryn
  3. Dennis Kraus
    268 Kraus
  4. Ashok R Shaha
    582 Shaha
  5. Jay O Boyle
    106 Boyle
  6. Bhuvanesh Singh
    219 Singh
  7. Snehal G Patel
    322 Patel
  8. Cherry Estilo
    69 Estilo
  9. David G Pfister
    301 Pfister
  10. Richard J Wong
    259 Wong
  11. Dao Su
    8 Su
  12. Jatin P Shah
    616 Shah
  13. Ivan Ngai
    17 Ngai