The role of novel oncogenes squamous cell carcinoma-related oncogene and phosphatidylinositol 3-kinase p110alpha in squamous cell carcinoma of the oral tongue.
OBJECTIVE
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 alpha-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.


METHODS
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 (chi(2) 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.
Estilo
Cherry L
CL
Dental Service, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
O-Charoenrat
Pornchai
P
Ngai
Ivan
I
Patel
Snehal G
SG
Reddy
Pabbathi G
PG
Dao
Su
S
Shaha
Ashok R
AR
Kraus
Dennis H
DH
Boyle
Jay O
JO
Wong
Richard J
RJ
Pfister
David G
DG
Huryn
Joseph M
JM
Zlotolow
Ian M
IM
Shah
Jatin P
JP
Singh
Bhuvanesh
B
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D018628:Gene Dosage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009857:Oncogenes / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D021122:Protein Subunits; D014062:Tongue Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology
D021122:Protein Subunits; D019869:Phosphatidylinositol 3-Kinases