plgf overexpression in head and neck squamous cell carcinoma

1
and neck cancer. Unfortunately, even with early detection of recurrent disease, the mortality rate remains high. PET-CT for Head and Neck SCC Unknown Primary Joseph Dort, MSc, MD (presenter) OBJECTIVE: 1) Understand the work-up options for evalua- tion of head and neck unknown primary. 2) Understand the role of PET-CT in the evaluation of head and neck unknown primary. METHOD: 20 subjects with PUK were enrolled in a prospec- tive clinical trial. A standard protocol was used in both clinic and operating room (OR). Study surgeons were blinded to the PET-CT result upon completion of the standard workup. RESULTS: PET-CT increased the detection of a primary site from 25% to 55% (5 vs 11 subjects). This difference was statistically and clinically significant (p0.03, McNemars test). There was one false negative PET-CT scan. CONCLUSION: PUK should be diagnosed after a complete head and neck examination, flexible endoscopy and CT or MRI. PET-CT performed prior to panendoscopy will increase the diagnostic yield in the PUK population leading to more targeted, and less morbid, treatment. Plasma EBV DNA Levels for Surveillance in NPC Patients Thomas Loh, FRCS (presenter) OBJECTIVE: To determine the trend of EBV VCA IgA, EBV Ea IgA, and Plasma EBV DNA levels in nasopharyngeal (NPC) patients post treatment, and to compare the trend of the levels between patients who remain disease-free and those who develop recurrence, with an aim to identify predictive patterns of recurrence. METHOD: From February 2004 to December 2006, 60 newly diagnosed NPC patients were included prospectively. EBV VCA IgA, EBV Ea IgA, and plasma EBV DNA levels were taken at diagnosis, repeated annually or at time of recurrence. Patient demographics, stage and date of recurrence were col- lected. Analysis of the trends of plasma EBV DNA in patients who recurred was compared with those without disease. RESULTS: The follow-up period ranged from 36 to 70 months. There were 16 patients with recurrence (Group 1), and 44 were disease-free (Group 2). The median plasma EBV DNA levels for Groups 1 and 2 at the time of diagnosis was 1092.99 copies/ml and 544.4 copies/ml, respectively. At 1 year post-radiation, 37.5% in Group 1 vs 9.1% in Group 2 showed an upward trend of the EBV DNA levels. No significant trends were detected in VCA and Ea levels. No correlation was seen between EBV VCA, Ea and plasma EBV DNA levels. CONCLUSION: Rising plasma EBV DNA levels at 1 year post-radiation may be a better predictor of disease recurrence than absolute levels at the time of diagnosis. PlGF Overexpression in Head and Neck Squamous Cell Carcinoma James Byrd, MD (presenter); Brian Hoel, PhD; Semyon Rubinchik, PhD; M Boyd Gillespie, MSc, MD; Natalie Sutkowski, PhD OBJECTIVE: Placental Growth Factor (PlGF) is a member of the Vascular Endothelial Growth Factor (VEGF) family that signals through the VEGF-R1 receptor. Unlike VEGF, PlGF has a limited role in expression in normal tissue, but has been shown by microarray analysis and immunohistochemistry to be upregulated in tumors, including head and neck squamous cell carcinomas (HNSCC). The purpose of this study is to determine the expression of Placenta Growth Factor (PlGF) in head and neck squamous cell carcinoma relative to normal tissue. METHOD: Seventeen head and neck squamous cell carci- noma (HNSCC) frozen tumor specimens and five benign uvula specimens were obtained through a tertiary care hospital’s tissue biorepository. Total RNA was extracted from each sam- ple and reverse transcribed to cDNA. Expression of PlGF and endogenous standard GAPDH were measured by quantitative polymerase chain reaction. A human choriocarcinoma cell line (JAR) was used as a positive control. The results were nor- malized against one of the uvula samples, and were recorded for each sample as the logarithm of the relative quantitation (Log10(RQ)). The average values for the uvula and tumor samples were compared using a two-tailed t-test. RESULTS: Seventeen HNSCC tumor samples and five nor- mal oropharyngeal samples were analyzed. Tumor subsites included oral cavity (n12, 70%), oropharynx (n4, 24%), and supraglottis (n1, 6%). PlGF expression was significantly higher (p0.001) in the tumor specimens compared with the benign uvula specimens. The average Log10(RQ) value for tumor samples was 0.353 (/- 0.458), while the average value for the benign uvulae was -0.0745 (/- 0.108). CONCLUSION: PlGF was expressed at a significantly higher level in squamous cell carcinoma compared to normal orophar- ynx. A larger sample size is needed for delineation of associ- ated features. Testing of additional tumor samples is currently underway. Polymorphisms of Aurora-A Gene in Oral Cancer Chang-Han Chen, PhD (presenter); Chih-Yen Chien, MD OBJECTIVE: Aurora-A, a serine/threonine kinase, localized at centrosome, assists chromosomal separation and mitotic spindle stability during mitosis. We hypothesize that Aurora-A polymorphisms might modulate the risk of oral cancer. METHOD: We used a hospital-based case-control study to assess the association between Aurora-A polymorphisms and risk of oral cancer. Cases and controls were matched on age, race, and smoking status. The single nucleotide polymor- P196 Otolaryngology-Head and Neck Surgery, Vol 143, No 2S2, August 2010

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and neck cancer. Unfortunately, even with early detection ofrecurrent disease, the mortality rate remains high.

PET-CT for Head and Neck SCC Unknown Primary

Joseph Dort, MSc, MD (presenter)

OBJECTIVE: 1) Understand the work-up options for evalua-tion of head and neck unknown primary. 2) Understand therole of PET-CT in the evaluation of head and neck unknownprimary.METHOD: 20 subjects with PUK were enrolled in a prospec-tive clinical trial. A standard protocol was used in both clinicand operating room (OR). Study surgeons were blinded to thePET-CT result upon completion of the standard workup.RESULTS: PET-CT increased the detection of a primary sitefrom 25% to 55% (5 vs 11 subjects). This difference wasstatistically and clinically significant (p�0.03, McNemarstest). There was one false negative PET-CT scan.CONCLUSION: PUK should be diagnosed after a completehead and neck examination, flexible endoscopy and CT orMRI. PET-CT performed prior to panendoscopy will increasethe diagnostic yield in the PUK population leading to moretargeted, and less morbid, treatment.

Plasma EBV DNA Levels for Surveillance in NPC

Patients

Thomas Loh, FRCS (presenter)

OBJECTIVE: To determine the trend of EBV VCA IgA, EBVEa IgA, and Plasma EBV DNA levels in nasopharyngeal(NPC) patients post treatment, and to compare the trend of thelevels between patients who remain disease-free and those whodevelop recurrence, with an aim to identify predictive patternsof recurrence.METHOD: From February 2004 to December 2006, 60 newlydiagnosed NPC patients were included prospectively. EBVVCA IgA, EBV Ea IgA, and plasma EBV DNA levels weretaken at diagnosis, repeated annually or at time of recurrence.Patient demographics, stage and date of recurrence were col-lected. Analysis of the trends of plasma EBV DNA in patientswho recurred was compared with those without disease.RESULTS: The follow-up period ranged from 36 to 70months. There were 16 patients with recurrence (Group 1), and44 were disease-free (Group 2). The median plasma EBVDNA levels for Groups 1 and 2 at the time of diagnosis was1092.99 copies/ml and 544.4 copies/ml, respectively. At 1 yearpost-radiation, 37.5% in Group 1 vs 9.1% in Group 2 showedan upward trend of the EBV DNA levels. No significant trendswere detected in VCA and Ea levels. No correlation was seenbetween EBV VCA, Ea and plasma EBV DNA levels.CONCLUSION: Rising plasma EBV DNA levels at 1 yearpost-radiation may be a better predictor of disease recurrencethan absolute levels at the time of diagnosis.

PlGF Overexpression in Head and Neck Squamous

Cell Carcinoma

James Byrd, MD (presenter); Brian Hoel, PhD;Semyon Rubinchik, PhD; M Boyd Gillespie, MSc,MD; Natalie Sutkowski, PhD

OBJECTIVE: Placental Growth Factor (PlGF) is a member ofthe Vascular Endothelial Growth Factor (VEGF) family thatsignals through the VEGF-R1 receptor. Unlike VEGF, PlGFhas a limited role in expression in normal tissue, but has beenshown by microarray analysis and immunohistochemistry tobe upregulated in tumors, including head and neck squamouscell carcinomas (HNSCC). The purpose of this study is todetermine the expression of Placenta Growth Factor (PlGF) inhead and neck squamous cell carcinoma relative to normaltissue.METHOD: Seventeen head and neck squamous cell carci-noma (HNSCC) frozen tumor specimens and five benign uvulaspecimens were obtained through a tertiary care hospital’stissue biorepository. Total RNA was extracted from each sam-ple and reverse transcribed to cDNA. Expression of PlGF andendogenous standard GAPDH were measured by quantitativepolymerase chain reaction. A human choriocarcinoma cell line(JAR) was used as a positive control. The results were nor-malized against one of the uvula samples, and were recordedfor each sample as the logarithm of the relative quantitation(Log10(RQ)). The average values for the uvula and tumorsamples were compared using a two-tailed t-test.RESULTS: Seventeen HNSCC tumor samples and five nor-mal oropharyngeal samples were analyzed. Tumor subsitesincluded oral cavity (n�12, 70%), oropharynx (n�4, 24%),and supraglottis (n�1, 6%). PlGF expression was significantlyhigher (p�0.001) in the tumor specimens compared with thebenign uvula specimens. The average Log10(RQ) value fortumor samples was 0.353 (�/- 0.458), while the average valuefor the benign uvulae was -0.0745 (�/- 0.108).CONCLUSION: PlGF was expressed at a significantly higherlevel in squamous cell carcinoma compared to normal orophar-ynx. A larger sample size is needed for delineation of associ-ated features. Testing of additional tumor samples is currentlyunderway.

Polymorphisms of Aurora-A Gene in Oral Cancer

Chang-Han Chen, PhD (presenter); Chih-Yen Chien,MD

OBJECTIVE: Aurora-A, a serine/threonine kinase, localizedat centrosome, assists chromosomal separation and mitoticspindle stability during mitosis. We hypothesize that Aurora-Apolymorphisms might modulate the risk of oral cancer.METHOD: We used a hospital-based case-control study toassess the association between Aurora-A polymorphisms andrisk of oral cancer. Cases and controls were matched on age,race, and smoking status. The single nucleotide polymor-

P196 Otolaryngology-Head and Neck Surgery, Vol 143, No 2S2, August 2010