genomic profiling of head and neck cancer by cdna microarray analysis

1
Oral Abstract Session 4 PATHOLOGY AND MEDICINE/ORTHOGNATHIC SURGERY/TMJ/ MAXILLOFACIAL RECONSTRUCTION Friday, September 12, 2003, 1:00 pm–5:00 pm Extended Mid-Facial Translocation Approach for Nasopharyngecotmy M. Abraham Kuriakose, DDS, MD, Suite 7U, Skirball Building, NYU Medical Center, 530 First Avenue, New York, NY 10016 (Karlis V; Glickman R) Introduction: Nasopharyngectomy is emerging as an effective salvage treatment for locally recurrent nasopha- ryngeal cancer (NPC). The recurrent NPC has a predi- lection to extend posterolaterally into the paranasopha- ryngeal and infratemporal fossa region. Surgical proce- dures which provide exposure of these regions are required for safe and oncologically sound resection of this tumor. In this report we describe the effectiveness of extended facial translocation approach for salvage nasopharyngectomy. Patients and Methods: Four patients with recurrent NPC following radiotherapy underwent extended facial translocation approach for nasopharyngectomy of stage rT2b to rT4 tumors. The inclusion criteria for this pro- cedure consisted of locally recurrent NPC with no evi- dence of distant metastasis and absence of carotid or dural invasion. The technique consists of translocation of maxilla, zygomatic bone, and nose along with their soft tissue envelope as a composite unit. The surgical defect was reconstructed using temporalis muscle to protect the carotid artery at the skull base. The patients received further radiation by brachytherapy (1,500 to 2,500 cGy). Results: All 4 patients had tumor resection with unin- volved margins. The postoperative complications con- sisted of a case of palatal fistula and enophthalmos. The patients were followed up for a period ranging from 24 to 48 months (mean 28 months). Local disease control was achieved in all but one patient. Three of the 4 patients remain free of disease. One patient is alive with local recurrance. Conclusions: The extended mid-facial translocation approach provides wide exposure of entire nasopharynx and the ipsilateral infratemporal fossa, enabling onco- logically sound resection of recurrent nasopharyngeal cancer with acceptable morbidity. References Ammirati M, Bernando A: Analytical evaluation of complex anterior approaches to the cranial base: An anatomic study. Neurosurgery 4:1398, 1998 Fisch U, Pillsbury HC: Infratemporal fossa approach to lesions of the temporal bone and base of skull. Arch Otolaryngol 105:99, 1979 Genomic Profiling of Head and Neck Cancer by cDNA Microarray Analysis David Hirsch, DDS, MD, NYU College of Dentistry, Department of OMS, 345 E 24th St, New York, NY 10010 (Kuriakose MA; Chen FA; Karlis V; Glickman R) Objectives: An overwhelming body of evidence sug- gests that the phenotypic diversity of head and neck squamous cell carcinomas (HNSCC) is preceded or ac- companied by corresponding genotypic changes. The objective of this study was to identify the altered gene expression of HNSCC. Methods: Isolated RNA from tumor and corresponding patient’s normal tissues was processed for hybridization to Affymetrix U95A GeneChip, which is a high density Cartesian-coordinate array containing ordered oligo-nu- cleotides of over 12,000 defined genes and expression sequence tags (ESTs). A total of 15 pairs of samples (30 chips) were investigated. The gene expression data was analyzed by GeneSpring, Excel, and Access software to identify significant differentially expressed genes. Valid- ity of these genes was carried out by RT-PCR and West- ern blot analysis. Results: A panel of genes with highest potential to be differentially expressed between tumor and normal tis- sue was identified with the following approaches: Best class predictor (GeneSpring), paired t test (Excel), and Comparison analysis (Access). In combination, 31 probes (27 gene/EST) were selected. These represent known oncogenes, tumor suppressor genes as well as novel genes. Conclusions: The genetic database created provides important insight into modeling gene expression changes implicated in HNSCC and suggests the future potential of identifying novel molecular markers for tumor detection and characterization of phenotypic diversity. References Villaret DB, Wang T, Dillon D, et al: Identification of genes overex- pressed in head and neck squamous cell carcinoma using a combina- tion of complementary DNA subtraction and microarrary analysis. Laryngoscope 110:374, 2000 Leethanakul C, Patel V, Gillespie J, et al: Distinct pattern of expres- sion of differentiation and growth-related genes in squamous cell carcinomas of the head and neck revealed by the use of laser capture microdissection and cDNA arrays. Oncogene 19:3220, 2000 Funding Source: George Hall Endowment Fund. AAOMS 2003 59

Upload: david-hirsch

Post on 16-Sep-2016

212 views

Category:

Documents


0 download

TRANSCRIPT

Oral Abstract Session 4

PATHOLOGY AND MEDICINE/ORTHOGNATHIC SURGERY/TMJ/MAXILLOFACIAL RECONSTRUCTIONFriday, September 12, 2003, 1:00 pm–5:00 pm

Extended Mid-Facial TranslocationApproach for NasopharyngecotmyM. Abraham Kuriakose, DDS, MD, Suite 7U, SkirballBuilding, NYU Medical Center, 530 First Avenue,New York, NY 10016 (Karlis V; Glickman R)

Introduction: Nasopharyngectomy is emerging as aneffective salvage treatment for locally recurrent nasopha-ryngeal cancer (NPC). The recurrent NPC has a predi-lection to extend posterolaterally into the paranasopha-ryngeal and infratemporal fossa region. Surgical proce-dures which provide exposure of these regions arerequired for safe and oncologically sound resection ofthis tumor. In this report we describe the effectivenessof extended facial translocation approach for salvagenasopharyngectomy.

Patients and Methods: Four patients with recurrentNPC following radiotherapy underwent extended facialtranslocation approach for nasopharyngectomy of stagerT2b to rT4 tumors. The inclusion criteria for this pro-cedure consisted of locally recurrent NPC with no evi-dence of distant metastasis and absence of carotid ordural invasion. The technique consists of translocationof maxilla, zygomatic bone, and nose along with theirsoft tissue envelope as a composite unit. The surgicaldefect was reconstructed using temporalis muscle toprotect the carotid artery at the skull base. The patientsreceived further radiation by brachytherapy (1,500 to2,500 cGy).

Results: All 4 patients had tumor resection with unin-volved margins. The postoperative complications con-sisted of a case of palatal fistula and enophthalmos. Thepatients were followed up for a period ranging from 24to 48 months (mean 28 months). Local disease controlwas achieved in all but one patient. Three of the 4patients remain free of disease. One patient is alive withlocal recurrance.

Conclusions: The extended mid-facial translocationapproach provides wide exposure of entire nasopharynxand the ipsilateral infratemporal fossa, enabling onco-logically sound resection of recurrent nasopharyngealcancer with acceptable morbidity.

References

Ammirati M, Bernando A: Analytical evaluation of complex anteriorapproaches to the cranial base: An anatomic study. Neurosurgery4:1398, 1998

Fisch U, Pillsbury HC: Infratemporal fossa approach to lesions of thetemporal bone and base of skull. Arch Otolaryngol 105:99, 1979

Genomic Profiling of Head and NeckCancer by cDNA Microarray AnalysisDavid Hirsch, DDS, MD, NYU College of Dentistry,Department of OMS, 345 E 24th St, New York, NY10010 (Kuriakose MA; Chen FA; Karlis V; Glickman R)

Objectives: An overwhelming body of evidence sug-gests that the phenotypic diversity of head and necksquamous cell carcinomas (HNSCC) is preceded or ac-companied by corresponding genotypic changes. Theobjective of this study was to identify the altered geneexpression of HNSCC.

Methods: Isolated RNA from tumor and correspondingpatient’s normal tissues was processed for hybridizationto Affymetrix U95A GeneChip, which is a high densityCartesian-coordinate array containing ordered oligo-nu-cleotides of over 12,000 defined genes and expressionsequence tags (ESTs). A total of 15 pairs of samples (30chips) were investigated. The gene expression data wasanalyzed by GeneSpring, Excel, and Access software toidentify significant differentially expressed genes. Valid-ity of these genes was carried out by RT-PCR and West-ern blot analysis.

Results: A panel of genes with highest potential to bedifferentially expressed between tumor and normal tis-sue was identified with the following approaches: Bestclass predictor (GeneSpring), paired t test (Excel), andComparison analysis (Access). In combination, 31probes (27 gene/EST) were selected. These representknown oncogenes, tumor suppressor genes as well asnovel genes.

Conclusions: The genetic database created providesimportant insight into modeling gene expression changesimplicated in HNSCC and suggests the future potential ofidentifying novel molecular markers for tumor detectionand characterization of phenotypic diversity.

References

Villaret DB, Wang T, Dillon D, et al: Identification of genes overex-pressed in head and neck squamous cell carcinoma using a combina-tion of complementary DNA subtraction and microarrary analysis.Laryngoscope 110:374, 2000

Leethanakul C, Patel V, Gillespie J, et al: Distinct pattern of expres-sion of differentiation and growth-related genes in squamous cellcarcinomas of the head and neck revealed by the use of laser capturemicrodissection and cDNA arrays. Oncogene 19:3220, 2000

Funding Source: George Hall Endowment Fund.

AAOMS • 2003 59