SLIDE 1 The Role of the Surgical Pathologist in The Role of the Surgical Pathologist in the Molecular Diagnosis of Head and Neck Cancer
8th
th P i
M H i l P i M H i l
Neck Cancer
8th
th Princess Margaret Hospital
Princess Margaret Hospital Conference Conference
B d P O d ñ M D
October 16 October 16-
18, 2008
Bayardo Perez-Ordoñez, M.D. Department of Pathology University Health Network Department of Laboratory Medicine and Pathobiology University of Toronto Toronto, Ontario, Canada
SLIDE 2
Traditional Role of the Surgical Pathologist in Head and Neck Squamous Cell Carcinoma Diagnosis and Neck Squamous Cell Carcinoma g Evaluation of Prognostic Factors and Pathologic Evaluation of Prognostic Factors and Pathologic Staging Completeness of resection Evaluation of presence/absence of metastases
SLIDE 3
Molecular Alterations in Head and Neck Squamous cell Carcinoma
Normal mucosa Hyperplasia Dysplasia Carcinoma in-situ Squamous cell carcinoma
Carcinoma
9p21 deletion 16/ 14 3p deletions 17 13 ( 53 11q13 18q deletion p16/p14 inactivation Trisomy 7 EGFR 17p13 (p53 mutations) Tetraploidy 13q21 8p deletion Aneuploidy 10q23 3q26 PTEN i i i EGFR Telomerase activation Cyclin D1 amplification inactivation
SLIDE 4
Molecular Alterations Associated with metastasis in Squamous Cell Carcinoma Squamous Cell Carcinoma E-cadherin CXCR4-SDF1 VGEF(R)s, PDGF(R)s FGR(R)s, TGFα/β G ( )s, G α/β Interleukin-8 MMPs LOH: 6p 4q27 10q23 LOH: 6p, 4q27, 10q23
SLIDE 5
Squamous Cell Carcinoma, p53 and EGFR p53 EGFR
SLIDE 6
Nonkeratinizing Squamous Cell Carcinoma p16
SLIDE 7 HPV PCR
10(-3) 10(-4) arker
Consensus primers HPV 16 primers
Reagent Negative
Patient
HPV (+ ) HPV (+ ) 50 bp Ma r (-4) (-5) Reagent 50 bp Marker Negative
Patient
CaSki (+ ) 10 CaSki (+ ) 10 00 b HPV MY09/11 452 bp 250 bp 400 bp Internal Control 423 bp 100 bp HPV 16F/R 96 bp
SLIDE 8
HPV in-situ hybridization
SLIDE 9 HPV-Linear Array Results
β globin Low β-globin High β -globin Low
Positive Control Low Positive Positive Negative I nconclusive Low Positive Positive Negative Reagent Contro l
SLIDE 10 WHO Classification of Nasopharyngeal Carcinoma
- Keratinizing squamous cell carcinoma
- Nonkeratinizing carcinoma
Differentiated type Undifferentiated type
- Basaloid squamous cell carcinoma
SLIDE 11
Nonkeratinizing Carcinoma, Undifferentiated-type
SLIDE 12 EBV-DNA serum levels and monitoring of NPC
Patient 3
EBV copy number: Plasma 100000
chemotherapy
g
89230.7 70000 80000 90000 100000 es/mL)
Ab l
40000 50000 60000 DNA (copie
Abnormal PET/MRI XRT Normal PET/CNED
182 9 0 52 10000 20000 30000 EBV D
65/F, T4N2, CRT, PET: normal, MRI: residual abnormality, CNED
182.9 0.52 26-Nov-01 21-Dec-01 7-Jan-02 follow-up samples
SLIDE 13
Mucoepidermoid Carcinoma
Grade I Grade II Grade III
SLIDE 14
CRTC1/ MAML2 fusion transcript and t(11;19) in Mucoepidermoid Carcinoma p
http://atlasgeneticsoncology.org/Genes/Images/CRTC1
SLIDE 15
The prevalence of t(11;19) in mucoepidermoid carcinoma has ranged from 38-88% 38% carcinoma has ranged from 38-88% . 38% 55% 88%
SLIDE 16
CRTC1-MAML2 positive tumors appear to have a better prognosis than CRTC1-MAML2 negative tumors.
Behboudi et al. Genes Chromosomes Cancer 2006;45:470-481 Okabe, M. et al. Clin Cancer Res 2006;12:3902-3907
SLIDE 17
Salivary Duct Carcinoma
Her2Neu Her2Neu FISH
