Stat3: A risk predictor in oral carcinogenesis.

doi:10.1016/j.oos.2009.06.593

P3.68. Cancer stem cells as mediators of treatment resistance insquamous cell carcinoma of the head and neckA. Okamoto a,*, K. Chikamatsu a, K. Sakakura b, K. Hatsushika b, G.Takahashi a, K. Masuyama a

a University of Yamanashi, Japanb University of Pittsburgh Cancer Institute, United States

Squamous cell carcinoma of the head and neck (SCCHN) containsa heterogenous population of cancer cells. Evidence has accumulatedindicating that only a minority of cancer cells with stem cell proper-ties, cancer stem cells (CSCs), is responsible for initiating, maintain-ing, and expanding the tumor growth. CD44 is currently used toidentify CSCs as one of the cell surface markers for SCCHN.

In this study, we investigated the identification, expansion, andcharacterization of CD44+ cancer stem-like cells from a SCCHN cellline. Under serum-free medium culture conditions, we enriched asubpopulation of CD44+ cells that possesses a marked capacity forforming tumor spheres, proliferation, migration, and invasionin vitro. Furthermore, the CD44+ cell population that had been puri-fied using immunomagnetic beads was significantly more resistantto various chemotherapeutic agents including carboplatin, doce-taxel, paclitaxel, 5-FU, and cisplatin than the CD44� cell population.Gene expression analysis demonstrated that CD44+ cells expressed ahigher level of ABCB1, ABCG2, CYP2C8, and TERT than CD44� cells.Moreover, the CD44+ cell population was also resistant to apoptosisinduced by other proapoptotic stimuli. Thus, various molecularmechanisms appear to be involved in the treatment resistance ofCD44+ cells.

Our findings suggest that the presence of such CSCs with thepotential to survive conventional treatment regimens has importantclinical implications for head and neck cancer treatment. Furtherstudy of CSCs in SCCHN may facilitate the development of noveltherapies against this devastating disease.

doi:10.1016/j.oos.2009.06.594

P3.69. Cytokeratins as prognostic markers in oral cancerD. Chaukar a,*, P. Pai a, M. Vaidya b, P. Chaturvedi a, V. Sawant b, A.Dcruz a

a Tata Memorial Hospital, Indiab Advanced Centre for Treatment, Research and Education in Cancer,India

Introduction: The search for prognostic factors in oral cancers isongoing. Intermediate filaments (IFs) have proved to be valuablemarkers because of their high order of cell and tissue specificity.We present a Prospective study to define the expression pattern ofcytokeratin 1, 5,8,18 and Vimentin in squamous cell carcinoma oforal cavity, cut margins, surrounding normal mucosa and correlatethe expression patterns with clinical parameters.

Methods: Study included 48 patients who underwent surgerywith neck dissection between 2003–2004. Immunohistochemistrywas done on formalin fixed, paraffin embedded sections by usingmonoclonal antibodies specific for CK 1, 5, 8, 18 and vimentin.

Results: Tumor showed aberrant expression of CK1 in 30%, CK8 in54%, CK18 in 44% and vimentin in 85%. CK5 non expression seen in

29%. In patients with tumor expressing 8, 18 and vimentin, 57% werepoorly, 36% moderately, and 7% well differentiated. 43% showed no-dal involvement when all 3 markers were positive and 36% of pa-tients developed recurrence. In cut margins, When 8, 18 were notexpressed with CK5 expression, 13% developed recurrence as com-pared to 33% when they were expressed. CK18 was expressed in35% of the cut margins specimen of which 53% developed recurrence(8 pts). CK 5 expression was seen in all patients with recurrence. Inpatients who developed recurrence within 6 months, cut marginsshowed CK 8 or 18 expressions with Vimentin in 88% (7/8) patients.

Conclusions: Cytokeratin 8, 18 and vimentin expression patternsexhibit definite relationship with oral cancers. CK18 expression incut margins is reliable marker to predict recurrence.

Vimentin, although a diagnostic tool, had limited value as a prog-nostic indicator. CK 5 aberrant expression was seen in all patientswith recurrence. The aberrant expression of keratin like CK 8 and18 seems to have a greater prognostic value than the non expressionof CK5.

doi:10.1016/j.oos.2009.06.595

P3.70. Transforming growth factor beta-1 (TGF beta-1) polymor-phisms are infrequent but exist in selected loci in oral submu-cous fibrosisR. Rajendran *, R.K. Harish, P. Vidhyadharan, S. Anil, M. Banerjee

College of Dentistry, King Saud University, Riyadh 11545, Saudi Arabia

Aim: Oral submucous fibrosis (OSF) is a potent precancerous con-dition of the oral mucosa, assuming epidemicproportions in the In-dian subcontinent. The nature of this disease remains enigmaticand the pathogenesis remains obscure. An attempt is made here toinvestigate the role of transforming growth factor beta-1 gene poly-morphism inthe pathogenesis of oral submucous fibrosis.

Materials and methods: The current study included 24 patientswithoral submucous fibrosis and 24 healthy controls. Seven poly-morphisms in TGFb 1 gene were selected for the study.They includethree polymorphisms [Arg25Pro, Leu10Pro, and Glu47Gly] in exon 1,two polymorphisms (G-800A and C-509T) in promoter region andtwo polymorphisms in 50UTR region (rs13306708 (C > T)and-rs9282871(G > A)). Blood samples were collected from the patientsas well as controls and DNA was isolated from it. Specificprimerswere used for amplifying the target regions and following itsequencing was performed. The polymorphisms were analysed bychecking the sequenced data using Bioedit� software.

Results: The significance of thepolymorphisms was analysedusing Hardy Weinberg equilibrium. A p value less than 0.05 is con-sidered to besignificant. There was no statistically significant differ-ence in the genotypic or allelic frequency distributionsbetweenpatient and control group in all the three polymorphisms of exon1, two polymorphisms of promoter regionand one polymorphism(rs9282871) in 50UTR region. But a p value of 0.03 was obtainedfor the C to T polymorphism (rs13306708) in 50UTR region and henceit can be considered to be significant. The role of thispolymorphismin the pathogenesis of oral submucous fibrosis is discussed.

Conclusion: The polymorphism in 50UTR C–T in TGF b1 gene hasa significant association with OSF, being a prime determinant in thepro-angiogenicpathway which has got direct bearing with the path-ophysiology of the disease. The proximity of this polymorphism tothe transcription binding site and the associated risk factor isdiscussed.

doi:10.1016/j.oos.2009.06.596

224 Poster session III et al. / Oral Oncology Supplement 3 (2009) 201–236

Com

mit

tee

List

ings

Wel

com

eIA

OO

Prog

ram

Key

not

eB

ios.

Key

not

eA

bs.

Pan

.Dis

c.&

Sym

p.A

bs.

Ora

lsLi

stPo

ster

List

Ora

lA

bstr

acts

Post

erA

bstr

acts