Losses of FHIT and p16 in oral carcinogenesis – a FISH based study Johannes Bier

background – „leukoplakia“1/2 oral leukoplakia main epithelial lesion of the mucosa of the mouth (prevalence: 2.3%) heterogeneous group with varying risk premalignant epithelial precursor lesion of OSCC (3-8% transform into cancer) whitish patches several grades: hyperplasia, low/high grade dysplasia, CIS, invasive cancer mainly due to carcinogens, i.e. nicotine, alcohol, but also idiopathic

background – „leukoplakia“ 2/2 no standardized regime for treatment follow-up with biopsy and histopathology currently gold standard molecular biological techniques to be future proposals ? no specific markers to predict malignant transformation yet LOH and polyploidy ?

so what?

there are hints... molecular progression model for oral carcinogenesis: accumulation of genetic changes (Califano et al.,1996) (adopted from Fearon & Vogelstein 1990: colon cancer) studies on LOH proposed 3p and 9p to be important for progression (Rosin et al., 2000; Mao et al.,1996) greater probability of progression into OSCC

3p and 9p... 3p14 alias FHIT (fragile histidine triade), 9p21 alias p16 both tumor suppressor genes considered to indicate transition from hyperplasia to dysplasia

FISH what?! leukoplakia with hyperplasia – probes for FHIT centromere gene

FISH what?! invasive carcinoma – probes for FHIT centromer gene

results - deletion FHIT / p16

results - polysomy FHIT / p16

discussion already >90% of hyperplasia deletion for FHIT  Califano et al. = 20% our threshold: 25% / 13%  LOH studies 50% FHIT earlier event than p16; results underline role of FHIT regarding cell cycle regulation possibility to distinguish deletion – amplification hyperplasia does not show polysomy 3p or 9p polysomy 3 indicator of increasing oral carcinogenesis