Expression of p53 family members and CD44 in oral squamous cell carcinoma (OSCC) in relation to tumorigenesis.
Oral squamous cell carcinomas (OSCCs) are described as the result of a multistep tumorigenesis process. In order to develop useful diagnosis of pre-malignant lesions, expression of p53 family members and the cancer stem cell (CSCs) marker, CD44v6, were studied in histologically normal oral epithelium, precancerous lesions and succeeding invasive OSCCs. p53 was expressed focally in normal epithelium adjacent to tumors, while expression was high in intra-epithelial neoplasia and moderate in OSCC. p63 nuclear staining was important in basal and suprabasal layers of histologically normal oral mucosa and in immature compartments of premalignant lesions and cancer. In epithelium without neoplasia, intense p73 staining was observed in the basal layer, while focal expression was present in suprabasal layers. Most immature dysplastic areas showed either high or moderate staining, whereas those in OSCCs expressed low and moderate p73 level expression. CD44v6 was only expressed in poorly differentiated areas of epithelium, altered or not. p53, p63 and p73 positive stainings were statistically related in intra-epithelial neoplasia to tumours. Analysis of TP53 mutations in 17% of tumours principally revealed G>A and A>G transitions. No relation was observed between this mutational profile and different immunostainings. In conclusion, our results support that immunostaining of p53 family members might be helpful in diagnosis and monitoring of high-risk pre-malignant lesions of oral epithelium. The combination of staining patterns of p63, p73alpha and CD44v6 enabled us to isolate phenotypic undifferentiated or transient amplifying areas, reflecting the immaturity of the tumour cell lineage. While CD44v6 expression is an interesting marker of such epithelial cells, it is not specific enough to be useful alone and other phenotypic markers are needed.
Bidaud
Pauline
P
GRECAN-IFR146 ICORE, François Baclesse Center and University of Caen, Caen, France.
Chasle
Jacques
J
Sichel
François
F
Rousseau
Stéphane
S
Petit
Pascal
P
Pottier
Didier
D
Picquenot
Jean-Michel
JM
Louis
Marie-Yolande
MY
Lechevrel
Mathilde
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics* / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
C112697:CD44v6 antigen; C081876:CKAP4 protein, human; D004268:DNA-Binding Proteins; D018960:Hyaluronan Receptors; D008565:Membrane Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins