Decreased expression of thymidine phosphorylase/platelet-derived endothelial cell growth factor in basal cell carcinomas.
Thymidine phosphorylase (TP)/platelet-derived endothelial cell growth factor is associated with tumor angiogenesis. We evaluated the TP mRNA and protein expression in basal cell carcinomas (BCC) and in various skin tumors including numerous BCC histological simulants. Immunohistochemistry was performed on 99 paraffin sections of formalin-fixed skin tumors using monoclonal antibodies (mAb) against TP. TP mRNA levels were measured by real time RT-PCR in whole BCCs (wBCC) and laser capture microdissected (LCM) BCC tumor cells. TP immunostaining was negative in all BCC variants and in most of the benign trichogeneic tumors studied. By contrast, TP was constantly immunodetected in actinic keratosis (AK), squamous cell carcinomas (SCC), syringomatous carcinomas (SC), basosquamous carcinomas (BSC) and melanomas. TP mRNA levels were low and statistically not different in wBCC and normal skin but were strongly downregulated in LCM-BCC as compared with LCM-normal epidermis. We concluded that (i) anti-TP mAb is an useful marker to differentiate BCC from AK, SCC, BSC and SC but not from trichoblastic tumors, (ii) the lack of TP protein expression in BCC tumoral cells is linked to transcriptional regulatory mechanisms, (iii) the low TP mRNA levels in whole BCC may be related to the low intra-tumoral microvessel density, the slow growth and the very low metastatic potential of these tumors.
Stoebner
Pierre E
PE
UMR CNRS 5247 (IBMM), Université Montpellier I, Montpellier, France. pierre.stoebner@chu-nimes.fr
Le Gallic
Lionel
L
Berthe
Marie L
ML
Boulle
Nathalie
N
Lallemant
Benjamin
B
Marque
Myriam
M
Gaspard
Catherine
C
Delfour
Christophe
C
Lavabre-Bertrand
Thierry
T
Martinez
Jean
J
Meunier
Laurent
L
D002280:Basal Cell Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002281:Carcinoma, Basosquamous / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D055623:Keratosis, Actinic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D013939:Thymidine Phosphorylase / Q000096:biosynthesis / Q000235:genetics*
D012333:RNA, Messenger; D013939:Thymidine Phosphorylase