title: Selective in situ protein expression profiles correlate with distinct phenotypes of basal cell carcinoma and squamous cell carcinoma of the skin.
abstract: Non-melanoma skin cancer is the most common malignancy that shows increasing incidence due to our cumulative exposure to ultraviolet irradiation. Its major subtypes, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) differ in pathobiology, phenotype and clinical behavior, which must be reflected at the molecular level. In this study, protein expression profiles of BCC and SCC were tested in tissue microarrays and correlated with that of actinic keratosis, Bowen's disease, seborrheic keratosis and normal epidermis by detecting 22 proteins involved in cell interactions, growth, cell cycle regulation or apoptosis. The significantly more reduced collagen XVII, CD44v6, pan-Desmoglein levels and more evident E-Cadherin delocalization in BCC compared to SCC correlated with the de novo dermal invasion of BCC against the progressive invasion from in situ lesions in SCC development. EGFR was also expressed at a significantly higher level in SCC than in BCC. The upregulated cell communication protein connexin43 in BCC could contribute to the protection of BCC from metastatic invasion. Elevated cell replication in BCC was underlined by the increased topoisomerase IIα and reduced p21(waf1) and p27(kip1) positive cells fractions compared to SCC. Compared to differentiated keratinocytes, caspase-8 and -9 were equally upregulated in skin carcinoma subtypes for either mediating apoptosis induction or immune escape of tumor cells. Hierarchical cluster analysis grouped SCC and actinic keratosis cases exclusively together in support of their common origin and malignant phenotype. BCC cases were also clustered fully together. Differentially expressed proteins reflect the distinct pathobiology of skin carcinoma subtypes and can serve as surrogate markers in doubtful cases.
authors: Laboratory of Tumor Pathology and Molecular Diagnostics, Bay Zoltan Foundation for Applied Research, Szeged, Hungary.
authors: E
authors: E
authors: Stelkovics
authors: G
authors: G
authors: Kiszner
authors: N
authors: N
authors: Meggyeshazi
authors: I
authors: I
authors: Korom
authors: E
authors: E
authors: Varga
authors: I
authors: I
authors: Nemeth
authors: J
authors: J
authors: Molnar
authors: I
authors: I
authors: Marczinovits
authors: T
authors: T
authors: Krenacs
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D001706:Biopsy; D002280:Basal Cell Carcinoma / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D016000:Cluster Analysis; D003094:Collagen / Q000378:metabolism; D018031:Connexin 43 / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D012867:Skin / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism*
chemical_list: D018031:Connexin 43; D003094:Collagen; D066246:ErbB Receptors; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9