Molecular diagnosis of basal cell carcinoma and other basaloid cell neoplasms of the skin by the quantification of genes involved in hedgehog signaling pathway

2003 Fiscal Year Final Research Report Summary

• Project/Area Number: 14570802
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Dermatology
• Research Institution: KANAZAWA UNIVERSITY
• Principal Investigator: HATTA Naohito KANAZAWA UNIVERSITY, School of Medicine, Associate professor, 医学部附属病院, 講師 (30272959)
• Co-Investigator(Kenkyū-buntansha): SHIRASAKI Fumiaki KANAZAWA UNIVERSITY, School of Medicine, Trainer, 医学系研究科, 助手 (10313644)
• Project Period (FY): 2002 – 2003
• Keywords: skin tumor / Gli / PTCH

Research Abstract

Distinguishing basal cell carcinoma (BCC) from other benign appendageal tumors is sometimes a difficult task for the pathologists. Since the activation of hedgehog signals is well documented in BCC, a molecular technique measuring transcripts of genes involved in this signaling pathway may aide the diagnosis.To assess whether a real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR) measuring Gli1, Gli2 and patched (PTCH) mRNA expression is of help in the classification of basaloid cell neoplasms of the skin.Sixty-eight cases of skin tumors including14BCCs, 12 squamous cell carcinomas(SCCs), 8 seborrheic keratoses, and 34 basaloid cell neoplasms of the skin with ambiguous histologic diagnosis.Measurement of Gli1, Gli2 and PTCH transcript levels by real-time quantitative RT-PCR using RNA extracted from formalin-fixed, paraffin-embedded tissues.Independent review of hematoxilin and eosin-stained pathology slides of 34 ambiguous cases by three expert dermatopathologists.The expression of Gli1, Gli2 and PTCH mRNA were significantly elevated in BCCs while being absent in SCCs and seborrheic keratoses.Among the three genes examined, Gli1 was the most sensitive and specific marker for discriminating BCC from other tumors.Pathological diagnosis by the three experts was concordant in 19 of 34 ambiguous cases.Tumors designated as BCC (7) and trichoepithelioma(5) showed high Gli1 transcript levels, whereas expression was undetectable in sebaceous epithelioma/carcinoma(2), eccrine poroma/porocarcinoma(5) and Bowen's disease(1).Although trichoepithelioma was not discriminated from BCC by the Gli1 transcript level alone, the mean PTCH transcript level and the mean PTCH/Gli2 ratio were both significantly lower in trichoepithelioma than in BCC.Quantification of Gli1, Gli2 and PTCH transcripts by RT-PCR is helpful in discriminating BCC from other appendageal tumors.