p63 in laryngeal squamous cell carcinoma: evidence for a role of TA-p63 down-regulation in tumorigenesis and lack of prognostic implications of p63 immunoreactivity.
p63 is a p53-related gene that encodes for multiple mRNA transcripts with (TA-p63) or without (DeltaN-p63) transactivating properties on p53-responsive genes. We evaluated for the first time the prevalence and clinical implications of p63 immunoreactivity (IR) and mRNA expression in laryngeal squamous cell carcinomas (LSCCs). Moreover, we also assessed the relationships between p63 expression and p53 gene status. p63 IR was detectable in the basal cell layers of non-neoplastic epithelium and in the whole thickness of dysplastic epithelium. All the 150 LSCCs analyzed were immunoreactive for p63, with 28 (18.7%) cases showing p63 IR in </=50% of neoplastic cells. DeltaN-p63 mRNA transcripts were detected in all the 23 tumors analyzed, whereas TA-p63 mRNA transcripts were absent in 5 (21.7%) cases. p53 gene mutations were found in 24 (29.2%) of the 82 cases analyzed and p53 IR was found in 58 (53.7%) of the 108 cases analyzed; neither was associated with p63 IR. No significant association was found between p63 IR and patients' survival. Interestingly, down-regulation of TA-p63 mRNA levels was more prevalent in patients with T3-T4 tumors and advanced clinical stage. Although the risk of death for cancer was higher in these patients (40% versus 16.6%), this difference did not reach statistical significance. Our results suggest that abnormal expression of p63 may be involved in the early phases of laryngeal tumorigenesis irrespective of p53 gene status and that TA-p63 mRNA down-regulation, but not p63 IR, may be clinically relevant in patients with LSCC.
Pruneri
Giancarlo
G
Division of Pathology and Laboratory Medicine, European Institute of Oncology and University of Milan School of Medicine, Milan, Italy.
Pignataro
Lorenzo
L
Manzotti
Michela
M
Carboni
Nadia
N
Ronchetti
Domenica
D
Neri
Antonino
A
Cesana
Bruno Mario
BM
Viale
Giuseppe
G
D000328:Adult; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018389:Codon, Nonsense; D017931:DNA Primers; D004268:DNA-Binding Proteins; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008207:Lymphatic Metastasis; D008565:Membrane Proteins; D008875:Middle Aged; D020125:Mutation, Missense; D010750:Phosphoproteins / Q000032:analysis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D013997:Time Factors; D015534:Trans-Activators / Q000032:analysis / Q000235:genetics*; D014157:Transcription Factors; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins
C081876:CKAP4 protein, human; D018389:Codon, Nonsense; D017931:DNA Primers; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins