p63 immunoreactivity in lung cancer: yet another player in the development of squamous cell carcinomas?
The p63 protein, a member of the p53 family of nuclear transcription factors, is characterized by different capabilities of transactivating reporter genes, inducing apoptosis, and functioning as dominant-negative agent. This study evaluated the prevalence and prognostic implications of p63 immunoreactivity in 221 patients with stage I non-small cell lung carcinoma (NSCLC) and in 57 patients with stage I-IV neuroendocrine tumours (NET). The results were correlated with the tumour proliferative fraction, the accumulation of p53 protein, and with patient survival. p63 immunoreactivity was seen in 109/118 squamous cell carcinomas, 15/95 adenocarcinomas, 2/2 adenosquamous carcinomas, 4/6 large cell carcinomas, 9/20 poorly differentiated NET, and 1/37 typical and atypical carcinoids (p < 0.001). Furthermore, the prevalence of p63-immunoreactive cells increased progressively from pre-neoplastic and pre-invasive lesions to invasive squamous cell carcinomas. In these latter tumours, but not in adenocarcinomas, p63 immunoreactivity correlated directly with the tumour proliferative fraction (p = 0.028), and inversely with the tumour grade (p = 0.004). No relationship was found with p53 protein immunoreactivity or the other clinico-pathological variables examined. Although p63 is likely to be involved in the development of pulmonary squamous cell carcinoma, it does not carry any prognostic implication for NSCLC patients.
Pelosi
Giuseppe
G
Department of Pathology and Laboratory Medicine, European Institute of Oncology and University of Milan School of Medicine, Milan, Italy. giuseppe.pelosi@ieo.it
Pasini
Felice
F
Olsen Stenholm
Catharina
C
Pastorino
Ugo
U
Maisonneuve
Patrick
P
Sonzogni
Angelica
A
Maffini
Fausto
F
Pruneri
Giancarlo
G
Fraggetta
Filippo
F
Cavallon
Alessandra
A
Roz
Elena
E
Iannucci
Antonio
A
Bresaola
Enrica
E
Viale
Giuseppe
G
D000230:Adenocarcinoma / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001980:Bronchi / Q000378:metabolism; D018278:Carcinoma, Neuroendocrine / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D004268:DNA-Binding Proteins; D018450:Disease Progression; D018572:Disease-Free Survival; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D011230:Precancerous Conditions / Q000378:metabolism; D012189:Retrospective Studies; D015996:Survival Rate; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
D014408:Biomarkers, Tumor; C081876:CKAP4 protein, human; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D010750:Phosphoproteins; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins