Expression of p53 and its homologues in primary and recurrent squamous cell carcinomas of the head and neck.
The tumour-suppressor protein p53 belongs to a family that includes 2 structurally related proteins, p63 and p73. Because of their structural homology, it has been hypothesized that both homologues serve as "spare mechanisms" in p53 mutations to regulate the cell cycle by inducing apoptosis. We investigated the mutational and protein expression status of p53 in correlation to its homologues, p73 and p63, in primary and recurrent squamous cell carcinomas of the head and neck (HNSCC) and corresponding nonneoplastic mucosa. Expression and mutation of p53 and its homologues p63 (including the 2 major isotypes TAp63 and DeltaNp63) and p73 was examined by direct DNA sequencing and immunohistochemistry in 29 primary and 39 recurrent (secondary) HNSCCs after microdissection. Our results were correlated with pathohistologic stage and grade. p53 mutations were detected in 32/68 (47%) carcinomas of 17 patients, with a discordant mutation pattern of primary and consecutive tumours in all cases. Positive immunostaining for p63 was found in 55/68 (81%) carcinomas of 29 patients. Immunohistochemistry revealed p73 protein expression in 32/68 (47%) tumours. In normal mucosa, p63 and p73 were expressed in 40/68 (59%) and 12/68 (18%) cases, respectively. We failed to detect specific mutations of p73 or p63 in primary and recurrent carcinoma of the head and neck. p73 and p63 were rarely mutated in HNSCC, but both were expressed in a subset of tumours. The lack of correlation between p73/p63 and p53 protein expression suggests that neither p73 nor p63 can replace p53 when it is mutated.
Weber
Anette
A
Department of Otorhinolaryngology, Head and Neck Surgery, University of Leipzig, Leipzig, Germany. Anette.Weber@t-online.de
Bellmann
Ulf
U
Bootz
Friedrich
F
Wittekind
Christian
C
Tannapfel
Andrea
A
D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D008565:Membrane Proteins; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins
C081876:CKAP4 protein, human; D017931:DNA Primers; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C115051:TP63 protein, human; C000606460:TP73 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins