Expression of Bcl-2 family proteins and association with clinicopathological characteristics of oral squamous cell carcinoma.
OBJECTIVE
To characterize the expression of proteins that inhibit (Bcl-2, Bcl-x, Bcl-xL, Bcl-2-related protein A1, BAG-1) or promote (Bak, Bax, Bim/Bod, Bim-Long, Bad, Bid, PUMA) apoptosis and determine possible correlations between the expression of these proteins and clinicopathological features of oral squamous cell carcinoma (OSCC).


RESULTS
Two-hundred and twenty-nine cases of OSCC, arranged in a tissue microarray, were immunohistochemically analysed. The results demonstrated that the absence of vascular invasion was associated with increased expression of Bak, Bax, Bcl-xL, Bcl-2-related protein and PUMA. Increased expression of Bim/Bod and BAG-1 was associated with the presence of perineural infiltration. An increase in Bid and Bim-Long expression was associated with moderately to well-differentiated tumours. Increased expression of the Bcl-2-related protein and PUMA was associated with tumours occurring in the floor of mouth and increased expression of PUMA was also associated with recurrence of the tumour. Multivariate Cox analysis demonstrated that PUMA and Bim-Long were independent factors in prognosis of OSCC.


CONCLUSIONS
Our results showed the involvement of the Bcl-2 family of proteins in OSCC tumorigenesis and suggest that the expression of apoptotic molecules might be used as a prognostic indicator for OSCC.
Coutinho-Camillo
Cláudia Malheiros
CM
Department of Pathology, Hospital A.C. Camargo, Rua Professor Antonio Prudente 109 1 andar, Liberdade, São Paulo, Brazil. claumcc@terra.com.br
Lourenço
Silvia Vanessa
SV
Nishimoto
Ines Nobuko
IN
Kowalski
Luiz Paulo
LP
Soares
Fernando Augusto
FA
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D040081:Protein Array Analysis; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C494772:BAK1 protein, human; C494826:BAX protein, human; C438378:BBC3 protein, human; C091732:BCL2-associated athanogene 1 protein; C096816:BCL2-related protein A1; C494811:BCL2L1 protein, human; C000606775:BCL2L11 protein, human; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D000072224:Bcl-2-Like Protein 11; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D015778:Minor Histocompatibility Antigens; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014157:Transcription Factors; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein