Transforming growth factor beta1 (TGFbeta1) expression in head and neck squamous cell carcinoma patients as related to prognosis.
BACKGROUND
Transforming growth factor beta1 (TGFbeta1) is a negative growth regulator in keratinocytes, and in vitro studies lead to the concept that loss of TGFbeta1 responsiveness is a critical step in epithelial carcinogenesis.


OBJECTIVE
To investigate the prognostic relevance of TGFbeta1 expression in head and neck squamous cell carcinoma (HNSCC).


METHODS
TGFbeta1 distribution was determined by immunohistochemistry in oral cavity/oropharynx (n = 79), larynx (n = 36) and hypopharynx (n = 25) tumors and in matched normal adjacent mucosa. TGFbeta-type I and II receptors were determined in 20 cases of differentiated oral cavity/hypopharynx tumors. Cases were considered positive if displaying reactivity in >10% of the cells.


RESULTS
TGFbeta1-positive expression was found in 47.2% of larynx, 36.7% of oral cavity/oropharynx and in 24% of the hypopharynx tumors. Reactivity in >60% of the cells was displayed only by 11.4% of HNSCC. All normal controls were positive. TGFbeta1-positive expression did not correlate with clinico pathological parameters. An association with differentiation was verified only in oral cavity/oropharynx tumors (P </= 0.001). TGFbeta1 was also not related to 5 years survival (Kaplan-Meier). Strong and diffuse expression of TGFbeta-RII was identified in 19/20 cases regardless of TGFbeta1 immunoreactivity. Out of 17 TGFbeta1-positive oral cavity/oropharynx tumors, only nine expressed TGFbeta-RI suggesting a disruption of the TGFbeta1 pathway. We conclude that TGFbeta1 protein immunostaining is not a useful biomarker in assessment of prognosis in HNSCC.
Logullo
Angela F
AF
Departamento de Radiologia, Disciplina de Oncologia da Faculdade de Medicina da USP, São Paulo, SP, Brazil.
Nonogaki
Suely
S
Miguel
Roberto E
RE
Kowalski
Luiz P
LP
Nishimoto
Inês N
IN
Pasini
Fátima S
FS
Federico
Miriam H H
MH
Brentani
Ricardo R
RR
Brentani
M Mitzi
MM
D030201:Activin Receptors, Type I / Q000032:analysis; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000473:pathology*; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000473:pathology; D007150:Immunohistochemistry; D007822:Laryngeal Neoplasms / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000473:pathology; D009959:Oropharyngeal Neoplasms / Q000473:pathology; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000032:analysis; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis; D015996:Survival Rate; D016212:Transforming Growth Factor beta / Q000032:analysis* / Q000235:genetics; D053773:Transforming Growth Factor beta1
D014408:Biomarkers, Tumor; D018125:Receptors, Transforming Growth Factor beta; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II