Levels and patterns of expression of hypoxia-inducible factor-1α, vascular endothelial growth factor, glucose transporter-1 and CD105 in adenoid cystic carcinomas with high-grade transformation.
OBJECTIVE
To compare the expression of proteins regulated by hypoxia between adenoid cystic carcinoma (ACC) with and without high-grade transformation (HGT).


RESULTS
In eight ACC-HGT and 18 ACC without HGT, expression of hypoxia-inducible factor-1 (HIF-1α), vascular endothelial growth factor (VEGF), glucose transporter-1 (GLUT-1) and microvascular density (MVD) by CD105 (a hypoxia-inducible protein expressed in angiogenic endothelial cells) was determined. Expression levels of HIF-1α and VEGF as well as CD105-MVD did not differ significantly between: (i) transformed and conventional areas (TA and CA, respectively) of ACC-HGT, (ii) CA and ordinary ACC. HIF-1α was detected in 100% of cases and presented a diffuse expression pattern. No significant association was found between levels of HIF-1α expression and tumour size, metastasis and recurrence. GLUT-1 showed a prostromal expression pattern and was observed exclusively in TA (three of six cases) and in only three of 14 ACC.


CONCLUSIONS
Both the absence of significant alterations in levels of expression of HIF-1α, VEGF and CD105 and the patterns of expression of HIF-1α and GLUT-1 suggest that hypoxia may not play a key role in the process of high-grade transformation of ACC. Although HIF-1α expression is a common finding in ACC, it cannot be used as a marker of tumour aggressiveness.
Department of Pathology, University of Campinas/UNICAMP, Campinas, Brazil.
Ana F
AF
Costa
Marcelo G
MG
Tasso
Fernanda V
FV
Mariano
Andresa B
AB
Soares
Carlos T
CT
Chone
Agricio N
AN
Crespo
Manuel F
MF
Fresno
Jose L
JL
Llorente
Carlos
C
Suárez
Vera C
VC
de Araújo
Mario
M
Hermsen
Albina
A
Altemani
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D003528:Carcinoma, Adenoid Cystic / Q000378:metabolism* / Q000401:mortality / Q000628:therapy; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D003131:Combined Modality Therapy; D000071063:Endoglin; D005260:Female; D051272:Glucose Transporter Type 1 / Q000378:metabolism*; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000628:therapy; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D055815:Young Adult
D015703:Antigens, CD; D014408:Biomarkers, Tumor; C064206:ENG protein, human; D000071063:Endoglin; D051272:Glucose Transporter Type 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011956:Receptors, Cell Surface; D042461:Vascular Endothelial Growth Factor A