No detectable hypoxia in malignant salivary gland tumors: preliminary results.
OBJECTIVE
Hypoxia is detected in most solid tumors and is associated with malignant progression and adverse treatment outcomes. However, the oxygenation status of malignant salivary gland tumors has not been previously studied. The aim of this study was to investigate the potential clinical relevance of hypoxia in this tumor type.


METHODS
Twelve patients scheduled for surgical resection of a salivary gland tumor were preoperatively injected with the hypoxia marker pimonidazole and the proliferation marker iododeoxyuridine. Tissue samples of the dissected tumor were immunohistochemically stained for blood vessels, pimonidazole, carbonic anhydrase-IX, glucose transporters-1 and -3 (Glut-1, Glut-3), hypoxia-inducible factor-1alpha, iododeoxyuridine, and epidermal growth factor receptor. The tissue sections were quantitatively assessed by computerized image analysis.


RESULTS
The tissue material from 8 patients was of sufficient quality for quantitative analysis. All tumors were negative for pimonidazole binding, as well as for carbonic anhydrase-IX, Glut-1, Glut-3, and hypoxia-inducible factor-1alpha. The vascular density was high, with a median value of 285 mm(-2) (range, 209-546). The iododeoxyuridine-labeling index varied from <0.1% to 12.2% (median, 2.2%). Epidermal growth factor receptor expression levels were mostly moderate to high. In one-half of the cases, nuclear expression of epidermal growth factor receptor was observed.


CONCLUSIONS
The absence of detectable pimonidazole binding, as well as the lack of expression of hypoxia-associated proteins in all tumors, indicates that malignant salivary gland tumors are generally well oxygenated. It is unlikely that hypoxia is a relevant factor for their clinical behavior and treatment responsiveness.
Wijffels
Karien I E M
KI
Department of Otorhinolaryngology, Head and Neck Surgery, Deventer Hospital, Deventer, The Netherlands.
Hoogsteen
Ilse J
IJ
Lok
Jasper
J
Rijken
Paulus F J W
PF
Marres
Henri A M
HA
de Wilde
Peter C M
PC
van der Kogel
Albert J
AJ
Kaanders
Johannes H A M
JH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000032:analysis; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000032:analysis; D015687:Cell Hypoxia; D049109:Cell Proliferation; D003857:Deoxyuridine / Q000031:analogs & derivatives; D051272:Glucose Transporter Type 1 / Q000032:analysis; D051273:Glucose Transporter Type 2 / Q000032:analysis; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis; D008875:Middle Aged; D009593:Nitroimidazoles / Q000378:metabolism; D012468:Salivary Gland Neoplasms / Q000098:blood supply / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology
D000951:Antigens, Neoplasm; D051272:Glucose Transporter Type 1; D051273:Glucose Transporter Type 2; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009593:Nitroimidazoles; C033815:pimonidazole; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; D003857:Deoxyuridine