Use of multiple biological markers in radiotherapy-treated head and neck cancer.
OBJECTIVE
Management of patients with head and neck squamous cell carcinoma is often based on clinical parameters, with little appreciation of the underlying tumour biology. Single biological marker studies fail to acknowledge the complexity of these tumours. Our aim was to define a profile of biological markers associated with outcome.


METHODS
This retrospective study involved consecutive patients with oropharyngeal squamous cell carcinoma treated with primary radiotherapy between 1996 and 2001. Pre-treatment biopsies were used to study the immunohistochemical expression of nine biological markers. Markers were chosen to reflect biologically relevant pathways.


RESULTS
Following analysis of nine markers, a profile of two markers was derived (carbonic anhydrase 9 and major vault protein), the co-expression of which conferred a significantly poor probability of locoregional control. The prognostic effect of these biomarkers in combination was greater than their effect individually.


CONCLUSIONS
Biomarker profiles can be established which highlight large differences in locoregional control. Identifying tumours that express both carbonic anhydrase 9 and major vault protein may facilitate patient selection for more aggressive treatment.
Silva
P
P
School of Cancer & Enabling Sciences, The University of Manchester, Manchester, UK.
Slevin
N J
NJ
Sloan
P
P
Valentine
H
H
Ryder
D
D
Price
P
P
West
Catharine M L
CM
Homer
J J
JJ
D017766:Acid Anhydride Hydrolases / Q000032:analysis; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000175:diagnosis* / Q000532:radiotherapy; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D051272:Glucose Transporter Type 1 / Q000032:analysis; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000032:analysis; D009959:Oropharyngeal Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000532:radiotherapy; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D012189:Retrospective Studies; D020394:Vault Ribonucleoprotein Particles / Q000032:analysis; D000099187:Major Vault Protein; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; D066246:ErbB Receptors; D051272:Glucose Transporter Type 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein; D000099170:Bis(5'-adenosyl)triphosphatase; C497442:HIF1A protein, human; C495677:SLC2A1 protein, human; C512478:EGFR protein, human; C089226:CA9 protein, human