CD44 expression predicts local recurrence after radiotherapy in larynx cancer.
OBJECTIVE
To find molecular markers from expression profiling data to predict recurrence of laryngeal cancer after radiotherapy.


METHODS
We generated gene expression data on pre-treatment biopsies from 52 larynx cancer patients. Patients developing a local recurrence were matched for T-stage, subsite, treatment, gender and age with non-recurrence patients. Candidate genes were then tested by immunohistochemistry on tumor material from a second series of 76 patients. Both series comprised early stage cancer treated with radiotherapy alone. Finally, gene expression data of eight larynx cancer cell lines with known radiosensitivity were analyzed.


RESULTS
Nineteen patients with a local recurrence were matched with 33 controls. Gene sets for hypoxia, proliferation and intrinsic radiosensitivity did not correlate with recurrence, whereas expression of the putative stem cell marker CD44 did. In a supervised analysis, probes for all three splice variants of CD44 on the array appeared in the top 10 most significantly correlated with local recurrence. Immunohistochemical analysis of CD44 expression on the independent validation series confirmed CD44's predictive potential. In 8 larynx cancer cell lines, CD44 gene expression did not correlate with intrinsic radiosensitivity although it did correlate significantly with plating efficiency, consistent with a relationship with stem cell content.


CONCLUSIONS
CD44 was the only biological factor tested which significantly correlated with response to radiotherapy in early stage larynx cancer patients, both at the mRNA and protein levels. Further studies are needed to confirm this and to assess how general these findings are for other head and neck tumor stages and sites.
de Jong
Monique C
MC
Department of Experimental Therapy, The Netherlands Cancer Institute, The Netherlands.
Pramana
Jimmy
J
van der Wal
Jacqueline E
JE
Lacko
Martin
M
Peutz-Kootstra
Carine J
CJ
de Jong
Jos M
JM
Takes
Robert P
RP
Kaanders
Johannes H
JH
van der Laan
Bernard F
BF
Wachters
Jasper
J
Jansen
Jeroen C
JC
Rasch
Coen R
CR
van Velthuysen
Marie-Louise F
ML
Grénman
Reidar
R
Hoebers
Frank J
FJ
Schuuring
Ed
E
van den Brekel
Michiel W
MW
Begg
Adrian C
AC
D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics* / Q000378:metabolism; D007822:Laryngeal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D046228:Microarray Analysis; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D014407:Tumor Cells, Cultured; D054928:Validation Studies as Topic
D014408:Biomarkers, Tumor; C497483:CD44 protein, human; D018960:Hyaluronan Receptors