Molecular profiling using tissue microarrays as a tool to identify predictive biomarkers in laryngeal cancer treated with radiotherapy.
OBJECTIVE
To explore the usefulness of the expression of five potential cancer biomarkers in predicting outcome in patients with laryngeal cancer.


METHODS
In the present study, the Swedish National Cancer Registry databases were used to identify patients with laryngeal cancer diagnosed during the years 1978-2004 in the Uppsala-Orebro region and treated with radiotherapy. The expression of Ki-67, MutS homolog 2, (MSH2), p53, B-cell CLL/lymphoma 2 (Bcl-2) and cyclin D1 in the cancer cells was assessed immunohistochemically using tissue microarrays (TMAs) and its predicitve value on survival and relapse was analyzed using Cox regression models.


RESULTS
A total of 39 patients were included in the present study. Nuclear MSH2 staining was statistically significantly correlated to Ki-67 expression (p=0.022). However, univariate and multivariate Cox analyses showed no statistically significant association between the expression of the investigated biomarkers and overall survival or relapse.


CONCLUSIONS
The present exploratory study does not show any significant predictive value of the biomarkers examined with respect to survival or relapse. However, with larger patient cohorts, we believe that protein profiling using TMAs and immunohistochemistry is a feasible strategy for prognostic and predictive biomarker screening in laryngeal cancer.
Holgersson
Georg
G
Department of Oncology, Uppsala University Hospital, Sweden.
Ekman
Simon
S
Reizenstein
Johan
J
Bergqvist
Michael
M
Pontén
Fredrik
F
Uhlén
Mattias
M
Magnusson
Kristina
K
Jonnalagadda
Pallavi
P
Asplund
Anna
A
Strömberg
Sara
S
Linder
Arne
A
Blomquist
Erik
E
Liljeholm
Martin
M
Lödén
Britta
B
Hellström
Karin
K
Bergström
Stefan
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000096:biosynthesis; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000378:metabolism* / Q000532:radiotherapy; D019938:Cyclin D1 / Q000032:analysis / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis / Q000096:biosynthesis; D007822:Laryngeal Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D051718:MutS Homolog 2 Protein / Q000032:analysis / Q000096:biosynthesis; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000096:biosynthesis; D012008:Recurrence; D046888:Tissue Array Analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000096:biosynthesis
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; D051718:MutS Homolog 2 Protein