Prognostic value of histamine H1 receptor expression in oral squamous cell carcinoma.
OBJECTIVE
Overexpression of the histamine H1 receptor (H1R) has been described in a variety of tumor models, but experience in oral squamous cell carcinomas (OSCC) is not available. Current adjuvant treatment options for OSCC can be improved by the identification of new targets of therapy. Herein, we evaluated H1R expression in a large patient cohort of OSCC.


METHODS
H1R immunoexpression was evaluated in 191 cases of OSCC and two OSCC cell lines BICR56 and BICR3. Scanned images were digitally analyzed using ImageJ and the immunomembrane plug-in. The combined score of computer-assisted semiquantitative analysis was correlated with manually counted percentages of tumor cells by Kendall's tau (т) correlation coefficient. Disease-free survival times were estimated using the Kaplan-Meier method and were compared by using the log-rank test. Multivariate analyses were performed using the Cox proportional hazards model.


RESULTS
H1R was rarely expressed in OSCC but significantly related with advanced tumor stages (n = 21/191, mean expression 63.5% of cancer cells in positive tumor samples, 95% confidence interval of the mean 53.5 to 73.6%, p = 0.006). Following univariate analysis, patients with H1R expression showed a significant poorer prognosis (p = 0.0004). Multivariate analysis revealed H1R expression as an independent prognostic factor (p = 0.0164). Expression of H1R in cancer cell lines was confirmed by specific staining of OSCC cell lines BICR56 and BICR3.


CONCLUSIONS
This is the first study focusing on H1R expression showing a significant poorer DFS rate in the H1R+ patient cohort. Based on these data, H1R activation may promote carcinogenesis in OSCC.


CONCLUSIONS
Investigation of H1R regulation and its antagonists shows a clear rationale for future supportive anticancer therapies in OSCCs.
Department of Oral and Maxillofacial Surgery, University Hospital Tuebingen, Osianderstrasse 2-8, 72076, Tuebingen, Germany. dr.dr.martingrimm@googlemail.com
Martin
M
Grimm
Michael
M
Krimmel
Dorothea
D
Alexander
Adelheid
A
Munz
Susanne
S
Kluba
Constanze
C
Keutel
Juergen
J
Hoffmann
Joachim
J
Polligkeit
Siegmar
S
Reinert
Sebastian
S
Hoefert
D014408:Biomarkers, Tumor; D063646:Carcinogenesis / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D011969:Receptors, Histamine H1 / Q000096:biosynthesis* / Q000235:genetics
D014408:Biomarkers, Tumor; D011969:Receptors, Histamine H1