CXC chemokine receptor 4 is expressed in uveal malignant melanoma and correlates with the epithelioid-mixed cell type.
OBJECTIVE
Although relatively rare, uveal melanoma is the most common ocular tumor of adults. Up to half of uveal melanoma patients die of metastatic disease. CXCR4, a chemokine receptor, is a prognostic factor in cutaneous melanoma involved in angiogenesis and metastasis formation. The aim of this study was to evaluate the expression of CXCR4 in uveal melanoma.


METHODS
CXCR4 was detected by immunohistochemistry in 44 samples of uveal melanoma. Staining was categorized into three semiquantitative classes based on the rate of stained (positive) tumor cells: absence of staining, <50% of cell (+) and >50% (++). Correlations between CXCR4 expression, data on patient and tumor features were studied by contingency tables and the chi2 test. Time-to-event curves were studied using the Kaplan-Meier method. Univariate analysis was performed using the log-rank test. Ninety-five percent confidence intervals (95% CI) of hazard ratios were also reported.


RESULTS
Staining for CXCR4 protein was absent in 18 tumors (40.9%), present in <50% of cells in 19 (43.2%) and in >50% of cells in 7 (15.9%) tumors. CXCR4 expression correlated to the epithelioid-mixed cell type (P=0.030). No statistically significant relation emerged between CXCR4 expression, largest tumor diameter (LTD) and extracellular matrix patterns as evaluated through histological patterns stained with periodic acid-Schiff (PAS). Events occurred in 2 out of 18 patients (11.1%) with negative tumors (2 deaths), in 3 out of 19 patients (15.8%) with <50% of positive tumor cells (2 deaths and 1 occurrence of metastases) and in 1 out of 7 patients (14.3%) with >50% of positive tumor cells (1 occurrence of metastases). The cell type (P=0.0457) but not CXCR4 showed prognostic value at univariate analysis.


CONCLUSIONS
This study shows that CXCR4 is commonly expressed in uveal melanoma and correlates with cell type a well-established prognostic factor.
Scala
Stefania
S
Department of Clinical Immunology, National Cancer Institute, G. Pascale Foundation, via Mariano Semmola, 80131, Naples, Italy. scalaste@unina.it
Ieranò
Caterina
C
Ottaiano
Alessandro
A
Franco
Renato
R
La Mura
Anna
A
Liguori
Giuseppina
G
Mascolo
Massimo
M
Staibano
Stefania
S
Ascierto
Paolo A
PA
Botti
Gerardo
G
De Rosa
Gaetano
G
Castello
Giuseppe
G
D014408:Biomarkers, Tumor / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000175:diagnosis* / Q000473:pathology; D011379:Prognosis; D019718:Receptors, CXCR4 / Q000032:analysis*; D014604:Uveal Neoplasms / Q000175:diagnosis* / Q000473:pathology
D014408:Biomarkers, Tumor; D019718:Receptors, CXCR4