Chemokine receptor CXCR4 mRNA expression may be a marker of the presence of compromised lymph nodes in oral cavity squamous cell carcinoma

Abstract

9622 Background: Chemokine receptors have recently been shown to be involved in metastasis and in this work, we aimed to investigate which receptors CXCR1–5, CCR7 and CX3CR1 may correlate with the spread of Head and Neck Squamous cell cancer to regional lymph nodes. Methods: Chemokine receptor expression were analyzed in 61 fragments of primary tumor (T) and normal tumor adjacent mucosa (M) of 61 patients (pts) with operable HNSCC, by using the Ribonuclease Protection Assay (Riboquant RPA system, Pharmingen. These data, as expressed by densitometry relative to L32 internal control, and of 17 grossly compromised lymph nodes (LN) were correlated with clinical-pathological parameters by using t-paired test. Results: Primary tumors (T) as compared to normal tumor adjacent mucosa (N), (n=61), displayed a higher CXCR1 mRNA expression as expressed by densitometry relative to L32 internal control (Tumor: 0.010 ± 0.020 vs 0.004 ± 0.007: Normal, p=0.039) and a tendency to a higher CXCR3 (T: 0.007 ± 0.012 vs 0.004 ± 0.008:N, p=0.084) and CXCR4 (T: 0.198 ± 0,170 vs 0.156 ± 0.224: N, p=0.088). When oral primary site was individualized, we observed a significant increase in the CXCR4 mRNA expression in primary tumors as compared to normal tissue (T: 0.177 ± 0,117 vs 0.093 ± 0.088:N, p=0.004, n=18). In addition, we did not find diferences between pN0 (n=22) vs pN+ (n=30) primary tumors in the whole group, even though oral subgroup presented higher higher CXCR4 mRNA densitometric values in pN+ pts (0,224 ± 0,119, n=11) as compared to pN0 tumors (0,112 ± 0.081, n=8, p = 0,026, t-test paired). When available compromised lymph nodes (L) were studied, we have found higher CXR4, CXR5, CCR7 and CX3CR1 as compared to matched primary tumors: CXCR4 (L:0.400 ± 0,226 vs 0.182 ± 0.124:T, p=0.001, n=17), CXCR5 (L:0.040 ± 0,038 vs 0.004 ± 0.008:T, p=0.001, n=17), CCR7 (L:0.066 ± 0,067 vs 0.006 ± 0.011:T, p=0.002, n=17), and CX3CR1 (L:0.037 ± 0,036 vs 0.006 ± 0.009:T, p=0.002, n=17). No other differences were found. Conclusions: Among the chemokine receptors here studied, CXCR4 seems to play a role in lymph node spread of HNSCC, at least in oral cavity carcinoma. Further studies are warranted in this area to confirm these results. No significant financial relationships to disclose.