Perineural invasion of small nerves is associated with an increased risk of local recurrence and cervical metastasis and is, independent of extracapsular spread, a predictor of survival for patients with SCC of the upper aerodigestive tract.

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Breast and kidney-expressed chemokine (BRAK) CXCL14 is a new CXC chemokine with unknown function and receptor selectivity. The majority of head and neck squamous cell carcinoma (HNSCC) and some cervical squamous cell carcinoma do not express CXCL14 mRNA, as opposed to constitutive expression by normal oral squamous epithelium. In this study, we demonstrate that the loss of CXCL14 in HNSCC cells and at HNSCC primary tumor sites was correlated with low or no attraction of dendritic cell (DC) in vitro, and decreased infiltration of HNSCC mass by DC at the tumor site in vivo. Next, we found that recombinant human CXCL14 and CXCL14-positive HNSCC cell lines induced DC attraction in vitro, whereas CXCL14-negative HNSCC cells did not chemoattract DC. Transduction of CXCL14-negative HNSCC cell lines with the human CXCL14 gene resulted in stimulation of DC attraction in vitro and increased tumor infiltration by DC in vivo in chimeric animal models. Furthermore, evaluating the biologic effect of CXCL14 on DC, we demonstrated that the addition of recombinant human CXCL14 to DC cultures resulted in up-regulation of the expression of DC maturation markers, as well as enhanced proliferation of allogeneic T cells in MLR. Activation of DC with recombinant human CXCL14 was accompanied by up-regulation of NF-κB activity. These data suggest that CXCL14 is a potent chemoattractant and activator of DC and might be involved in DC homing in vivo.

Purpose: To determine the effect of tyrosine-phosphorylated signal transducer and activator of transcription 3 (pSTAT3) immunoexpression on survival in two independent cohorts of patients with squamous cell carcinoma of the head and neck (SCCHN) and to evaluate pSTAT3, transforming growth factor-a (TGF-a), epidermal growth factor receptor (EGFR), and gastrin-releasing peptide receptor (GRPR) expression in matched tumor and lymph node metastases in one of these cohorts. Experimental Technique: Immunostaining for pSTAT3, TGF-a, EGFR, and GRPR was done in two SCCHN cohorts (cohort 1, 61 tumors; cohort 2, 69 paired primary tumors and lymph node metastases). Semiquantitative scores derived from the product of staining intensity (scale 0-3) score and percentage of positive tumor cells were correlated with clinical outcome. Results: Immunoexpression of pSTAT3 did not correlate with clinical outcome in either cohort (cohort 1, P = 0.914; cohort 2, P = 0.312). In cohort 2,TGF-a and EGFR expression in the primary tumors showed some association with decreased disease-free survival (P = 0.0306 and P = 0.0985, respectively). Both pSTAT3 and EGFR showed a correlation of expression between tumor and matched lymph node metastasis (P < 0.0001 and P = 0.0046, respectively). In addition, the expression of EGFR and GRPR in the primary tumors correlated withTGF-a expression in paired nodal metastases (P = 0.0043 and P = 0.0268, respectively). In the nodal metastases, TGF-a expression correlated with EGFR expression (P = 0.0069). In primary tumors, GRPR expression correlated withTGF-a and EGFRexpression (P = 0.0378 and P = 0.0026, respectively). Conclusions: These findings support an autocrine signaling pathway involving TGF-a, EGFR, and pSTAT3 in metastatic SCCHN as well as transactivation of EGFR by GRPR viaTGF-a, but fails to identify an independent prognostic role for pSTAT3 immunoexpression.

One case of an expansile mass involving the roots of a mandibular left first molar in a nine year old male is presented. The lesion has features of a cementoblastoma (CB), osteoblastoma (OB), and osteosarcoma (OS) both radiographically and histologically. Radiographically, a ''sunburst'' appearance is present. Histologically, the lesional tissue is intimately involved with the root, not the periosteum. The clinical, radiographic, and histopathologic characteristics of CB, OB, and OS are discussed as well as the difficulties associated with distinguishing between these lesions in the gnathic region.