Introduction: Head and neck squamous cell carcinoma (HNSCC) is a devastating and deadly disease, largely because it is diagnosed in late stage. Cure rates, currently at 50%, could increase to >80% with early detection. In this study, we evaluate soluble CD44 (solCD44) as an early detection tool for HNSCC by determining whether it reliably distinguishes HNSCC from benign disease of the upper aerodigestive tract. Methods: We carried out the solCD44 ELISA on oral rinses from 102 patients with HNSCC and 69 control patients with benign diseases of upper aerodigestive tract to determine the sensitivity and specificity of the test for differentiating HNSCC from benign disease. Furthermore, we did a pilot study using methylation-specific PCR primers on oral rinses from 11 HNSCC patients with low solCD44 levels and 10 benign disease controls.

This series equals the largest pediatric series of HIV-associated parotid gland BLEC in the English literature. One patient in our series also demonstrated PGL; there were no cases of BLEL. A classification system based on morphology is proposed to help resolve the confusion in terminology used to describe this entity. Most pediatric HIV-infected patients with parotid gland BLEC can be treated with observation and antiretroviral medication therapy. For others, who are symptomatic or more concerned about their cosmetic appearance, sclerotherapy may offer a reasonable option. Radiation therapy and surgery should be reserved for select cases.

Purpose: To determine the nature and potential pharmacologic reversibility of deficient TP53 expression and function in head and neck squamous cell carcinomas (HNSCC) with wild-type TP53, previously associated with decreased sensitivity to cisplatin therapy. Experimental Design: TP53 genotype, mRNA and protein expression, TP53-induced p21 expression, and TP53 DNA^binding and reporter gene function were determined in a panel of nine previously characterized HNSCC cell lines from the University of Michigan squamous cell carcinoma (UM-SCC) series. The genotoxic drug doxorubicin and the anti-inflammatory and antimalarial drug quinacrine, previously identified as inducers of TP53, were used to examine the nature and potential reversibility of deficient TP53 expression and function. The specific role of inducibleTP53 on function and cellular proliferation was confirmed using selectiveTP53 inhibitor pifithrin-a or short hairpin RNA knockdown. The capability of quinacrine to sensitize HNSCC to the cytotoxic effects of cisplatin was assessed. Results: UM-SCC cell lines with wild-type TP53 genotype underexpressed TP53 mRNA and protein when compared with normal human keratinocytes or UM-SCC with mutant TP53. Although doxorubicin failed to induce TP53 expression or functional activity, quinacrine induced TP53 mRNA and protein expression, increased TP53 reporter activity and p21 protein expression, and induced growth inhibition in these wild-type TP53 cell lines. Quinacrineinduced TP53 reporter activity and growth suppression were attenuated by pifithrin-a and TP53 short hairpin RNA knockdown. Furthermore, quinacrine sensitized UM-SCC to cisplatin in vitro. Conclusions: Deficient TP53 mRNA and protein expression underlies decreased function in a subset of HNSCC with wild-type TP53 and can be restored together with cisplatin sensitization by quinacrine. TP53, a tumor suppressor gene important in regulating cellcycle arrest, apoptosis, and therapeutic sensitivity, represents one of the most common targets for alterations underlying the development of cancer, including head and neck squamous cell carcinomas (HNSCC; refs. 1 -5). Mutation of TP53 occurs in f40% to 50% of HNSCC, resulting in altered TP53 expression and function (3 -5). In HNSCC that retain wild-type TP53 genotype, approximately one half expressed detectable TP53 protein, whereas approximately one half exhibited deficient expression by immunohistochemistry (6). In the latter subset of HNSCC that retain wildtype TP53 genotype, the alterations resulting in a defect in TP53 expression or function have been shown to include protein inactivation after infection with human papilloma virus (HPV), defects of p16INK4a and other components of the DNA damage response pathway, or unknown mechanisms. As a consequence, the differing nature and effects of these multiple alterations on TP53 expression and function likely contributed to the frequent discordance of results between studies using immunohistochemistry, genotyping, or other methods to define the role of TP53 in...