Green Salad Intake Is Associated with Improved Oral Cancer Survival and Lower Soluble CD44 Levels.

Deficiencies in fruit and vegetable intake have been associated with oral cancer (oral cavity and oropharyngeal). Salivary rinses contain measurable biomarkers including soluble CD44 (solCD44) and total protein, which are known markers of oral cancer risk. This study investigates the effect of nutritional factors on solCD44 and protein levels to evaluate oral cancer risk and survival. We evaluated solCD44 and protein levels from 150 patients with oral and oropharyngeal squamous cell carcinoma and 150 frequency-matched controls. We subsequently characterized the effect of food group consumption and these biomarkers on progression-free survival (PFS) and overall survival (OS). Patients reported eating fewer servings of salad (p = 0.015), while controls reported eating fewer servings of potatoes (p < 0.001). Oral cancer patients who consumed at least one serving per week of green salad were found to have significantly lower CD44 levels than those who ate salad less frequently (mean of log2[solCD44]1.73 versus 2.25, p = 0.014). Patients who consumed at least one serving per week of "salad or other vegetables" had significantly longer PFS (median 43.5 versus 9.1 months, p = 0.003, adjusted hazard ratio (HR) = 0.39 p = 0.014) and OS (median 83.6 versus 10 months, p = 0.008, adjusted HR = 0.04 p = 0.029). These findings suggest that dietary factors, namely greater green salad and vegetable intake, may be associated with lower CD44 levels and better prognosis in oral cancer patients.

Disparities in Head and Neck Cancer: A Case for Chemoprevention with Vitamin D.

Blacks experience disproportionate head and neck cancer (HNC) recurrence and mortality compared to Whites. Overall, vitamin D status is inversely associated to HNC pointing to a potential protective linkage. Although hypovitaminosis D in Blacks is well documented it has not been investigated in Black HNC patients. Thus, we conducted a prospective pilot study accessing vitamin D status in newly diagnosed HNC patients stratified by race and conducted in vitro studies to investigate mechanisms associated with potential cancer inhibitory effects of vitamin D. Outcome measures included circulating levels of vitamin D, related nutrients, and risk factor characterization as well as dietary and supplemental estimates. Vitamin D-based in vitro assays utilized proteome and microRNA (miR) profiling. Nineteen patients were enrolled, mean circulating vitamin D levels were significantly reduced in Black compared to White HNC patients, 27.3 and 20.0 ng/mL, respectively. Whites also supplemented vitamin D more frequently than Blacks who had non-significantly higher vitamin D from dietary sources. Vitamin D treatment of HNC cell lines revealed five significantly altered miRs regulating genes targeting multiple pathways in cancer based on enrichment analysis (i.e., negative regulation of cell proliferation, angiogenesis, chemokine, MAPK, and WNT signaling). Vitamin D further altered proteins involved in cancer progression, metastasis and survival supporting a potential role for vitamin D in targeted cancer prevention.

Ethical surgical triage of patients with head and neck cancer during the COVID-19 pandemic.

BACKGROUND: Coronavirus has serially overtaken our metropolitan hospitals. At peak, patients with acute respiratory distress syndrome may outnumber mechanical ventilators. In our Miami Hospital System, COVID-19 cases have multiplied for 4 weeks and elective surgery has been suspended. METHODS: An Otolaryngologic Triage Committee was created to appropriately allocate resources to patients. Hospital ethicists provided support. Our tumor conference screened patients for nonsurgical options. Patients were tested twice for coronavirus before performing urgent contaminated operations. N95 masks and protective equipment were conserved when possible. Patients with low-grade cancers were advised to delay surgery, and other difficult decisions were made. RESULTS: Hundreds of surgeries were canceled. Sixty-five cases screened over 3 weeks are tabulated. Physicians and patients expressed discomfort regarding perceived deviations from standards, but risk of COVID-19 exposure tempered these discussions. CONCLUSIONS: We describe the use of actively managed surgical triage to fairly balance our patient's health with public health concerns.

Effect of actionable somatic mutations on racial/ethnic disparities in head and neck cancer prognosis.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and minorities have the worst survival. However, the molecular mechanisms underlying survival disparities have not been elucidated. METHODS: In a retrospective study, we assessed association between HNSCC early death (<2 years) and 208 somatic mutations of 10 cancer-related genes in 214 patients: 98 non-Hispanic whites (46%), 72 Hispanic whites (34%), and 44 African Americans (20%). RESULTS: Hispanic whites and African Americans had significantly higher mutation rates for EGFR, HRAS, KRAS, and TP53. HNSCC early death was significantly associated with 3+ mutations (odds ratio [OR] = 2.78, 95% confidence interval [CI] = 1.16, 6.69), NOTCH1 mutations in non-Hispanic whites (OR = 5.51; 95% CI = 1.22-24.83) and TP53 mutations in Hispanic whites (OR = 3.84; 95% CI = 1.08-13.68) in multivariable analysis adjusted for age, sex, tumor site, and tumor stage. CONCLUSION: We have provided the proof-of-principal data to link racial/ethnic-specific somatic mutations and HNSCC prognosis and pave the way for precision medicine to overcome HNSCC survival disparities. © 2016 Wiley Periodicals, Inc. Head Neck 38:1234-1241, 2016.

Risk Stratification System for Oral Cancer Screening.

Oral cavity and oropharyngeal cancer (oral cancer) is a deadly disease that is increasing in incidence. Worldwide 5-year survival is only 50% due to delayed intervention with more than half of the diagnoses at stage III and IV, whereas earlier detection (stage I and II) yields survival rates up to 80% to 90%. Salivary soluble CD44 (CD44), a tumor-initiating marker, and total protein levels may facilitate oral cancer risk assessment and early intervention. This study used a hospital-based design with 150 cases and 150 frequency-matched controls to determine whether CD44 and total protein levels in oral rinses were associated with oral cancer independent of age, gender, race, ethnicity, tobacco and alcohol use, and socioeconomic status (SES). High-risk subjects receiving oral cancer prevention interventions as part of a community-based program (n = 150) were followed over 1 year to determine marker specificity and variation. CD44 ≥5.33 ng/mL was highly associated with case status [adjusted OR 14.489; 95% confidence interval (CI), 5.973-35.145; P < .0001, vs. reference group CD44 <2.22 ng/mL and protein <1.23 mg/mL]. Total protein aided prediction above CD44 alone. Sensitivity and specificity in the frequency-matched study was 80% and 48.7%, respectively. However, controls were not representative of the target screening population due, in part, to a high rate of prior cancer. In contrast, specificity in the high-risk community was 74% and reached 95% after annual retesting. Simple and inexpensive salivary CD44 and total protein measurements may help identify individuals at heightened risk for oral cancer from the millions who partake in risky behaviors. Cancer Prev Res; 9(6); 445-55. ©2016 AACR.

CD44 interacts with EGFR and promotes head and neck squamous cell carcinoma initiation and progression.

OBJECTIVES: CD44 is a promising target for therapy in head and neck squamous cell carcinoma (HNSCC) and has two defined roles in tumorigenesis: it is a cancer stem cell (CSC) marker and it promotes migration and proliferation through interaction with many signaling molecules. The purpose of this study was to investigate the role of CD44 in HNSCC carcinogenesis. MATERIALS AND METHODS: The effects of CD44 in cell proliferation, migration, apoptosis and cisplatin resistance were studied by its overexpression in HNSCC cells. We also evaluated the effect of CD44 on tumor progression by siRNA methodology, immunohistochemistry (IHC) and western blot analysis. CD44 and EGFR colocalization were examined in CAL 27 cells by laser scanning confocal microscopy. The interaction between CD44 and EGFR was analyzed by immunoprecipation. RESULTS: Overexpression of CD44 enhances cell proliferation and migration and correlates with increased cisplatin resistance and apoptosis inhibition in SCC25 cells. Downregulation of CD44 in CAL27 cells inhibited constitutive EGFR phosphorylation and significantly reduced tumor growth in nude mice. CD44 and EGFR colocalized in CAL 27 cells. CD44 coimmunoprecipated with EGFR in CAL 27 cells, indicating that these proteins interact with each other. CONCLUSION: CD44 therapy in HNSCC may target the CSC population and alter EGFR signaling.

Salivary protein and solCD44 levels as a potential screening tool for early detection of head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a devastating disease usually diagnosed at a late stage when cure rates are 40%. We examined a simple and inexpensive molecular tool that may aid HNSCC detection. METHODS: Building on prior findings that total protein levels are elevated in 102 HNSCC cases versus 84 control subjects, we further analyzed these levels with respect to important risk and demographic variables and compared the results to soluble CD44 (solCD44). Using multivariate adaptive regression splines (MARSs)-logit modeling and logistic regression, we determined whether total protein, solCD44, or the combination best identifies HNSCC. RESULTS: Combined higher levels of solCD44 and protein were significantly associated with HNSCC (odds ratio [OR] = 24.90; 95% confidence interval [CI], 9.04-68.57; area under the curve [AUC] = 0.786). A model including protein plus solCD44 resulted in a better area (AUC 0.796) than either marker alone. CONCLUSION: Oral rinse levels of solCD44 and protein seem to hold promise for detection of HNSCC.

Perceived social support as a predictor of disease-specific quality of life in head-and-neck cancer patients.

BACKGROUND: Treatment for head-and-neck cancer (HNC) can lead to severe decrements in disease-specific quality of life (DSQOL) due to disfigurement and disability in speech, eating, and/or breathing. Psychosocial factors such as social support may explain individual variance in DSQOL outcomes. OBJECTIVE: The researchers sought to evaluate changes in perceived availability of social support from pretreatment to posttreatment and to determine whether decreases in perceived social support predicted poorer posttreatment DSQOL among HNC patients, controlling for disease- and treatment-related factors. METHODS: Participants (n = 32) were newly diagnosed with HNC and were awaiting surgery and/or radiation treatment. Measures included the ENRICHD Social Support instrument (ESSI) to assess perceived social support and the Functional Assessment of Cancer Therapy-Head & Neck (FACT-H&N) to assess DSQOL. Paired-samples t-tests and hierarchical regression analyses were conducted to determine relationships between pretreatment and posttreatment perceived social support and DSQOL. RESULTS: Perceived social support decreased significantly from pre- to posttreatment (F[31] = -2.71, P < .01). After adjusting for relevant covariates and pretreatment DSQOL, change in perceived social support remained a significant predictor of posttreatment DSQOL (ß = .47, P < .01). LIMITATIONS: This study included a relatively small sample of HNC patients, which limited power to evaluate mechanisms of observed relationships. CONCLUSIONS: Increased social isolation may be a risk factor for poorer physical recovery from, or adjustment to, treatment-related side effects. Social support may be an important target for psychosocial interventions for patients who face challenging treatment side effects.

Salivary markers and risk factor data: a multivariate modeling approach for head and neck squamous cell carcinoma detection.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a debilitating and deadly disease largely due to late stage diagnosis. Prior work indicates that soluble CD44 (solCD44) and total protein may be useful diagnostic markers for HNSCC. In this study we combine the markers solCD44, IL-8, HA, and total protein with demographic and risk factor data to derive a multivariate logistic model that improves HNSCC detection as compared to our previous data using biomarkers alone. METHODS: We performed the solCD44, IL-8, HA, and total protein assays on oral rinses from 40 HNSCC patients and 39 controls using ELISA assays. Controls had benign diseases of the upper aerodigestive tract and a history of tobacco or alcohol use. All subjects completed a questionnaire including demographic and risk factor data. RESULTS: Depending on cancer subsite, differences between cases and controls were found for all markers. A multivariate logistic model including solCD44, total protein and variables related to smoking, oral health and education offered a significant improvement over the univariate models with an AUC of 0.853. Sensitivity ranged from 75-82.5% and specificity from 69.2-82.1% depending on predictive probability cut points. CONCLUSION: A multivariate model, including simple and inexpensive molecular tests in combination with risk factors, results in a promising tool for distinguishing HNSCC patients from controls. IMPACT: In this case-control study, the resulting observations led to an unprecedented multivariate model that distinguished HNSCC cases from controls with better accuracy than the current gold standard which includes oral examination followed by tissue biopsy. Since the components are simple, noninvasive, and inexpensive to obtain, this model combining biomarkers, risk factor and demographic data serves as a promising prototype for future cancer detection tests.

Biomarkers Predict p53 Gene Therapy Efficacy in Recurrent Squamous Cell Carcinoma of the Head and Neck.

PURPOSE: Most recurrent squamous cell carcinomas of the head and neck have a dysfunctional p53 tumor suppressor pathway contributing to treatment resistance. We hypothesized that tumor p53 biomarkers may predict the efficacy of normal p53 delivered by gene therapy in these patients. EXPERIMENTAL DESIGN: Tumor p53 biomarkers were evaluated in 116 patients, including 29 treated with methotrexate in a phase III randomized controlled trial. Profiles favorable for p53 gene therapy efficacy were hypothesized to have either normal p53 gene sequences or low-level p53 protein expression, whereas unfavorable p53 inhibitor profiles were predicted to have high-level expression of mutated p53 that can inhibit normal p53 protein function. RESULTS: A statistically significant increase in tumor responses was observed for patients with favorable p53 efficacy profiles compared with those with unfavorable p53 inhibitor profiles [phase I/II trials: favorable (34 of 46, 74%) versus unfavorable (1 of 5, 20%), P = 0.0290; phase III trial: favorable (17 of 24, 71%) versus unfavorable (2 of 11, 18%), P = 0.0088]. In the phase III trial, there was statistically significant increased time to progression (TTP) and survival following p53 gene therapy in patients with favorable p53 profiles compared with unfavorable p53 inhibitor profiles (median TTP, 2.7 months versus 1.4 months, P = 0.0121; median survival, 7.2 months versus 2.7 months, P < 0.0001). In contrast, the biomarker profiles predictive of p53 gene therapy efficacy did not predict methotrexate response, TTP, or survival outcomes. CONCLUSIONS: These results indicate that tumor p53 biomarker profiles may predict p53 gene therapy efficacy in recurrent squamous cell carcinoma of the head and neck. (Clin Cancer Res 2009;15(24):7719-25).

Alcohol and tobacco use prediagnosis and postdiagnosis, and survival in a cohort of patients with early stage cancers of the oral cavity, pharynx, and larynx.

As more people begin to survive first cancers, there is an increased need for science-based recommendations to improve survivorship. For survivors of head and neck cancer, use of tobacco and alcohol before diagnosis predicts poorer survival; however, the role of continuing these behaviors after diagnosis on mortality is less clear, especially for more moderate alcohol consumption. Patients (n = 264) who were recent survivors of early stage head and neck cancer were asked to retrospectively report their tobacco and alcohol histories (before diagnosis), with information prospectively updated annually thereafter. Patients were followed for an average of 4.2 years, with 62 deaths observed. Smoking history before diagnosis dose-dependently increased the risk of dying; risks reached 5.4 [95% confidence interval (95% CI), 0.7-40.1] among those with >60 pack-years of smoking. Likewise, alcohol history before diagnosis dose-dependently increased mortality risk; risks reached 4.9 (95% CI, 1.5-16.3) for persons who drank >5 drinks/d, an effect explained by beer and liquor consumption. After adjusting for prediagnosis exposures, continued drinking (average of 2.3 drinks/d) postdiagnosis significantly increased risk (relative risk for continued drinking versus no drinking, 2.7; 95% CI, 1.2-6.1), whereas continued smoking was associated with nonsignificantly higher risk (relative risk for continued smoking versus no smoking, 1.8; 95% CI, 0.9-3.9). Continued drinking of alcoholic beverages after an initial diagnosis of head and neck cancer adversely affects survival; cessation efforts should be incorporated into survivorship care of these patients.

African American and poor patients have a dramatically worse prognosis for head and neck cancer: an examination of 20,915 patients.

BACKGROUND: Differences in cancer survival based on race, ethnicity, and socioeconomic status (SES) are a major issue. To identify points of intervention and improve survival, the authors sought to determine the impact of race, ethnicity, and socioeconomic status for patients with cancers of the head and neck (HN). METHODS: HN cancer patients diagnosed between 1998 and 2002 were examined using a linked Florida Cancer Data System and Florida Agency for Health Care Administration data set. RESULTS: A total of 20,915 patients with HN cancers were identified, predominantly in the oral cavity and larynx. Overall, 72% of patients were male, 89.7% were white, 8.4% were African American (AA), and 10.6% were Hispanic. The median survival time (MST) was 37 months. MST varied significantly by race (white, 40 months vs AA, 21 months; P < .001), sex (men, 36 months vs women, 41 months; P = .001), and area poverty level (lowest, 27 months vs highest, 34 months; P < .0001). Only 32% of AA patients underwent surgery in comparison with 45% of white patients (P < .001). On multivariate analysis, independent predictors of poorer outcomes were race, poverty, age, sex, tumor site, stage, grade, treatment modality, and a history of smoking and alcohol consumption. CONCLUSIONS: Carcinomas of the HN have an overall high mortality with a disproportionate impact on AA patients and the poor. Dramatic disparities by race and SES are not explained completely by demographics, comorbid conditions, or undertreatment. Earlier diagnosis and greater access to surgery and adjuvant therapies in these patients would likely yield significant improvement in outcomes.

Management of the neck in Merkel cell carcinoma of the head and neck: University of Miami experience.

BACKGROUND: We reviewed management of the cervical lymph nodes in patients with Merkel cell carcinoma (MCC) of the head and neck. METHODS: Records of 15 patients with MCC of the head and neck area were evaluated for the type of surgical treatment, including wide local excision, sentinel lymph node (SLN) biopsy, neck dissection, postoperative radiation therapy, and clinical outcomes. RESULTS: Median follow-up was 24 months (range, 5-84 months). Ten patients were treated with wide local excision plus SLN, with or without neck dissection. Five patients were treated with wide local excision only or wide local excision plus neck dissection. One patient died of distant metastases (7%), and 14 patients remain alive (93%), over a mean follow-up of 24 months. CONCLUSION: Wide excision and SLN biopsy for primary MCC with N0 neck is feasible for early-stage, previously untreated lesions. SLN biopsy was helpful in determining the nodal levels to be dissected or irradiated.

Unequal burden of head and neck cancer in the United States.

BACKGROUND: Black Americans are adversely affected by many types of malignancies. METHODS: We reviewed data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program to evaluate racial disparities in head and neck cancer incidence, mortality, and survival. RESULTS: Head and neck cancer incidence is greater in the black population and peaks at a younger age. The incidence disparity is decreasing over time and is less for cancers of the oral cavity/pharynx (OCP) than for cancers of the larynx. The disparity in survival after diagnosis is substantial for both sites and is increasing over time because of improvement in survival for the white population, but not for the black population. Some, but not all, of the survival disparity is due to more advanced stage at the time of diagnosis within the black population. The age-adjusted mortality rate for black men is approximately twice the rate for white men. CONCLUSION: Black Americans clearly bear a greater burden from head and neck cancer. The underlying causes are largely unknown, but are most likely due to a complex interplay of differences in access to health care, quality of medical care, biologic/genetic factors, incidence of comorbid conditions, exposure to carcinogens, diet, and cultural beliefs. Prospective studies are needed to define the relative importance of these factors and to inform intervention strategies.

Soluble CD44 is a potential marker for the early detection of head and neck cancer.

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. RESULTS: Mean salivary solCD44 levels were 24.4 +/- 32.0 ng/mL for HNSCC patients (range, 0.99-201 ng/mL) and 9.9 +/- 16.1 ng/mL (range, 0.73-124 ng/mL) for the patients with benign disease (P < 0.0001). Depending on cutoff point and HNSCC site, sensitivity ranged from 62% to 70% and specificity ranged from 75% to 88%. Nine of 11 HNSCC and 0 of 10 controls with low solCD44 levels showed hypermethylation of the CD44 promoter. CONCLUSIONS: SolCD44 is elevated in the majority of HNSCC and distinguishes cancer from benign disease with high specificity. Whereas the solCD44 test lacks sensitivity by itself, methylation status of the CD44 gene seems to complement the solCD44 test. Our pilot data indicate that, together, these markers will detect HNSCC with very high sensitivity and specificity.

Characterization of CD44v3-containing isoforms in head and neck cancer.

Head and neck squamous cell carcinoma (HNSCC) is a debilitating and deadly disease that is only cured 50% of the time. A better understanding of the molecular mechanisms involved in HNSCC progression may lead to earlier detection and improved cure rates. CD44 is a ubiquitous transmembrane glycoprotein comprising a family of alternatively spliced isoforms involved in cell migration and cell proliferation. CD44 isoforms containing the variant 3 (v3) exon include a growth factor binding site and may be involved in tumor progression. To characterize CD44v3-containing isoforms expression in HNSCC we purified RNA from four HNSCC cell lines and performed RT-PCR using junction primer strategies followed by gel elecrophoresis. Cloning and sequencing of HNSCC cell line PCR products revealed two isoforms. One of these, CD44v3-10, has been previously described. The other isoform, CD44v3, has not been characterized in HNSCC tissues. To further study this isoform, we purified RNA from 19 HNSCC tissues, 7 normal margin tissues and 5 true normal tissues. Following reverse-transcription, we performed quantitative PCR using junction primers specific for CD44v3. Results show that HNSCC tumor tissues expressed mean CD44v3 levels that were elevated 4.5 times more than true normal tissues (p < 0.01). Mean CD44v3 values for HNSCC tumors were 0.43 +/- 0.44 while mean levels for true normal tissues were 0.10 +/- 0.11. Levels in tumor tissue did not vary significantly with tumor characteristics such as site, stage, prior treatment, or nodal status. In addition, to characterize the role of this molecule plays in tumor progression, we overexpressed CD44v3 in a HNSCC cell line. Our results indicate that although higher levels of CD44v3 did not affect the rate of proliferation, a significant increase in migration was observed. CD44v3 may provide a target for future diagnostic and therapeutic interventions for HNSCC.

Complete hypopharyngeal obstruction by mucosal adhesions: a complication of intensive chemoradiation for advanced head and neck cancer.

BACKGROUND: Severe swallowing dysfunction is the dominant long-term complication observed in patients treated for head and neck squamous cell carcinoma (HNSCC) with treatment protocols using intensive concurrent chemotherapy with radiation therapy (chemo/XRT). We identified a subset of these patients, who were seen with complete obstruction of the hypopharynx distal to the site of the primary cancer, and in whom we postulate that the obstruction was caused by separable mucosal adhesions rather than obliteration by a mature fibrous stricture. METHODS: Seven patients were referred to the senior author with a diagnosis of complete hypopharyngeal obstruction between 1992 and 2001. The diagnosis was confirmed by barium swallow imaging and/or endoscopy before referral in all patients. Patients underwent recanalization by passing a Jesberg esophagoscope under general anesthesia, followed by serial dilations and intensive swallowing therapy. Patient charts were reviewed retrospectively after institutional review board approval. RESULTS: All seven patients were successfully recanalized. No patient had a perforation or other significant complication related to the recanalization procedure or subsequent dilations. Five of the seven patients showed improvement in swallowing at some point after the initial procedure, but just two patients recovered sufficiently to have their gastrostomy tube removed permanently. CONCLUSIONS: We conclude that complete hypopharyngeal obstruction secondary to mucosal adhesions is one cause of gastrostomy tube dependence in patients who have been treated with chemo/XRT for HNSCC. It is a difficult problem to treat, but most patients can recover useful swallowing function without undergoing laryngectomy or major surgical reconstruction. The postulated pathophysiology has implications for prevention as well as treatment.

Primary carcinosarcoma of the helix of the ear.

We report our histologic and immunohistochemical findings in a rare case of cutaneous carcinosarcoma involving the helix of the ear. The tumor exhibited cellular features of both basal cell and squamous cell carcinoma and a malignant mesenchymal component that was consistent with malignant fibrous histiocytoma. The epithelial component exhibited a positive immunohistochemical reaction to cytokeratin and a negative reaction to vimentin, whereas the mesenchymal component showed a positive immunohistochemical reaction to vimentin and a negative reaction to cytokeratin. To the best of our knowledge, this is only the third reported case of a carcinosarcoma of the ear and the second case in which it developed on the helix.

Salivary soluble CD44: a potential molecular marker for head and neck cancer.

OBJECTIVE: Head and neck squamous cell carcinoma (HNSCC) is a debilitating disease which is cured only 50% of the time. If diagnosed early, survival rates could reach 80%, but there is currently no practical method for early detection. CD44 comprises a family of isoforms that, in certain tumors, are alternatively spliced and overexpressed in tissues and circulation. Here we examine salivary soluble CD44 (solCD44) expression in HNSCC patients and normal controls to determine its potential as a screening tool. METHOD: We did a solCD44 ELISA on saliva from 26 HNSCC patients, 10 normal volunteers, conditioned media (CM) of 4 HNSCC cell lines, and 1 CD44-negative cell line (COS-7). Western blot was done on CM from 2 HNSCC cell lines (UMSS11B and FaDu), COS-7, 3 HNSCC, and 2 normal saliva specimens to verify ELISA antibody specificity. SolCD44 levels were significantly elevated in HNSCC patients compared with normal controls (7.85 ng/mL for HNSCC patients and 1.09 ng/mL for normal controls, P < 0.001). RESULTS: The test detected 79% of mucosally invasive HNSCC using preliminary cutoff points. SolCD44 levels did not vary significantly with tumor size, stage, recurrence, history of radiation treatment, or tobacco and alcohol risk factors. A 65 to 75 kDa band, corresponding to solCD44, was detected in all of the HNSCC cell line CM and saliva whereas normal samples showed a fainter band or were undetectable. CONCLUSION: In this preliminary analysis, the salivary solCD44 ELISA seems to effectively detect HNSCC at all stages. Further study is indicated because early detection is clearly important in this disease.

Supplemental beta-carotene, smoking, and urinary F2-isoprostane excretion in patients with prior early stage head and neck cancer.

Supplemental beta-carotene has been shown to increase lung cancer risk in recent chemoprevention trials, especially in current smokers. Several possible mechanisms for this effect have been suggested based upon in vitro and animal studies, but mechanistic data from human studies to explain the excess risk are lacking. beta-Carotene has both antioxidant and prooxidant effects in vitro; therefore, we evaluated whether or not high-dose supplemental beta-carotene might have prooxidant effects in vivo, especially in current smokers taking high-dose supplemental beta-carotene for several years (median 4.0 yr). Urine samples (n = 55 total) were collected from both smokers and nonsmokers participating in a multiyear randomized chemoprevention trial of supplemental beta-carotene (50 mg/day) versus placebo. Samples were analyzed by GC/MS for total isoprostanes and for 8-iso-prostaglandin F2 (8-iso-PGF2), stable end products of lipid peroxidation in vivo. Smokers had higher levels of both total isoprostanes and 8-iso-PGF2. Smokers and nonsmokers randomized to beta-carotene had nonsignificantly lower concentrations of total isoprostanes and of 8-iso-PGF2 [mean +- SD 8-iso-PGF2/ml = 2.00 +- 1.72 (placebo smoker); 1.72 +- 1.66 (beta-carotene smoker); 1.22 +- 0.68 (placebo nonsmoker); 0.97 +- 0.62 (beta-carotene nonsmoker)]. These results indicate that supplemental beta-carotene, even when given at high doses for many years, does not have prooxidant effects in either smokers or nonsmokers, as measured by urinary excretion of F2-isoprostanes.