To analyze the impact of resection margin status and histologic prognosticators on local recurrence (LR) and overall survival (OS) for patients with oral squamous cell carcinoma (OSCC). This study was both retrospective and prospective in design. Cohort 1 refers to the entire group of 292 patients with OSCC. The slides from the earliest resection specimens from Cohort 1 were examined in an exploratory manner for multiple parameters. Cohort 2 refers to a subset of 203 patients, who did not receive any neoadjuvant therapy and had outcome data. Cohort 3 represents a subset of Cohort 2 (n = 168) wherein the histologic resection margin status could be reconfirmed. Cohort 4 refers a subset of 85 patients with tongue/floor of mouth tumors. Margin status was designated as follows: group 1, clearance of > or =5 mm with intraoperative analysis, no need for supplemental margins (n = 46); group 2, initial margins were measured as <5 mm during intraoperative frozen section; supplemental resection margins were negative on final pathology (n = 73); group 3, the final pathology revealed resection margins <5 mm (n = 30); group 4, the final pathology revealed frankly positive resection margins (n = 19). The endpoints of LR and OS were queried with respect to T stage, tumor site, margin status, and numerous histologic variables, by Cox regression and Kaplan-Meier survival analyses. Tumor stage (T) was significantly associated with LR (P = 0.028). Kaplan-Meier analysis for stage and for intraoral site was significantly associated with LR for T4 tumors. The increased likelihood of LR was higher for T4 OSCC of the buccal mucosa (75%), sinopalate (50%), and gingiva (100%) compared with mobile tongue (27%), and oropharynx (13%) (P = 0.013). Margin status was not associated with LR or OS (Cohort 3). This was so when all tumors were grouped together and when separate analyses were performed by tumor stage and oral subsite. No significance was demonstrated when margin status was examined for patients with similar treatment (surgery alone or surgery with adjuvant RT). However, the administration of adjuvant RT did significantly increase local disease-free survival (P = 0.0027 and P = 0.001 for T1 and T2 SCC, respectively). On exploratory analyses of histologic parameters, worst pattern of invasion was significantly associated with LR (P = 0.015) and OS (P < 0.001). Perineural invasion involving large nerves (>1 mm) was associated with LR (P = 0.005) and OS (P = 0.039). Limited lymphocytic response was also significantly associated with LR (P = 0.005) and OS (P = 0.001). When used as covariates in a multivariate Cox regression model, worst pattern of invasion, perineural invasion, and lymphocytic response were significant and independent predictors of both LR and OS, even when adjusting for margin status. Thus, these factors were used to generate our risk assessment. Our risk assessment classified patients into low-, intermediate-, or high-risk groups, with respect to LR (P = 0.0004) and OS (P < 0.0001). This classification retained signific...

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor and possesses a high incidence of 10p loss. The KLF6 (Kruppel-like transcription factor) tumor suppressor gene on 10p15 is inactivated by loss of heterozygosity (LOH) and/or somatic mutation in a number of human cancers and forced expression of KLF6 in GBM lines inhibits their growth and transformation. In addition, increased expression of its alternatively spliced, cytoplasmic isoform KLF6-SV1 has now been shown to play a role in cancer pathogenesis. On the basis of these findings we examined the role of KLF6 and KLF6-SV1 in the development and progression of GBM. LOH analysis of 17 primary GBM patient samples using KLF6-specific microsatellite markers revealed that 88.2% (15/17) had LOH of the KLF6 locus. Interestingly, no KLF6 somatic mutations were identified. RNA analysis revealed concomitant decreases in all primary GBM tumors (n 5 11) by~80% in KLF6 expression (p < 0.001) coupled with increased KLF6-SV1 expression (p < 0.001) when compared to normal astrocytes. To determine the biological relevance of these findings, we examined the effect of KLF6 expression and KLF6-SV1 knockdown in A235 and CRL2020 cell lines. Reconstitution of KLF6 decreased cell proliferation by almost 50%, whereas targeted KLF6 reduction increased cell proliferation 2.5-4.5 fold. Conversely, targeted KLF6-SV1 reduction decreased cell proliferation by 50%. Taken together, our findings demonstrate that KLF6 allelic imbalance and decreased KLF6 and increased KLF6-SV1 expression are common findings in primary GBM tumors, and these changes have antagonistic effects on the regulation of cellular proliferation in GBM cell lines. ' 2007 Wiley-Liss, Inc.Key words: KLF6; KLF6-SV1; GBM; LOH Glioblastoma multiforme (GBM) is both the most frequent and aggressive primary brain tumor. 1 Despite efforts to develop strategies for earlier diagnosis and improved treatment regimens combining radiotherapy and chemotherapy, the average relative survival rates remain less than 43% at 6 months, 18% at 1 year and 3% at 2 years. 2 Therefore, a critical need exists to define the genetic pathways underlying the development of this cancer.Loss of heterozygosity (LOH) on chromosome 10 is one of the most consistent genetic alterations in the development and progression of glioblastoma. Interestingly, LOH of 10p has been shown to be restricted to primary glioblastoma. [3][4][5][6] The tight linkage of complete or partial deletions of 10p to malignant progression of glioblastoma suggests the direct involvement of a critical tumor suppressor gene in this locus. Although growth suppression has been observed after microcell mediated transfer of chromosome fragments from 10p14-15 into T98G glioblastoma cells 4 the putative tumor suppressor gene at this locus has not yet been identified.The Kruppel-like transcription factor (KLF6) gene is a tumor suppressor that maps to 10p15.1 and has been reported by us and others to be dysregulated and inactivated by loss or somatic mutation in a numbe...

Objective Compare the accuracy of the Eustachian Tube Dysfunction Questionnaire-7 (ETDQ-7) in identifying people with Eustachian tube (ET) dysfunction based on symptoms and based on an objective ET function test. Study Design Cross-sectional study. Setting Tertiary referral center. Subjects and Methods 55 subjects with and without symptoms suggestive of ET dysfunction completed the ETDQ-7 questionnaire and had their ET function evaluated by the percentage of middle ear pressure equilibrated after 5 swallows (PEq5) either during a Pressure Chamber test (intact tympanic membranes) or by the Inflation-Deflation test (non-intact tympanic membranes). The ETDQ-7 score ≥ 14.5 and PEq5<60% were used to define ET dysfunction and sensitivity, specificity and Receiver Operating Characteristic curves were used to assess the level of association between ETDQ-7 scores and PEq5. Results 25 asymptomatic (Group 1= 15 females, 15 whites, mean age 32±12.8 years) and 30 subjects with ET dysfunction symptoms (Group 2= 17 females, 25 whites, mean age 27±16.3 years) were included in the analysis. ETDQ-7 sensitivity and specificity regarding correct group assignment were 70% and 100% and with respect to predicting PEq5<60%, 54% and 78% respectively. An area under the curve (AUC) of 0.68 (95% CI 0.53–0.83) at the participant level and of 0.64 (95% CI 0.50–0.77) at ear level indicated a moderate level of association which was lower, although not statistically significant, for non-intact tympanic membranes (AUC=0.63 at participant and AUC=0.49 at ear level). Conclusion The ETDQ-7 score had higher correlation with ET dysfunction symptoms than with an objective measure of ET function.

This methodology has application in developing quantitative descriptions of ET mechanics in groups of persons without and with history or suspected ET dysfunction. A lesser degree of soft palate elevation during swallow that derives the ET medial lamina rotation and widening of the ET orifice may be associated with poor ET function and higher risk for otitis media. Videoendoscopic evaluation of the ET orifice may assist in diagnosing presence and mechanism of ET dysfunction.