PubMed · 2589770
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
M Bettez, M D Maves, K D Dolan, W T Yuh. 1989. Maxillary sinus neoplasm.. https://doi.org/10.1177/000348948909801213
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
We previously reported a novel association between CDKN2A nonpromoter methylation and transcription (ARF/INK4a) in human papillomavirus associated oropharyngeal tumors. In this study we assessed whether nonpromoter CDKN2A methylation in laryngeal squamous cell carcinomas (LXSCC) conferred a similar association with transcription that predicted patient outcome. We compared DNA methylation and ARF/INK4a RNA expression levels for the CDKN2A locus using the Illumina HumanMethylation27 beadchip and RT-PCR in 43 LXSCC tumor samples collected from a prospective study of head and neck cancer patients treated at Montefiore Medical Center (MMC). Validation was performed using RNAseq data on 111 LXSCC tumor samples from the Cancer Genome Atlas (TCGA). The clinical relevance of combined nonpromoter CDKN2A methylation and transcription was assessed by multivariate Cox regression for locoregional recurrence on a subset of 69 LXSCC patients with complete clinicopathologic data from the MMC and TCGA cohorts. We found evidence of CDKN2A nonpromoter hypermethylation in a third of LXSCC from our MMC cohort, which was significantly associated with increased ARF and INK4a RNA expression (Wilcoxon rank-sum, P = 0.007 and 0.003, respectively). A similar association was confirmed in TCGA samples (Wilcoxon rank-sum test P < 0.0001 for ARF and INK4a). Patients with CDKN2A hypermethylation or high ARF/INK4a expression were significantly less likely to develop a locoregional recurrence compared to those with neither of the features, independent of other clinicopatholgic risk factors (adjusted hazard ratio=0.21, 95% confidence interval:0.05-0.81). These results support the conclusion that CDKN2A nonpromoter methylation is associated with increased ARF and INK4a RNA expression, and improved locoregional control in LXSCC.
To prospectively evaluate the prognostic significance of TP53, H-, K-, and N-Ras mutations, DNA-ploidy and S-phase fraction (SPF) in patients affected by locally advanced laryngeal squamous cell carcinoma (LSCC). Eight-one patients (median follow-up was 71 months) who underwent resective surgery for primary operable locally advanced LSCC were analyzed. Tumor DNA was screened for mutational analysis by PCR/SSCP and sequencing. DNA-ploidy and SPF were performed by flow cytometric analyses. Thirty-six patients (44%) had, at least, a mutation in the TP53 gene. Of them, 22% (8/36) had double mutations and 3% (1/36) had triple mutations. In total, 46 TP53 mutations were observed. The majority (41%) of these occur in exon 5 (19/46), while the mutations in exons 6, 7, and 8 were represented in 14, 7, and 6 patients, respectively (31%, 15%, and 16%). Five LSCC patients (6%) showed a mutation in H-Ras gene. Sixty-three percent of the cases (51/81) were DNA aneuploidy, 14% of these (7/51) were multiclonal. Thirty-nine patients (48%) had an high SPF value. At Univariate analysis, the DNA aneuploidy, high SPF (>15.1%), TP53 mutations and, in particular, the mutations that occur in exons 5 and 8 were significantly related to quicker disease relapse and short OS. At Multivariate analysis, the major significant predictors for both disease relapse and death were high SPF and any TP53 mutations. While histological grade G3 was an independent factor only for relapse. In conclusions, any TP53 mutations and high SPF are important biological indicators to predict the outcome of LSCC patients.
BACKGROUND: Endoscopic laser resection is one treatment modality for early glottic carcinoma. Benefits are the preservation of laryngeal structure without tracheotomy, the short duration of treatment, low traumatisation and good functional results. METHODS: From 1989 to 1999, 143 patients with an isolated and previously untreated glottic squamous cell carcinoma were treated by CO2 endoscopic laser resection. The tumors were classified as carcinoma in situ (Tis) in seven cases, T1 tumor (T1N0M0) in 91 patients and T2 tumor (T2N0M0) in 45 cases. Median follow-up was 5 years. RESULTS: For the group of Tis and T1 carcinomas, 86 of 98 patients were free of recurrences. The 12 recurrences (12.2%) were treated by repeated laser surgery and laryngectomy (four patients). None of these patients died of tumor related causes. For patients with T2 carcinomas, the overall recurrence rate was 28.9% (13 patients). In six patients, a total laryngectomy had to be performed and one patient died because of tumor recurrence. The relapse free survival estimate using the Kaplan-Meier method was 87% for Tis and T1 carcinomas and 70% for T2 carcinomas. The overall laryngeal preservation rate was 95% for Tis and T1 carcinomas and 85% for T2 tumors. All recurrences occurred within 4 years of primary surgery. CONCLUSION: The results suggest that the oncological outcome after endoscopic laser surgery is comparable to conventional open partial resections.