Correlation of gene methylation in surgical margin imprints with locoregional recurrence in head and neck squamous cell carcinoma.

BACKGROUND: Securing negative surgical margins is a critical goal for head and neck surgery. Local recurrence develops even in some patients who have histologically negative surgical margins. Minimal residual tumor cells may lead to locoregional recurrence despite clear histologic margins reported at the time of resection of head and neck squamous cell carcinoma (HNSCC). To identify subclinical residual disease, the authors analyzed deep margin imprint samples collected on 1-layer nitrocellulose sheets. METHODS: Bisulfite-treated DNA samples from 73 eligible patients were amplified by quantitative methylation-specific polymerase chain reaction (QMSP) targeting 6 genes (deleted in colorectal cancer [DCC], endothelin receptor type B [EDNRB], homeobox protein A9 [HOXA9], kinesin family member 1A [KIF1A], nidogen-2 [NID2], and N-methyl D-aspartate receptor subtype 2B [NR2B]). QMSP values were dichotomized as positive or negative. Associations between the QMSP status of deep margin samples and clinical outcomes were evaluated. RESULTS: Two-gene methylation combinations among the genes DCC, EDNRB, and HOXA9 were associated with decreased locoregional recurrence-free survival, recurrence-free survival, and overall survival. The methylated gene combination of EDNRB and HOXA9 in margin imprints was the most powerful predictor of poor locoregional recurrence-free survival (hazard ratio [HR], 3.31; 95% confidence interval [CI], 1.30-8.46; P = .012) independent of standard histologic factors. In addition, methylation of both EDNRB and HOXA9 indicated a trend toward reduced recurrence-free survival (HR, 2.74; 95% CI, 0.90-8.33; P = .075) and reduced OS (HR, 5.78; 95% CI, 0.75-44.7; P = .093) in multivariable analysis. CONCLUSIONS: A panel of gene methylation targets in deep surgical margin imprints provides a potential predictive marker of postoperative locoregional recurrence. Intraoperative use of molecular margin imprint analysis may assist surgeons in obtaining rigorously negative surgical margins and improve the outcome of head and neck surgery.

Innovative rapid gene methylation analysis of surgical margin tissues in head and neck cancer.

BACKGROUND: Securing the negative surgical margin is the first step in surgical cancer treatment. However, tumor recurrence sometimes occurs even with histologically negative surgical margins. To detect minimal residual cancer cells in the deep margin intraoperatively, a time-efficient molecular approach is required. METHODS: We established an innovative rapid quantitative methylation PCR (QMSP) assay, which consists of substantially time-minimized DNA extraction, bisulfite treatment, and QMSP assays. To demonstrate the feasibility of this procedure, 10 serial surgical specimens of primary head and neck squamous cell carcinoma (HNSCC) were evaluated by both rapid and conventional QMSP. Two frequently methylated genes in head and neck cancer, homeobox A9 (HOXA9) and endothelin receptor type B (EDNRB) were analyzed in 10 HNSCCs and surgical margin tissues, as well as normal muscle and oral mucosa samples. RESULTS: The product quality of DNA extraction and bisulfite treatment using the time-saving procedure was comparable to the conventional procedure. In the QMSP assay, target gene methylation and reference gene methylation were equally detected by both the rapid and conventional method. Finally, relative results of rapid and conventional QMSP were quite similar to each other in tumors, margins, and normal tissues. The average total time required for the rapid QMSP procedure was less than 3 h and could be accomplished by a single person. CONCLUSION: From the viewpoint of accuracy, cost, and time consumption, the innovative rapid QMSP maintains highly sensitive methylation detection accomplished within the time frame of a major ablative and reconstructive procedure.

Postpartum depression screening by family nurse practitioners.

PURPOSE: The purpose of the study was to identify whether and how nurse practitioners (NPs) screen for postpartum depression, as well as to identify factors affecting such screening. DATA SOURCES: Self-report data were gathered from 159 questionnaires completed by a convenience sample of family NPs (FNPs) in Illinois and Wisconsin during July 2002. CONCLUSIONS: Despite the fact that 84% of FNP respondents saw at least one postpartum woman yearly, 42% never screened for postpartum depression in any way. The subjects' confidence in their knowledge of how to use a screening tool was the single best predictor of screening behavior (r= .487). NPs tend to follow clinical practice guidelines, but no guidelines exist to address postpartum depression specifically. Screening for postpartum depression is not universal, making it likely that prevailing estimates of the incidence of this disease are low. IMPLICATIONS FOR PRACTICE: If the number of NPs who screen for postpartum depression could be increased, many postpartum patients and families could be positively affected. Advanced practice nursing education should adequately prepare graduates to screen at-risk patients. The development of graduate curricula including thorough units on postpartum depression, as well as formulation of clinical practice guidelines for postpartum depression, could make great strides toward more and better screening, prompt diagnosis, and treatment.