Defining the Performance of Clinician's Ability to Screen for Laryngeal Mass From Voice.

OBJECTIVE: Defining a clinician's ability to perceptually identify mass from voice will inform the feasibility, design priorities, and performance standards for tools developed to screen for laryngeal mass from voice. This study defined clinician ability of and examined the impact of expertise on screening for laryngeal mass from voice. STUDY DESIGN: Task comparison study between experts and nonexperts rating voices for the probability of a laryngeal mass. SETTING: Online, remote. METHODS: Experts (voice-focused speech-language pathologists and otolaryngologists) and nonexperts (general medicine providers) rated 5-s/i/voice samples (with pathology defined by laryngoscopy) for the probability of laryngeal mass via an online survey. The intraclass correlation coefficient (ICC) estimated interrater and intrarater reliability. Diagnostic performance metrics were calculated. A linear mixed effects model examined the impact of expertise and pathology on ratings. RESULTS: Forty clinicians (21 experts and 19 nonexperts) evaluated 344 voice samples. Experts outperformed nonexperts, with a higher area under the curve (70% vs 61%), sensitivity (49% vs 36%), and specificity (83% vs 77%) (all comparisons p < .05). Interrater reliability was fair for experts and poor for nonexperts (ICC: 0.48 vs 0.34), while intrarater reliability was excellent and good, respectively (ICC: 0.9 and 0.6). The main effects of expertise and underlying pathology were significant in the linear model (p < .001). CONCLUSION: Clinicians demonstrate inadequate performance screening for laryngeal mass from voice to use auditory perception for dysphonia triage. Experts' superior performance indicates that there is acoustic information in a voice that may be utilized to detect laryngeal mass based on voice.

Intersectionality of Race, Ethnicity, and Gender in the Otolaryngology Match From 2013 to 2019.

OBJECTIVES: Racial, ethnic, and gender disparities in the otolaryngology-head and neck surgery (OHNS) match have been described individually, but not intersectionally. Intersectionality recognizes how multiple forms of discrimination (e.g., sexism, racism) can have a combined effect. The objective of this study was to analyze racial, ethnic, and gender disparities in the OHNS match using an intersectional approach. METHODS: Cross-sectional evaluation of data from otolaryngology applicants from the Electronic Residency Application Service (ERAS) and of corresponding otolaryngology residents from the Accreditation Council for Graduate Medical Education (ACGME) from 2013 to 2019. Data were stratified by race, ethnicity, and gender. The Cochran-Armitage tests assessed trends over time in the proportions of applicants and corresponding residents. Chi-square tests with Yates' continuity correction were performed to evaluate differences between the aggregate proportions of applicants and corresponding residents. RESULTS: The proportion of White men in the resident pool was increased compared to the applicant pool (ACGME 0.417, ERAS 0.375; Δ + 0.042; 95% CI 0.012 to 0.071; p = 0.03). This was also the case for White women (ACGME 0.206, ERAS 0.175; Δ + 0.031; 95% CI 0.007 to 0.055; p = 0.05). In contrast, there was a smaller proportion of residents compared to applicants among Multiracial men (ACGME 0.014, ERAS 0.047; Δ - 0.033; 95% CI -0.043 to -0.023; p < 0.001) and Multiracial women (ACGME 0.010, ERAS 0.026; Δ - 0.016; 95% CI -0.024 to -0.008; p < 0.001). CONCLUSION: The findings of this study imply that White men have a persistent advantage, while several racial, ethnic, and gender minorities are disadvantaged in the OHNS match. Further research is necessary to examine why these differences exist in residency selection, including evaluation during the screening, reviewing, interviewing, and ranking stages. Laryngoscope, 133:2558-2563, 2023.

The impact of the COVID-19 pandemic on medical student education: Implementation and outcome of a virtual general surgery curriculum.

BACKGROUND: Due to the COVID-19 pandemic, medical schools were forced to adapt clinical curricula. The University of Washington School of Medicine created a hybrid in person and virtual general surgery clerkship. METHODS: The third year general surgery clerkship was modified to a 4-week in person and 2-week virtual clerkship to accommodate the same number of learners in less time. All students completed a survey to assess the impact of the virtual clerkship. RESULTS: The students preferred faculty lectures over national modules in the virtual clerkship. 58.6% indicated they would prefer the virtual component before the in-person experience. There was no change from previous years in final grades or clerkship exam scores after this hybrid curriculum. CONCLUSIONS: If the need for a virtual general surgery curriculum arises again in the future, learners value this experience at the beginning of the clerkship and prefer faculty lectures over national modules.

Computer-Aided Rhinoplasty Using a Novel "navigated" Nasal Osteotomy Technique: A Pilot Study.

OBJECTIVE: To describe the surgical technique of navigation-guided nasal osteotomies and assess feasibility of this technique for treating complex nasal bone deformities in reconstructive rhinoplasty. METHODS: A retrospective chart review was performed in order to identify patients who underwent computer-aided rhinoplasty from August 2014 to February 2017. Inclusion criteria were nasal bone deformities on computed-tomography (CT) that correlated with specific nasal complaints. All patients underwent computer-aided rhinoplasty with navigation-guided nasal osteotomies using a standard navigation system. Osteotomies were performed using real-time visualization on the navigation screen. Additional soft tissue procedures were performed as needed. Medical records were reviewed for presenting symptoms, radiologic and operative findings, and postoperative course. Cosmetic outcomes were subjectively based on patients' standard 6-view photo-documentation from pre- and post-operative timepoints. RESULTS: Twenty-one patients were included in the study; 8 were revision cases and 3 had mild-to-moderate hemifacial microsomia. Fifteen were completely closed procedures. No cases were opened because of inadequate visualization or difficulty accessing bony pathology. Mean (range) follow up was 98.6 (6-559) days. There were no intra-operative complications, unplanned admissions or re-admissions, or iatrogenic cosmetic complications (ie, "inverted V" or "saddle nose" deformities). Two patients required revision. One was after suffering nasal trauma within 4 weeks of initial rhinoplasty. The second underwent further correction of a deformity that required a costochondral graft. Both experienced good final results. CONCLUSIONS: Computer-aided rhinoplasty is safe and feasible for treating complex nasal deformities using standard navigation systems.

Evidence of Specialty-Specific Gender Disparities in Resident Recruitment and Selection.

BACKGROUND: Specialty-specific gender disparities are multifactorial, yet one area that is lacking from this discussion is the impact of recruitment and selection. OBJECTIVE: Customized data reports were utilized to compare trends in the gender representation of applicants and residents within 11 surgical and medical specialties between 2013 and 2018. METHODS: Applicant data was obtained from the Electronic Residency Application Service (ERAS) and resident data from the Accreditation Council for Graduate Medical Education (ACGME). Eleven specialties with the highest number of applications per applicant were included (dermatology, emergency medicine, general surgery, neurological surgery, obstetrics and gynecology [OB/GYN], orthopedic surgery, otolaryngology, plastic surgery, radiation oncology, radiology, urology). A Cochran-Armitage trend test assessed for changes in the proportion of females within the total applicant group and the corresponding matched resident group. A t test was utilized to compare the mean proportion of females for ERAS and ACGME data. RESULTS: Otolaryngology, plastic surgery, radiation oncology, and urology had no significant changes over the study period. Dermatology, general surgery, and orthopedic surgery demonstrated increased gender diversity in applicants over time, while OB/GYN demonstrated decreased gender diversity. General surgery and neurological surgery showed increased gender diversity in resident representation over time. Emergency medicine and radiology had increased gender diversity, and OB/GYN had decreased gender diversity in matched residents compared to applicants. CONCLUSIONS: Our findings provide baseline data, but also illustrate evident gaps in our understanding and attempts to improve gender diversity. A multifaceted approach to obtaining and assessing data from all stages of residency recruitment and selection is necessary to support these efforts.

Does Attending Surgeon Presence at the Preinduction Briefing Improve Operating Room Efficiency?

OBJECTIVE: To examine if attending surgeon presence at the preinduction briefing is associated with a shorter time to incision. STUDY DESIGN: Retrospective cohort study and survey. SETTING: Tertiary academic medical center. SUBJECTS AND METHODS: A retrospective cohort study was conducted of 22,857 operations by 141 attending surgeons across 12 specialties between August 3, 2016, and June 21, 2018. The independent variable was attending surgeon presence at the preinduction briefing. Linear regression models compared time from room entry to incision overall, by service line, and by surgeon. We hypothesized a shorter time to incision when the attending surgeon was present and a larger effect for cases with complex surgical equipment or positioning. A survey was administered to evaluate attending surgeons' perceptions of the briefing, with a response rate of 68% (64 of 94 attending surgeons). RESULTS: Cases for which the attending surgeon was present at the preinduction briefing had a statistically significant yet operationally minor reduction in mean time to incision when compared with cases when the attending surgeon was absent. After covariate adjustment, the mean time to incision was associated with an efficiency gain of 1.8 ± 0.5 minutes (mean ± SD; P < .001). There were no statistically significant differences in the subgroups of complex surgical equipment and complex positioning or in secondary analysis comparing service lines. The surgeon was the strongest confounding variable. Survey results demonstrated mild support: 55% of attending surgeons highly prioritized attending the preinduction briefing. CONCLUSION: Attending surgeon presence at the preinduction briefing has only a minor effect on efficiency as measured by time to incision.

Comparison of Micro-Computed Tomography and Clinical Computed Tomography Protocols for Visualization of Nasal Cartilage Before Surgical Planning for Rhinoplasty.

IMPORTANCE: There is no imaging standard to model nasal cartilage for the planning of rhinoplasty procedures. Preoperative visualization of cartilage may improve objective evaluation of nasal deformities, surgical planning, and surgical reconstruction. OBJECTIVES: To evaluate the feasibility of visualizing nasal cartilage using high resolution micro-computed tomography (CT) compared with the criterion standard of pathologic findings in a cadaveric specimen and to evaluate its accuracy compared with various clinical CT protocols. DESIGN, SETTING, AND PARTICIPANTS: Anatomic study at the University of Washington using single human cadaveric nasal specimens performed from July 10, 2017, to March 30, 2018. INTERVENTIONS: A micro-CT acquisition with 60-micron resolution was obtained of a nasal specimen. The specimen was then scanned with 5 different clinical CT protocols to span both clinical care and machine limits. The specimen was then sectioned in 5-mm axial slices for pathologic analysis. MAIN OUTCOMES AND MEASURES: Micro-CT images were registered to pathologic specimen cross-sections using a graphite fiducial system. Cartilage substructures were manually segmented and analyzed. A library of matched images across the micro-CT and various clinical CT protocols was then developed. Region of interest analysis was performed for each of the cartilage structures and their boundaries on clinical CT protocols and micro-CT, with the outcome of mean (SD) density using Hounsfield units. RESULTS: A single human cadaveric nasal specimen was used to obtain the following results. Lower lateral cartilage, upper lateral cartilage, and septal cartilage were accurately delineated on the micro-CT images compared with pathologic findings. The mean absolute deviation from pathologic findings was 0.30 mm for septal cartilage thickness, 0.98 mm for maximal upper lateral cartilage length, and 1.40 mm for maximal lower lateral cartilage length. On clinical CT protocols, only septal cartilage was well discriminated from boundary. Higher radiation dose resulted in more accurate density measurements of cartilage, but it did not ultimately improve ability to discriminate cartilage. CONCLUSIONS AND RELEVANCE: The results of this anatomic study may represent a notable step toward advancing knowledge of the capabilities and pitfalls of nasal cartilage visualization on CT. Nasal cartilage visualization was feasible on the micro-CT compared with pathologic findings. Future research may further examine the barriers to accurately visualizing upper lateral cartilage and lower lateral cartilage, a prerequisite for clinical application. LEVEL OF EVIDENCE: NA.

Automated Surgical Approach Planning for Complex Skull Base Targets: Development and Validation of a Cost Function and Semantic At-las.

Successful multidisciplinary treatment of skull base pathology requires precise preoperative planning. Current surgical approach (pathway) selection for these complex procedures depends on an individual surgeon's experiences and background training. Because of anatomical variation in both normal tissue and pathology (eg, tumor), a successful surgical pathway used on one patient is not necessarily the best approach on another patient. The question is how to define and obtain optimized patient-specific surgical approach pathways? In this article, we demonstrate that the surgeon's knowledge and decision making in preoperative planning can be modeled by a multiobjective cost function in a retrospective analysis of actual complex skull base cases. Two different approaches- weighted-sum approach and Pareto optimality-were used with a defined cost function to derive optimized surgical pathways based on preoperative computed tomography (CT) scans and manually designated pathology. With the first method, surgeon's preferences were input as a set of weights for each objective before the search. In the second approach, the surgeon's preferences were used to select a surgical pathway from the computed Pareto optimal set. Using preoperative CT and magnetic resonance imaging, the patient-specific surgical pathways derived by these methods were similar (85% agreement) to the actual approaches performed on patients. In one case where the actual surgical approach was different, revision surgery was required and was performed utilizing the computationally derived approach pathway.

Anatomical Region Segmentation for Objective Surgical Skill Assessment with Operating Room Motion Data.

Background Most existing objective surgical motion analysis schemes are limited to structured surgical tasks or recognition of motion patterns for certain categories of surgeries. Analyzing instrument motion data with respect to anatomical structures can break the limit, and an anatomical region segmentation algorithm is required for the analysis. Methods An atlas was generated by manually segmenting the skull base into nine regions, including left/right anterior/posterior ethmoid sinuses, frontal sinus, left and right maxillary sinuses, nasal airway, and sphenoid sinus. These regions were selected based on anatomical and surgical significance in skull base and sinus surgery. Six features, including left and right eye center, nasofrontal beak, anterior tip of nasal spine, posterior edge of hard palate at midline, and clival body at foramen magnum, were used for alignment. The B-spline deformable registration was adapted to fine tune the registration, and bony boundaries were automatically extracted for final precision improvement. The resultant deformation field was applied to the atlas, and the motion data were clustered according to the deformed atlas. Results Eight maxillofacial computed tomography scans were used in experiments. One was manually segmented as the atlas. The others were segmented by the proposed method. Motion data were clustered into nine groups for every dataset and outliers were filtered. Conclusions The proposed algorithm improved the efficiency of motion data clustering and requires limited human interaction in the process. The anatomical region segmentations effectively filtered out the portion of motion data that are out of surgery sites and grouped them according to anatomical similarities.

Evaluation of a Minimally Disruptive Treatment Protocol for Frontal Sinus Fractures.

IMPORTANCE: Despite common goals of frontal sinus fracture treatment (restoring forehead contour and creating a safe sinus), there remains significant variability in evaluation and treatment. OBJECTIVE: To describe our experience with a minimally disruptive treatment protocol for the treatment of frontal sinus fractures. DESIGN, SETTING, AND PARTICIPANTS: Analysis of prospectively collected data from 2010 through 2015 at a level 1 trauma center. All patients with frontal sinus fractures treated with our protocol from January 2010 to December 2015. Patients with poor follow-up and/or incomplete medical records were excluded from analysis. MAIN OUTCOMES AND MEASURES: Presence of an aerated frontal sinus and aesthetically acceptable forehead contour. Secondary outcome measures were complications related to frontal sinus fractures. RESULTS: A total of 39 patients were treated under our minimally disruptive protocol, and 25 patients were included in the study; 18 (72%) were male and 7 (28%) were female. Their ages ranged from 6 to 62 years. After review, 22 patients had both clinical and radiographic follow-up. No patients underwent immediate frontal sinus repair. Five of 22 patients underwent surgery for indications other than their frontal sinus fracture: 1 of 5 patients underwent immediate surgical repair due to bilateral LeFort fractures, and 4 of 5 underwent delayed surgery due to nasal polyps (1 patient), scar revision (1 patient), and concomitant LeFort fractures (2 patients). Two of 22 patients (9%) underwent frontal sinus repair after outpatient surveillance due to persistent cerebrospinal fluid leak (1 patient) and orbital roof fracture (1 patient). The remaining 20 patients were treated nonoperatively, and 19 of 20 (95%) had spontaneous improvement in opacification and/or contour deformity. Twelve of 20 patients (60%) had improvement or resolution in both. One patient had ongoing partial opacification and deformity at the 3-month follow-up but was asymptomatic and had bony contour that was aesthetically acceptable to the patient. There were no complications. The median of all follow-up was 3 months. CONCLUSIONS AND RELEVANCE: Frontal sinus fractures treated nonoperatively had a high rate of spontaneous ventilation and bony autoreduction with aesthetically acceptable frontal bone remodeling. There were no complications in the nonoperative group. The initial results of this study support further study of the safety and efficacy of a minimally disruptive protocol for frontal sinus fractures. LEVEL OF EVIDENCE: 4.

A Bayesian Network Model of Head and Neck Squamous Cell Carcinoma Incorporating Gene Expression Profiles.

Radiation therapy allows precision targeting of certain groups of lymph nodes and is a treatment for metastatic head and neck squamous cell carcinoma. In current practice, there is approximately 15% probability that physicians inadvertently treat healthy tissue or leave the cancerous lymph nodes untreated. The aim of this work is to improve the accuracy of medical decision-making by extending existing predictive models to capture the probabilities of finding cancerous lymph nodes at each of the six image-based surgical neck level using a patient's genetic profile, primary tumor site and tumor size. Our model was trained with publicly available data extracted from the Cancer Genome Atlas (TCGA) and validated against the TCGA dataset both with and without genetic information. Results show that genetic profile data improves model accuracy. These findings suggest that our predictive model may improve the accuracy of clinical decision-making, especially for patients with more advanced metastasis. However, more data is needed to ensure significance of the proposed effects, as well as to improve accuracy of the overall model.

Endothelial and circulating C19MC microRNAs are biomarkers of infantile hemangioma.

Infantile hemangioma (IH) is the most common vascular tumor of infancy, and it uniquely regresses in response to oral propranolol. MicroRNAs (miRNAs) have emerged as key regulators of vascular development and are dysregulated in many disease processes, but the role of miRNAs in IH growth has not been investigated. We report expression of C19MC, a primate-specific megacluster of miRNAs expressed in placenta with rare expression in postnatal tissues, in glucose transporter 1-expressing (GLUT-1-expressing) IH endothelial cells and in the plasma of children with IH. Tissue or circulating C19MC miRNAs were not detectable in patients having 9 other types of vascular anomalies or unaffected children, identifying C19MC miRNAs as the first circulating biomarkers of IH. Levels of circulating C19MC miRNAs correlated with IH tumor size and propranolol treatment response, and IH tissue from children treated with propranolol or from children with partially involuted tumors contained lower levels of C19MC miRNAs than untreated, proliferative tumors, implicating C19MC miRNAs as potential drivers of IH pathogenesis. Detection of C19MC miRNAs in the circulation of infants with IH may provide a specific and noninvasive means of IH diagnosis and identification of candidates for propranolol therapy as well as a means to monitor treatment response.

Development of a Novel Markov Chain Model for the Prediction of Head and Neck Squamous Cell Carcinoma Dissemination.

Prediction of microscopic tumor spread to regional lymph nodes can assist in radiation planning for cancer treatment. However, it is still challenging to predict tumor spread. In this paper, we present a unique approach to modeling how tumor cells disseminate to form regional metastases. This involves leveraging well established knowledge resources and commonly held notions of how cancer spreads. Using patient data, we utilized our approach to create a model of metastasis for the subset of head and neck squamous cell carcinoma that arises in the mucosa of the lateral tongue. The model was created using a training set extracted from the clinical records of 50 patients with tumors of this type who presented to the University of Washington head and tumor board over a three and half year period. The test sets consist of four case series drawn from the literature.

Biological Model Development as an Opportunity to Provide Content Auditing for the Foundational Model of Anatomy Ontology.

Constructing a biological model using an established ontology provides a unique opportunity to perform content auditing on the ontology. We built a Markov chain model to study tumor metastasis in the regional lymphatics of patients with head and neck squamous cell carcinoma (HNSCC). The model attempts to determine regions with high likelihood for metastasis, which guides surgeons and radiation oncologists in selecting the boundaries of treatment. To achieve consistent anatomical relationships, the nodes in our model are populated using lymphatic objects extracted from the Foundational Model of Anatomy (FMA) ontology. During this process, we discovered several classes of inconsistencies in the lymphatic representations within the FMA. We were able to use this model building opportunity to audit the entities and connections in this region of interest (ROI). We found five subclasses of errors that are computationally detectable and resolvable, one subclass of errors that is computationally detectable but unresolvable, requiring the assistance of a content expert, and also errors of content, which cannot be detected through computational means. Mathematical descriptions of detectable errors along with expert review were used to discover inconsistencies and suggest concepts for addition and removal. Out of 106 organ and organ parts in the ROI, 8 unique entities were affected, leading to the suggestion of 30 concepts for addition and 4 for removal. Out of 27 lymphatic chain instances, 23 were found to have errors, with a total of 32 concepts suggested for addition and 15 concepts for removal. These content corrections are necessary for the accurate functioning of the FMA and provide benefits for future research and educational uses.

The lytic activation of KSHV during keratinocyte differentiation is dependent upon a suprabasal position, the loss of integrin engagement, and calcium, but not the interaction of cadherins.

We previously found that KSHV (HHV-8) lytic activation occurs during differentiation of oral keratinocytes in organotypic raft cultures. To further investigate the spatial and temporal aspects of KSHV lytic activation and the roles of integrins, cadherins, and calcium, we used rKSHV.219-infected primary oral keratinocytes in submerged, suspension, and direct suprabasal plating, models of differentiation. We found that early keratinocyte differentiation did not activate lytic KSHV in cells attached to a substratum, with activation only occurring in suprabasal cells. Temporally, KSHV lytic expression occurred between the expression of early and late differentiation markers. Keratinocytes differentiated in suspension culture, which mimics substratum loss that occurs with stratification, activated lytic KSHV. This lytic activation was inhibited by integrin engagement, showing that integrins are a control point for KSHV reactivation. A role for cadherins was not found. Elevated extracellular calcium was necessary, but not sufficient, for lytic activation.

Content-specific auditing of a large scale anatomy ontology.

Biomedical ontologies are envisioned to be usable in a range of research and clinical applications. The requirements for such uses include formal consistency, adequacy of coverage, and possibly other domain specific constraints. In this report we describe a case study that illustrates how application specific requirements may be used to identify modeling problems as well as data entry errors in ontology building and evolution. We have begun a project to use the UW Foundational Model of Anatomy (FMA) in a clinical application in radiation therapy planning. This application focuses mainly (but not exclusively) on the representation of the lymphatic system in the FMA, in order to predict the spread of tumor cells to regional metastatic sites. This application requires that the downstream relations associated with lymphatic system components must only be to other lymphatic chains or vessels, must be at the appropriate level of granularity, and that every path through the lymphatic system must terminate at one of the two well known trunks of the lymphatic system. It is possible through a programmable query interface to the FMA to write small programs that systematically audit the FMA for compliance with these constraints. We report on the design of some of these programs, and the results we obtained by applying them to the lymphatic system. The algorithms and approach are generalizable to other network organ systems in the FMA such as arteries and veins. In addition to illustrating exact constraint checking methods, this work illustrates how the details of an application may reflect back a requirement to revise the design of the ontology itself.

Angiogenic heterogeneity in head and neck squamous cell carcinoma: biological and therapeutic implications.

The literature contains numerous references describing heterogeneity for tumor phenotypes including cell proliferation, invasiveness, metastatic potential, and response to therapies. However, data regarding angiogenic heterogeneity are limited. In this study, we investigated the degree of intertumoral angiogenic heterogeneity present in head and neck squamous cell carcinomas (HNSCC). In addition, we investigated the biological relevance that this heterogeneity may have in the context of cytokine directed antiangiogenic therapy. Keratinocytes were harvested from HNSCC specimens using laser capture microdissection (LCM). Gene expression profiling of the RNA extracted from these specimens demonstrated variability in the expression of angiogenesis-related genes. Hierarchical clustering and principal component analyses (PCA) demonstrated the presence of unique patient clusters, suggesting that there may be two potentially distinct pathways by which HNSCC induce angiogenesis. Immunohistochemistry for VEGF, IL-8/CXCL8, HGF, and FGF-2, cytokines that play functional roles in HNSCC angiogenesis was performed on the original patient samples as well as a larger panel of normal, dysplastic and HNSCC specimens to validate the heterogeneous expression observed in the gene expression profiling studies. Finally, the therapeutic response of HNSCC tumor xenografts to anti-VEGF therapy was found to be dependent on the amount of VEGF produced by the tumor cells. These findings support the hypothesis of intertumoral angiogenic heterogeneity. They imply that there are differences with regard to the specific molecular mechanisms by which individual tumors within the same histological type induce angiogenesis. Moreover, they demonstrate the need for a more in-depth understanding of the variability of the angiogenic phenotype within a given type of neoplasm when designing cytokine targeted antiangiogenic therapies. Finally, they suggest that studies in conjunction with the ongoing clinical trials that explore the correlation between target expression and clinical outcome are warranted.

Tumor-specific genetic expression profile of metastatic oral squamous cell carcinoma.

BACKGROUND: Metastasis is the most important predictor of survival in patients with oral squamous cell carcinoma (OSCC). We tested the hypothesis that there is a genetic expression profile associated with OSCC metastasis. METHODS: We obtained samples from 6 OSCC node-positive primary tumors and their matched metastatic lymph nodes, and 5 OSCC node-negative primary tumors. Using laser capture microdissection, we isolated OSCC cells from metastatic lymph nodes and compared them with those from matched primary tumors and unmatched node-negative primary tumors using Affymetrix Human Genome Focus arrays. RESULTS: Comparison of tumor cells from the lymph nodes with those from the unmatched, node-negative primary tumors revealed differential expression of 160 genes. Hierarchical clustering and principal component analysis using this 160-gene set showed that the node-negative samples were distinguishable from both, node-positive primary tumors and tumors in the lymph nodes. Many of the expression changes found in the metastatic cells from the lymph nodes were also found in the node-positive primary tumors. Immunohistochemical analysis for transglutaminase-3 and keratin 16 confirmed the differential genetic expression for these genes. CONCLUSION: These preliminary results suggest that there may be a metastatic gene expression profile present in node-positive primary OSCC.