Lana L. Jackson

Human papillomavirus-active head and neck cancer and ethnic health disparities

Mortality for black males with head and neck squamous cell carcinoma (HNSCC) is twice that of white males or females. Human papillomavirus (HPV)‐active HNSCC, defined by the concurrent presence of high‐risk type HPV DNA and host cell p16INK4a expression, is associated with decreased mortality. We hypothesized that prevalence of this HPV‐active disease class would be lower in black HNSCC patients compared to white patients.

Use of the Harmonic Scalpel in Superficial and Total Parotidectomy for Benign and Malignant Disease

Objectives: Use of the harmonic scalpel in superficial parotidectomy for benign parotid disease has been shown to reduce surgical time as well as intraoperative blood loss. We sought to determine whether similar results could be achieved with the expanded use of the harmonic scalpel in parotidectomy for both benign and malignant disease.

2D-DIGE proteomic characterization of head and neck squamous cell carcinoma

Objective: Identify proteins that are differentially expressed between head and neck squamous cell cancer (HNSCC) and patient-matched normal adjacent tissue, and validate findings in a separate patient cohort. Study Design: Cross-sectional study of surgical specimens. Setting: Tertiary care academic medical center. Subjects and Methods: Laser capture microdissection and two-dimensional difference gel electrophoresis were used previously to establish proteomic profiles for tumor and normal adjacent tissue from 14 patients. Here, significance analysis of microarray was used to rank candidate biomarkers. Spots meeting statistical and biological criteria of significance were analyzed by liquid chromatography and tandem mass spectrometry to obtain protein identifications. The expression pattern of the highest-ranked candidate biomarker (cornulin) was validated in a larger, independent patient cohort (n = 68) by immunohistochemical staining of a tissue microarray. Results: Of 732 spots, 117 (15.9%) met criteria for significance. Identities were obtained for 39 spots, representing 17 different proteins. Four proteins were novel in the context of HNSCC: glutathione synthetase, which was upregulated; and cornulin (squamous epithelial heat shock protein 53), guanylate binding protein 6, and heat shock 70 kDa protein 5 (glucose-regulated protein, 78 kDa), which were downregulated. Cornulin functions in the stress response in normal squamous epithelium, and reduced expression has been proposed as a marker of susceptibility to laryngopharyngeal reflux and other stressors. Loss of cornulin expression was confirmed in an independent HNSCC patient cohort (P < 0.001). Conclusions: Downregulation of cornulin is a prominent feature of the molecular signature of HNSCC identified by comparative proteomics. Cornulin may represent a link between HNSCC and other pathologies arising in stratified squamous epithelium.

Quantitative Analysis of Syndecan‐1 Expression in Dysplasia and Squamous Cell Carcinoma of the Oral Cavity

Introduction: Decreased expression of syndecan‐1 has been reported in dysplasia and squamous cell carcinoma (SCCA) of the oral cavity and appears to correlate with decreasing histological differentiation and poor clinical outcome. Assays of syndecan‐1 expression to date have utilized manual microscopic analysis with qualitative grading of immunohistochemical staining intensity, which may introduce observer bias. We evaluated syndecan‐1 expression in dysplasia and squamous cell carcinoma (SCCA) of the oral cavity, using a novel automated cellular imaging system that incorporates both staining intensity as well as the percentage of positively stained cells to yield a quantitative value for syndecan‐1 expression.

Prognostic implications of survivin expression in squamous cell carcinoma of the larynx.

Figure 1: Relationship of Serum Survivin Presence and Tumor Stage. Significant correlation of Tumor stage and Presence of Survivin in Serum (0.048) Inhibitors of Apoptosis have been theorized to be potential future targets for cancer treatment due to the role of radiationinduced apoptosis in cancer cell death during treatment1. One particular member of this family of interest in cancer therapy and prognosis is Survivin. Survivin is a small molecular protein involved in both the apoptosis and mitosis cellular pathways. This protein is expressed during embryonic and fetal development, but is normally undetectable in adult tissues2. Recent studies have shown Survivin to be over expressed in lung, gastric, colorectal, and breast cancer. The level of expression of Survivin in many of these cancers has been associated with decreased survival, increased metastasis, and increased risk of recurrence3,4. Survivin has also been shown to be a promising target for future chemotherapy3.

Significance of HSPB1 expression in Head and Neck Squamous Cell Carcinoma: A Meta‐Analysis of published literatures

OBJECTIVE HSPB1 functions to prevent stress-induced cellular damage and has is elevated in multiple cancer types. The significance of HSPB1 in HNSCC remains controversial. We sought to perform a meta-analysis of HSPB1 expression to clarify previous findings. STUDY DESIGN Meta-analysis of all published studies of HSPB1 in HNSCC patients using IHC techniques. METHODS A literature review was performed on PubMed and Google Scholar search engines using terms HSP27, HSPB1, Heat Shock Proteins, Cancer, Head and Neck Squamous Cell Carcinoma. Additional studies were added by review of manuscript bibliographies. Means and standard deviations for continuous data were obtained for overall HSPB1 expression (in cancer, normal and dysplasia), nodal status and TNM stage. Chi-square and Cochrans Q test were used to test statistical significance. RESULTS There were 77 studies identified in the context of HSPB1 and cancer in general. Of these, 7 studies (total patients n=347) met inclusion criteria and reported findings in HNSCC using IHC scoring techniques. For the mean difference in HSPB1 expression; cancer vs. normal, cancer vs. dysplasia, and dysplasia vs. normal all showed significance (p<0.0001) however the difference was not homogeneous across studies for cancer vs. dysplasia and normal. The difference was homogeneous for dysplasia vs. normal. There was no significant difference for HSPB1 expression by nodal status or stage. CONCLUSION HSPB1 is elevated in HNSCC and may be a useful biomarker for this disease.

Multi-spectral imaging analysis of HSPB1 expression in Head and Neck Squamous Cell Carcinoma

The objective of this study was to obtain more accurate quantitation of HSPB1 expression in HNSCC using a novel quantitative protein expression analysis system based on multispectral imaging. The study was a retrospective laboratory study of HNSCC patients treated at tertiary care academic medical center. Archival tissue samples from forty seven patients with HNSCC were subjected to immunohistochemistry using primary antibody to HSPB1. Seven of the patients had early stage cancers (TNM stage I/II) and forty patients had advanced stage cancers (TNM stage III/IV). HSPB1 expression was increased in advanced stage versus early stage cancers. Further investigation of HSPB1 as a potential biomarker for HNSCC is warranted.

Case report of periocular Merkel cell carcinoma treated with primary concomitant chemotherapy and radiation, and review of the literature regarding its use.

Introduction: Merkel Cell Carcinoma (MCC) is a rare, aggressive cutaneous malignancy of neuroendocrine origin. Initially described by Toker1 in 1972, it is thought to arise from cutaneous mechanoreceptors. Nearly half of MCCs occur in the head and neck, making it the most common site of occurrence.2 Due to its rare nature, prospective randomized controlled trials comparing treatment options are lacking.

Minimal Access Neck Dissection

Since the description of the systematic en bloc neck dissection by Crile in 1906, neck dissections have evolved to include functional and minimally invasive techniques. Evidence-based medicine has allowed for the adoption of the selective neck dissection in a number of circumstances. Furthermore, as the primary disease becomes better understood and life expectancies increase, cosmetic outcomes have become an increasing concern in patient care. While this remains secondary to oncologic outcomes, reducing the morbidity of neck dissections has become of great interest. When the primary operative purpose is as a staging procedure, the minimally invasive approach is particularly desirable.

The Natural Progression of an Early Stage Tonsil Carcinoma Treated Initially with Alternative Therapy

Rectus Abdominis free flap was used for reconstruction. Patient M.G. was a 47 year old previously healthy, athletic male who presented to our Multidisciplinary Tumor Board and was diagnosed with a T1N2AM0 squamous cell carcinoma of the right tonsil. It was the consensus of the Tumor Board that he would best be treated with Radiation and Chemotherapy, followed by the possibility of a post-treatment neck dissection should his cervical lymphadenopathy not resolve. His biopsy at the time of diagnosis revealed high risk HPV status.