Carol G. Shores, MD, PhD

Carol G. Shores, MD, PhD, is involved in several research projects. Mihir Patel, MD, PGY2, and Paul Bryson, MD, PGY3, are working to distinguish follicular thyroid carcinomas from adenomas using fine needle aspirations (FNA). This distinction is currently only made after thyroid lobectomy. By examining published expression arrays, we have developed a list of genes whose expression distinguishes follicular thyroid carcinomas from adenomas. We have developed tissue microarrays (TMA) containing hundreds of thyroid specimens with a wide variety of pathologies with funding from the American Head and Neck Society and the UNC Medical Alumni Endowment Fund. Using commercially available antibodies, the TMAs are stained for the proteins encoded by these genes, and multivariant analysis will be used to determine a staining pattern specific for follicular carcinoma versus adenomas. We will then use this staining protocol on FNAs from patients with thyroid nodules to determine if it can be used clinically.

Human papilloma virus is causative in cervical squamous cell carcinoma (SCCA), and is found in 50% of oropharyngeal SCCA. Although it is implied that HPV can transmit oropharyngeal SCCA, this has not been proven. UNC Head and Neck Surgery Division has identified two non-smoking couples with oropharyngeal SCCA. All four patients had low risk factors for developing head and neck cancer. Working with Elizabeth Andrews, DSS (Oral and Maxillofacial Pathology Graduate Student) and Jennifer Webster-Cyriaque, DDS, PhD (School of Dentistry), clinical specimens from these patients have been collected and shown to all contain HPV. The subtype is being determined, and if they match between couples, it will be strong evidence that HPV transmitted the cancer between partners.

Working with Xiaoying Yin, MD, and Neil Hayes, MD (Division of Medical Oncology), we have collected hundreds of HNSCCA tumors from our patients at UNC. Using this tissue bank, we are generating micoarray expression data to compare gene expression in tumors that do and do not respond to combined chemoradiation. In addition, Dr. Hayes and Steve Lee, MD, PGY4, have compared our expression profile with two other HNSCC data sets. This demonstrated two distinct sets of patients defined by their gene expression, with different overall outcomes.

Xiaoying Yin, MD, has been collaborating with Conforma Corporation in examining a novel class of chemotherapy agents, Hsp90 inhibitors. Hsp90 stabilizes cellular proteins, and inhibition can lead to the degradation of several tumor related proteins, thereby interrupting several pathways simultaneously. One inhibitor has been shown to radiosensitize HNSCC in a xenograft model, with minimal side effects and disruption of the expected proteins.

Epstein Barr Virus (EBV) is associated with several different cancers, including Burkett’s Lymphoma. This tumor is rare in North America, but is a common childhood cancer in subsaharan Africa. In tissue culture and animal models, EBV shifts from a drug resistant latent infection to a drug sensitive lytic infection when exposed to chemotherapy. If this is true in human EBV associated cancers, the addition of antiviral therapies with the first round of chemotherapy may increase cure rates. Dr. Shores is the principle investigator of a clinical trial in Malawi Africa to examine changes in EBV virus status in children with Burkett’s Lymphoma. Dr. Paula Harmon, PGY2, has received an American Academy of Otolaryngology/Head and Neck Surgery Foundation Resident Research Award to open this trial. Drs. Shores and Harmon will travel to Malawi in August 2007 to start collecting tissue from Burkett’s patients.