In-depth characterization of the salivary adenoid cystic carcinoma transcriptome with emphasis on dominant cell type.

BACKGROUND: Adenoid cystic carcinoma (ACC), 1 of the most common salivary gland malignancies, arises from the intercalated ducts, which are composed of inner ductal epithelial cells and outer myoepithelial cells. The objective of this study was to determine the genomic subtypes of ACC with emphasis on dominant cell type to identify potential specific biomarkers for each subtype and to improve the understanding of this disease. METHODS: A whole-genome expression study was performed based on 42 primary salivary ACCs and 5 normal salivary glands. RNA from these specimens was subjected to expression profiling with RNA sequencing, and results were analyzed to identify transcripts in epithelial-dominant ACC (E-ACC), myoepithelial-dominant ACC (M-ACC), and all ACC that were expressed differentially compared with the transcripts in normal salivary tissue. RESULTS: In total, the authors identified 430 differentially expressed transcripts that were unique to E-ACC, 392 that were unique to M-ACC, and 424 that were common to both M-ACC and E-ACC. The sets of E-ACC-specific and M-ACC-specific transcripts were sufficiently large to define and differentiate E-ACC from M-ACC. Ingenuity pathway analysis identified known cancer-related genes for 60% of the E-ACC transcripts, 69% of the M-ACC transcripts, and 68% of the transcripts that were common in both E-ACC and M-ACC. Three sets of highly expressed candidate genes-distal-less homeobox 6 (DLX6) for E-ACC; protein keratin 16 (KRT16), SRY box 11 (SOX11), and v-myb avian myeloblastosis viral oncogene homolog (MYB) for M-ACC; and engrailed 1 (EN1) and statherin (STATH), which are common to both E-ACC and M-ACC)-were further validated at the protein level. CONCLUSIONS: The current results enabled the authors to identify novel potential therapeutic targets and biomarkers in E-ACC and M-ACC individually, with the implication that EN1, DLX6, and OTX1 (orthodenticle homeobox 1) are potential drivers of these cancers. Cancer 2016;122:1513-22. © 2016 American Cancer Society.

Identification of a gene signature for rapid screening of oral squamous cell carcinoma.

PURPOSE: Oral cancer is a major health problem worldwide and in the U.S. The 5-year survival rate for oral cancer has not improved significantly over the past 20 years and remains at approximately 50%. Patients diagnosed at an early stage of the disease typically have an 80% chance for cure and functional outcome, however, most patients are identified when the cancer is advanced. Thus, a convenient and an accurate way to detect oral cancer early will decrease patient morbidity and mortality. The ability to noninvasively monitor oral cancer onset, progression, and treatment outcomes requires two prerequisites: identification of specific biomarkers for oral cancers as well as noninvasive access to and monitoring of these biomarkers that could be conducted at the point of care (i.e., practitioner's or dentist's office) by minimally trained personnel. EXPERIMENTAL DESIGN: Here, we show that DNA microarray gene expression profiling of matched tumor and normal specimens can identify distinct anatomic site expression patterns and a highly significant gene signature distinguishing normal from oral squamous cell carcinoma (OSCC) tissue. RESULTS: Using a supervised learning algorithm, we generated a 25-gene signature for OSCC that can classify normal and OSCC specimens. This 25-gene molecular predictor was 96% accurate on cross-validation, averaging 87% accuracy using three independent validation test sets and failing to predict non-oral tumors. CONCLUSION: Identification and validation of this tissue-specific 25-gene molecular predictor in this report is our first step towards developing a new, noninvasive, microfluidic-based diagnostic technology for mass screening, diagnosis, and treatment of pre-OSCC and OSCC.

Laryngeal cancer in the United States: changes in demographics, patterns of care, and survival.

BACKGROUND: Survival has decreased among patients with laryngeal cancer during the past 2 decades in the United States. During this same period, there has been an increase in the nonsurgical treatment of laryngeal cancer. OBJECTIVE: The objectives of this study were to identify trends in the demographics, management, and outcome of laryngeal cancer in the United States and to analyze factors contributing to the decreased survival. STUDY DESIGN: The authors conducted a retrospective, longitudinal study of laryngeal cancer cases. METHODS: Review of the National Cancer Data Base (NCDB) revealed 158,426 cases of laryngeal squamous cell carcinoma (excluding verrucous carcinoma) diagnosed between the years 1985 and 2001. Analysis of these case records addressed demographics, management, and survival for cases grouped according to stage, site, and specific TNM classifications. RESULTS: This review of data from the NCDB analysis confirms the previously identified trend toward decreasing survival among patients with laryngeal cancer from the mid-1980s to mid-1990s. Patterns of initial management across this same period indicated an increase in the use of chemoradiation with a decrease in the use of surgery despite an increase in the use of endoscopic resection. The most notable decline in the 5-year relative survival between the 1985 to 1990 period and the 1994 to 1996 period occurred among advanced-stage glottic cancer, early-stage supraglottic cancers, and supraglottic cancers classified as T3N0M0. Initial treatment of T3N0M0 laryngeal cancer (all sites) in the 1994 to 1996 period resulted in poor 5-year relative survival for those receiving either chemoradiation (59.2%) or irradiation alone (42.7%) when compared with that of patients after surgery with irradiation (65.2%) and surgery alone (63.3%). In contrast, identical 5-year relative survival (65.6%) rates were observed during this same period for the subset of T3N0M0 glottic cancers initially treated with either chemoradiation or surgery with irradiation. CONCLUSIONS: The decreased survival recorded for patients with laryngeal cancer in the mid-1990s may be related to changes in patterns of management. Future studies are warranted to further evaluate these associations.