Effects of tobacco abuse on major chromosomal instability in human papilloma virus 16-positive oropharyngeal squamous cell carcinoma.

A substantial number of patients with oropharyngeal squamous cell carcinoma (OPSCC) have two oncogenic risk factors: Human papilloma virus (HPV) infection and tobacco use. These factors can be competitive or synergistic at the chromosomal and genomic levels, with strong prognostic and therapeutic implications. HPV16 has been shown in vitro to be a high­risk HPV that induces low rates of chromosomal copy number alterations. However, chromosomal instability can be increased by smoking. Evaluating chromosomal instability in HPV­positive patients according to their smoking status is therefore critical for assessing the prognosis and therapeutic impact. The aim of this study was to assess chromosomal instability in patients with HPV­positive OPSCC according to smoking status. Chromosomal instability was investigated with array­based comparative genomic hybridization (aCGH) in 50 patients with OPSCC. Differences in chromosomal alterations were examined according to the HPV and smoking status of the patients. HPV­positive tumors (24/26 were HPV16­positive) had fewer genomic aberrations (P=0.0082) and fewer breakpoints (P=0.048) than HPV­negative tumors. We confirmed the association between HPV­positive OPSCC and chromosomal losses at 11q. We verified the association between HPV­negative OPSCC and losses at 3p and 9p and gains at 7q and 11q13. In the patients with OPSCC who were HPV­positive, the total number of chromosomal aberrations per tumor was significantly higher in the group of patients who were smokers (P=0.003). However, the cytobands did not differ significantly according to the smoking status. On the whole, the data of this study may help to improve the stratification of HPV­positive OPSCC patients and must be supplemented by next­generation sequencing studies in order to describe the mutational and transcriptomic profiles of such patients according to smoking status.

BRAF V600E detection in cytological thyroid samples: A key component of the decision tree for surgical treatment of papillary thyroid carcinoma.

BACKGROUND: Whether preoperative knowledge of the BRAF mutation status would help to determine the extent of surgery for thyroid nodules is still under investigation. METHODS: We developed a method to state the V600E mutation before surgery on fine-needle aspiration (FNA) stained smears checked to contain tumor cells. We evaluated the interest of the preoperative assessment of the mutation for surgical strategy of nodules, diagnosed as malignant, suspicious for malignancy or follicular neoplasms. RESULTS: The mutation was found in 81% (79 of 97) malignant, 59% (20 of 34) suspicious nodules, and in none of follicular neoplasms (n = 29). Overall, the mutation was detected in 82% of papillary carcinomas. The sensitivity, specificity, and positive and negative predictive values for the diagnosis of malignancy were 75%, 100%, 100%, and 46%, respectively. CONCLUSION: The preoperative knowledge of the V600E mutation status is fundamental to plan total thyroidectomy with certainty and should be part of the decision tree for the management of thyroid nodules. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1017-1021, 2016.

Detection of specific chromosomal aberrations in urine using BCA-1 (oligo-CGH-array) enhances diagnostic sensitivity and predicts the aggressiveness of non-muscle-invasive bladder transitional cell carcinoma.

INTRODUCTION: Bladder carcinoma (B-TCC) is the fifth most prevalent carcinoma in the United States (US) or Europe. In addition, B-TCC is the most expensive carcinoma per patient between diagnosis and death, because of its 50-80 % recurrence rate. B-TCC is an optimal carcinoma for which to detect DNA alterations in urine, which is easily obtainable. Chromosomal aberrations in tumors have been closely related to the carcinogenesis process. MATERIAL AND METHODS: We developed a highly specific and sensitive oligo-CGH-array for the diagnosis and follow-up of B-TCC, based on the detection of chromosomal aberrations in urine samples. One hundred and sixty-four urine samples were analyzed. The qualitative results, including chromosomal aberrations, were obtained. Quantitative results are expressed as a percentage of chromosomal alterations on the autosomes. RESULTS: From the urine samples, we were able to differentiate B-TCC from non-malignant conditions with an accuracy of 100 % for patients without history of B-TCC. For follow-up of B-TCC in clinical practice, at least a deletion (8p; 9p; 9q) or a cut-off of >2 % of chromosomal imbalance was considered as a positive test. According to our criteria, 100 % of high-grade tumors were diagnosed, and the sensitivity to predict positive cystoscopy was 95 % (specificity 73 %). A cut-off >9 % was a strong signature of high-grade TCC (odds ratio 53 CI 95 % 7-417; p = 0.0002). CONCLUSION: We developed a sensitive clinical tool for the detection of B-TCC using DNA extracted from patient urine. This tool is also able to identify low-grade B-TCC and identify high-risk patients harboring a high-grade disease.