BRAF in papillary thyroid carcinoma.

Novel genetic findings about papillary thyroid carcinoma identify BRAF gene as a subject of great interest. Involvement of BRAF gene in pathogenesis of PTC, diagnostic value and the putative prognostic significance of its T1799A mutation are summarized in this article. Furthermore, a particular attention is focused to the role of pre-operative detection of BRAF mutation in the FNAB specimens of thyroid nodules and to the use of this gene as target for an effective cancer therapy.

Ultrasound-guided percutaneous laser ablation in treating symptomatic solid benign thyroid nodules: Our experience in 45 patients.

BACKGROUND: Laser ablation may be useful in debulking of benign thyroid nodules. METHODS: In order to retrospectively evaluate the effectiveness and safety of laser ablation, 45 patients with benign solid thyroid nodules, with a fluid component ≤20%, were included in our series between October 2009 and January 2011. All reported pressure and/or cosmetic complaints. Nd:YAG laser at 1064 nm was used, with a fix-power (3W), changing the application time. All patients were evaluated at baseline, 6 months, and 12 months and any complications were recorded. RESULTS: Mean nodule volume reduction decreased from 24.2 mL ± 19.4 to 4.5 ± 5.2 at 12 months (p < .001). Mean nodule volume reduction was 84% ± 13. Cosmetic signs were completely resolved in 87%, reduced in 9%, unchanged in 2%, and pressure symptoms were resolved in 88%. One patient experienced transient dysphonia. CONCLUSION: Ultrasound-guided laser ablation is an effective tool for treatment of symptomatic benign thyroid nodules in patients not eligible for surgery.

Telomeres, telomerase and oral cancer (Review).

Oral squamous cell carcinoma (oral cancer) and many squamous cell carcinomas of the head and neck arise as a consequence of multiple molecular events induced by the effects of various carcinogens related to tobacco use, environmental factors, and viruses in some instances (e.g., mucosal oncogenic human papillomaviruses), against a background of inheritable resistance or susceptibility. Consequent genetic damage affects many chromosomes and genes, and it is the accumulation of these changes that appears to lead to carcinoma. Telomere maintenance by telomerase or, in its absence, alternative lengthening of telomeres protect this acquired altered genetic information ensuring immortality without losing eukaryotic linear DNA; when this does not occur DNA is lost and end-replication problems arise. Telomerase is reactivated in 80-90% of cancers thus attracting the attention of pathologists and clinicians who have explored its use as a target for anticancer therapy and to develop better diagnostic and prognostic markers. In the last few years, valuable research from various laboratories has provided major insights into telomerase and telomeres leading to their use as diagnostic and prognostic markers in several types of cancer. Moreover, many strategies have emerged which inhibit this complex enzyme for anticancer therapy and are one step ahead of clinical trials. This review explains the basic biology and the clinical implications of telomerase-based diagnosis and prognosis, the prospects for its use in anticancer therapy, and the limitations it presents in the context of oral cancer.

The European accreditation of Istituto Tumori Giovanni Paolo II of Bari.

The National Cancer Institute of Bari (Istituto di Ricovero e Cura a Carattere Scientifico, IRCCS) has been involved since the conception of the project of the Italian Ministry for Health aimed to validate the applicability of the Organisation of European Cancer Institutes (OECI) accreditation and designation (A&D) model to the Network of Italian Cancer Centers, IRCCS, of Alleanza Contro il Cancro. The self-assessment phase of the Institute started in September 2013 and ended in June 2014. All documents and tools were transferred to the OECI A&D Board in June 2014 and a 2-day peer review visit was conducted in October 2014 by an international qualified audit team. The Institute received its final designation and certification in June 2015. The OECI A&D Board, in its final report, came to the conclusion that Istituto Tumori "Giovanni Paolo II" of Bari has a strong research component with some essential elements of comprehensive cancer care still under development; the lack of a system for using outcome data for the strategic management approach to decision-making and missing a regular internal audit system eventually helping further quality improvement were reported as examples of areas with opportunities for improvement. The OECI A&D process represented a great opportunity for the cancer center to benchmark the quality of its performance according to standard parameters in comparison with other international centers and to further develop a participatory group identity. The common goal of accreditation was real and participatory with long-lasting positive effects. We agree with the OECI comments about the next areas of work in which the Institute could produce future further efforts: the use of its powerful IT system as a means for outcome analysis and empowerment projects for its cancer patients.

Microvessel density, mast cell density and thymidine phosphorylase expression in oral squamous carcinoma.

To elucidate the role of angiogenesis in the carcinogenesis and progression of oral cancer, we investigated microvessel density (mVd), mast cell density (mCd) and thymidine phosphorylase (TP) expression in a series of 50 patients with T1-3 N0-1 M0 oral squamous carcinoma (OSC) and 21 patients with non-dysplastic oral leukoplakia (NDOLP). Paraffin-embedded pathological tissue was utilised for the immunohistochemical analysis of mVd and TP expression. Toluidine blue histochemical method was employed for mast cell identification. OSC and NDOLP were not significantly different with respect to mVd (mVd mean value +/- SD: 30+/-17 and 27+/-18, respectively) and mCd characteristics (mCd mean value +/- SD: 8+/-6 and 7+/-6 units, respectively). Conversely, tumour epithelia showed some degree of TP immunostaining in 100% of cases compared with 76% in NDOLP samples (p< or =0.001 by Fisher's test). A good correlation was found between mVd and mCd in both NDOLP (c.c. 0.632; p=0.002) and OSC (c.c. 0.496; p=0.000) tissue, whereas no association between TP expression and mVd or between mCd and TP status was evident. At a median follow-up of 18 months, patients with high mVd tumours showed a greater probability of survival than those with low mVd (75 and 40%, respectively; p=0.04 log-rank test). Our results suggest that the development of oral cancer epithelia is associated with a significant increase in TP expression. Conversely, the clinical outcome of OSC seems inversely related specifically to mVd.

Altered p16INK4a and Fhit expression in carcinogenesis and progression of human oral cancer.

To further characterize the biological and clinical role of molecular alterations involved in oral squamous carcinogenesis, the immunohistochemical expression level of two tumor suppressor genes, fragile histidine triad and p16INK4a, in non-carcinomatous squamous epithelia and head and neck squamous cell carcinoma was determined. In addition, human papillomavirus infection determined by PCR assay and the use of alcohol and cigarettes were evaluated. In this study 28 non-carcinomatous squamous epithelia and 57 head and neck squamous cell carcinoma were considered. The expression levels of fragile histidine triad were lower in head and neck squamous cell carcinoma than in non-carcinomatous squamous epithelia. In contrast, p16INK4a is expressed in malignant lesions (51% of the cases analyzed), but not in non-carcinomatous squamous epithelia. No correlation between gene expression alterations of the two tumor suppressors was observed. PCR analysis showed that HPV DNA was present in 5 of the 57 malignant lesions analyzed (8.8%). None of the factors described above, despite changes in gene expression and HPV infection, appears to be associated with alcohol use and/or tobacco smoking and clinical outcome. Our data showed that fragile histidine triad and p16INK4a expression are altered in malignant lesions. Most likely, the decreasing levels of fragile histidine triad is directly involved in cancer development, while the accumulation of p16INK4a in head and neck squamous cell carcinoma may be the consequence of loss of functional tumor suppressor retinoblastoma pathway.

Fluorescence in situ hybridization analysis of HER-2/neu in brushings of normal oral mucosa.

Oncogene alterations have been clearly demonstrated to be related to the carcinogenesis and progression of oral squamous cell carcinoma (OSCC). However, the analysis of these alterations for screening and early diagnostic purposes generally requires invasive techniques for surgical removal of pathological epithelium. The aim of the present study was to assess the feasibility of fluorescence in situ hybridization (FISH) analysis of HER-2/neu amplification in oral mucosa brushings and to compare the HER-2/neu status with the history and smoking and drinking habits of healthy subjects. Cells obtained by centrifugation of oral brushings from 21 subjects (overall no. of cells: 5125) were suspended in physiological saline and fixed onto two slides for cytological evaluation and FISH analysis (dual-target, dual-color fluorescence assay) of the HER-2/neu gene and CEP17 centromere. A mean of 89.8% of the cells showed two HER-2/neu signals and a mean of 94% had two CEP17 signals at fluorescent microscopy. Finally, a mean of 96% of cells with HER-2/neu / CEP17 had a ratio equal to 1. No association between smoking and drinking habits, age and the HER-2/neu and CEP17 characteristics evaluated by FISH was found.