BRAF p.V600E status in epithelial areas of ameloblastoma with different histological aspects: Implications to the clinical practice.

BACKGROUND: BRAF p.V600E is reported in up to 80% of ameloblastomas. Despite the high frequency, the presence of this mutation in different histopathological areas of the tumour has not been investigated. This information has an important role in the use of BRAF p.V600E assessment as an auxiliary tool in the differential diagnosis between unicystic ameloblastoma and other odontogenic cystic lesions, especially when only incisional biopsies are available. Therefore, the purpose of the present study was to investigate BRAF p.V600E heterogeneity in unicystic ameloblastoma. METHODS: Five cases of ameloblastoma and two dentigerous cysts were analysed. The regions exhibiting different microscopic characteristics were selected from each ameloblastoma case and manually dissected. TaqMan allele-specific qPCR or Sanger sequencing was performed to determine BRAF p.V600E status. RESULTS: We screened the mutation in a small cohort of UA and no molecular heterogeneity was found. Four cases of ameloblastoma (80%) exhibited BRAF p.V600E in all different areas evaluated. One case did not harbour the mutation in any microscopic region analysed. The BRAF mutation was absent in the dentigerous cysts. CONCLUSION: Ameloblastomas appear to exhibit a homogeneous profile regarding the BRAF p.V600E no matter what histological feature is observed under light microscopy, suggesting that this molecular test may contribute to establish the correct diagnosis in cases microscopically resembling other odontogenic lesions.

Molecular basis of oral squamous cell carcinoma in young patients: Is it any different from older patients?

Oral squamous cell carcinoma (OSCC) is the commonest subtype of oral cancer, mainly affecting older patients. It used to be a rare disease among individuals younger than 40 years, but recently increased incidences in this age group are being reported worldwide. The pathogenesis of OSCC affecting young patients remains controversial, and the well-known etiological factors for oral cancer, tobacco, and alcohol use are believed to play a minor role in the carcinogenesis of the neoplasm, suggesting that the etiology and the molecular basis of OSCC may differ between younger and older patients. Although several molecular markers and chromosomal abnormalities have been demonstrated to differ between both groups, most of the studies have failed to find significant differences. Moreover, divergent results have also been obtained regarding the presence of high-risk human papillomavirus infection in OSCC of young patients. Given these contradictory results and the limited methodological approaches of the majority of the studies, the exact difference between both age groups remains to be fully established. In this review, we evaluate the available data to establish the current evidence that might support the hypothesis that the molecular basis of OSCC in young patients (especially those under 40 years) differ from the older patients.

Prognostic importance of the lymphovascular invasion in head and neck adenoid cystic carcinoma: A systematic review and meta-analysis.

The presence of lymphovascular invasion is considered a prognostic determinant for different human neoplasms and is frequently taken into account by surgeons and oncologists to determine patients' treatment. However, the exact frequency of this microscopic event and its prognostic impact for patients affected by adenoid cystic carcinoma (AdCC) remains unclear. Therefore, the aim of this study was to carry out a systematic review and meta-analysis to address the prevalence and the prognostic potential of lymphovascular invasion in head and neck AdCC. A literature search on PubMed, Scopus, ClinicalTrials.gov, Web of Science and ProQuest databases was undertaken in January 2019. The primary outcomes of interest were overall survival (OS) and disease-free survival (DFS). The relative frequency of lymphovascular invasion and its possible association with other clinicopathological parameters were addressed. A total of 22 studies and 2117 patients were included in this study. The frequency of lymphovascular invasion ranged from 5.2% to 72.5%. Lymphovascular invasion was associated with an increased likelihood of lymph node metastasis (OR = 2.58; 95% CI 1.61-4.12; p = 0.0001) and death (OR = 3.09; 95% CI 1.82-5.26; p = 0.0001), solid/higher-grade AdCC were more likely to present lymphovascular invasion (OR = 5.51; 95% CI 1.87-16-21; p = 0.002) and patients with this microscopic finding had a significantly lower OS (HR = 8.30; 95% CI 1.68-40.91; p = 0.009) and DFS (HR = 3.76; 95% CI 1.13-12.53; p = 0.03). In conclusion, lymphovascular invasion seems to be a significant predictor of poor prognosis for head and neck AdCC patients.

Mass spectrometry-based proteome profile may be useful to differentiate adenoid cystic carcinoma from polymorphous adenocarcinoma of salivary glands.

OBJECTIVE: The aim of this study was to determine the proteome of adenoid cystic carcinoma (AdCC) and polymorphous adenocarcinoma (PAc) and to identify a protein signature useful in distinguishing these two neoplasms. STUDY DESIGN: Ten cases of AdCC and 10 cases of PAc were microdissected for enrichment of neoplastic tissue. The samples were submitted to liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the proteomics data were analyzed by using the MaxQuant software. LC-MS/MS spectra were searched against the Human UniProt database, and statistical analyses were performed with Perseus software. Bioinformatic analyses were performed by using discovery-based proteomic data on both tumors. RESULTS: LC-MS/MS analysis identified 1957 proteins. The tumors shared 1590 proteins, and 261 were exclusively identified in AdCC and 106 in PAc. Clustering analysis of the statistically significant proteins clearly separated AdCC from PAc. Protein expression 10 times higher in one group than in the other led to a signature of 16 proteins-6 upregulated in AdCC and 10 in PAc. A new clustering analysis showed reverse regulation and also differentiated both tumors. CONCLUSIONS: Global proteomics may be useful in discriminating these two malignant salivary neoplasms that frequently show clinical and microscopic overlaps, but additional validation studies are still necessary to determine the diagnostic potential of the protein signature obtained.