Browsing by Author "Saba, Nabil F."
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- Chromosome translocations, gene fusions, and their molecular consequences in pleomorphic salivary gland adenomasPublication . Stenman, Göran; Fehr, Andre; Skálová, Alena; Vander Poorten, Vincent; Hellquist, Henrik; Mikkelsen, Lauge Hjorth; Saba, Nabil F.; Guntinas-Lichius, Orlando; Chiesa-Estomba, Carlos Miguel; Andersson, Mattias K.; Ferlito, AlfioSalivary gland tumors are a heterogeneous group of tumors originating from the major and minor salivary glands. The pleomorphic adenoma (PA), which is the most common subtype, is a benign lesion showing a remarkable morphologic diversity and that, upon recurrence or malignant transformation, can cause significant clinical problems. Cytogenetic studies of >500 PAs have revealed a complex and recurrent pattern of chromosome rearrangements. In this review, we discuss the specificity and frequency of these rearrangements and their molecular/clinical consequences. The genomic hallmark of PA is translocations with breakpoints in 8q12 and 12q13-15 resulting in gene fusions involving the transcription factor genes PLAG1 and HMGA2. Until recently, the association between these two oncogenic drivers was obscure. Studies of the Silver-Russel syndrome, a growth retardation condition infrequently caused by mutations in IGF2/HMGA2/PLAG1, have provided new clues to the understanding of the molecular pathogenesis of PA. These studies have demonstrated that HMGA2 is an upstream regulator of PLAG1 and that HMGA2 regulates the expression of IGF2 via PLAG1. This provides a novel explanation for the 8q12/12q13-15 aberrations in PA and identifies IGF2 as a major oncogenic driver and therapeutic target in PA. These studies have important diagnostic and therapeutic implications for patients with PA.
- Neutrophil to lymphocyte ratio in oropharyngeal squamous cell Carcinoma: A systematic review and meta-analysisPublication . Rodrigo, Juan P.; Sánchez-Canteli, Mario; Triantafyllou, Asterios; de Bree, Remco; Mäkitie, Antti A.; Franchi, Alessandro; Hellquist, Henrik; Saba, Nabil F.; Stenman, Göran; Takes, Robert P.; Valero, Cristina; Zidar, Nina; Ferlito, AlfioNeutrophil-to-lymphocyte ratio (NLR) has been associated with survival in various cancers, including head and neck cancer. However, there is limited information on its role in oropharyngeal squamous cell carcinomas (OPSCC) according to HPV status. This prompted the present metaanalysis. Studies were selected when the prognostic value of NLR prior to treatment was evaluated in OPSCC patients, the cutoff value of NLR was available, and the prognostic value of NLR was evaluated by time-to-event survival analysis. A total of 14 out of 492 articles, including 7647 patients, were analyzed. The results showed a worse prognosis for the patients with a high NLR: The combined hazard ratios (HR) for overall survival (OS) in patients with an elevated NLR was 1.56 (95% confidence interval (CI) 1.21–2.02; p = 0.0006), for disease-free survival was 1.52 (95% CI 1.34–1.73; p < 0.00001), and for recurrence-free survival was 1.86 (95% CI 1.50–2.30; p < 0.00001). This worse prognosis ofhigh NLR was exclusive of HPV-positive patients: HR for OS in the HPV-positive subgroup was 4.05 (95% CI 1.90–8.62 (p = 0.0003), and in the HPV-negative subgroup 0.92 (95% CI 0.47–1.80; p = 0.82). The prognosis of NLR was not influenced by treatment: The HR for OS for patients treated with radiotherapy/chemoradiotherapy (RT/CRT) was 1.48 (95% CI 1.09–2.01; p = 0.01), and for patients treated with surgery (±RT/CRT) was 1.72 (95% CI 1.08–2.72; p = 0.02). In conclusion, an elevated NLR relates to worse outcomes in patients with HPV-positive OPSCC.
- Update on olfactory neuroblastomaPublication . Lopez, Fernando; Agaimy, Abbas; Franchi, Alessandro; Suárez, Carlos; Vander Poorten, Vincent; Mäkitie, Antti A.; Homma, Akihiro; Eisbruch, Avraham; Olsen, Kerry D.; Saba, Nabil F.; Nuyts, Sandra; Snyderman, Carl; Beitler, Jonathan J.; Corry, June; Hanna, Ehab; Hellquist, Henrik; Rinaldo, Alessandra; Ferlito, AlfioOlfactory neuroblastomas are uncommon malignancies that arise from olfactory receptor cells located high in the nasal cavity. Accurate diagnosis plays a crucial role in determining clinical results and guiding treatment decisions. Diagnosis can be a major challenge for pathologists, especially when dealing with tumours with poor differentiation. The discovery of several molecular and immunohistochemical markers would help to overcome classification difficulties. Due to the paucity of large-scale studies, standardisation of diagnosis, treatment and prediction of outcome remains a challenge. Surgical resection by endoscopic techniques with the addition of postoperative irradiation is the treatment of choice. In addition, it is advisable to consider elective neck irradiation to minimise the risk of nodal recurrence. Molecular characterisation will help not only to make more accurate diagnoses but also to identify specific molecular targets that can be used to develop personalised treatment options tailored to each patient. The present review aims to summarise the current state of knowledge on histopathological diagnosis, the molecular biology and management of this disease.