Ameloblastoma: Epidemiology and Development of New Treatment Options

Ameloblastoma is one of the most common epithelial odontogenic benign tumors in the jaws, locally invasive, and has a high recurrence rate if not treated adequately. Several studies published over many years report the incidence of ameloblastoma in many nations. Nevertheless, no study has been conducted on the global incidence of ameloblastoma. Therefore, Chapter 2, we undertook a systematic review and meta-analysis (SRMA) to examine worldwide incidents across five decades and present an updated profile of ameloblastoma patients throughout the previous 26 years. We discovered that the global incidence rate was 0.92 per million person-years. The mandible was the favored location, with a slight male preference. The average age was 34, with the highest incidence occurring in the third decade of life. When compared to Africa and South America, ameloblastoma was more common in older people in Europe and North America. Solid/multicystic ameloblastoma was the most prevalent type, and follicular and plexiform histopathologic patterns predominated. Chapter 3, we conducted a retrospective study to assess the incidence, treatment, and complication profiles of ameloblastoma patients in East Indonesia. The mean age was 39.7 years, and most tumors were located in the posterior part of the mandible. The most common type was multicystic ameloblastoma; most cases were treated conservatively. For patients receiving radical treatment, reconstructions were done without bone grafts and only with titanium plates. We discovered that the most typical pre-operative complication is swelling. Chapter 4, we performed a SRMA s to evaluate the results of radical and conservative treatment methods for solid/multicystic and unicystic ameloblastoma concerning recurrence rates. We discovered that after radical therapy, the pooled recurrence rate of solid/multicystic ameloblastomas was 8%, compared to 41% after conservative treatment. These percentages were 3% and 21% for unicystic ameloblastomas, respectively. Following radical treatment, the risk of recurrences for both types of ameloblastomas was significantly lower than for conservative patients. The solid/multicystic variety revealed more recurrences than the unicystic type, but it is essential to remember that this research only included retrospective observational studies, which makes the evidence weaker than ideal. Chapter 5, for the first time in the ameloblastoma research field, we conducted a network meta-analysis (NMA) to evaluate and compare the efficacy of these various treatment modalities simultaneously for solid/multicystic ameloblastoma. According to the results, segmental resection ranked highest for lowering the recurrence rate, followed by curettage with cryotherapy and marginal resection. However, the evidence's certainty was deemed low for all comparisons by the Confidence in Network Meta-Analysis (CINeMa) technique because of imprecision and within-study bias. Our NMA revealed segmental resection as the most effective surgical method for decreasing recurrence in patients with multicystic ameloblastoma. Combining different conservative approaches is recommended if the patient cannot afford a radical treatment. However, the findings should be interpreted with caution. Knowing the specific tumor receptors targeted by the drug delivery system is one of the necessities for targeted therapy for cancers. Therefore, we carried out surface proteomic analyses in Chapter 6 to look for potential biomarkers that could act as beneficial extracellular targets for the targeted transport and delivery of therapeutic agents to ameloblastoma cells. The ameloblastoma cell line (AM-1)'s biotinylated surface and flow-through fractions were isolated and subjected to gel electrophoresis and nano LC-MS/MS. Protein-protein interactions diagram, gene ontology, and protein clusters were explored to understand the ameloblastoma tumor biology. Based on the screening of multiple variables, 17 proteins were determined to be high-confidence surface proteins. These results were compared to the public normal tissue dataset to assess protein expression in the healthy oral mucosa. Ultimately, we revealed five potential biomarkers with minimal expression in oral mucosa: PTPRF, PLXNA1, PLNA2, DCBLD2, and EPHB4.