Immunohistochemical Analysis of Dentigerous Cysts and Odontogenic Keratocysts Associated with Impacted Third Molars-A Systematic Review

Objective: This systematic review investigates the diagnostic, prognostic, and therapeutic implications of immunohistochemical markers in dentigerous cysts (DCs) and odontogenic keratocysts (OKCs) associated with impacted third molars. Materials and Methods: A comprehensive search strategy was employed across major databases including MEDLINE/PubMed, EMBASE, and Web of Science, from the inception of the databases to March 2024. Keywords and Medical Subject Heading (MeSH) terms such as "dentigerous cysts", "odontogenic keratocysts", "immunohistochemistry", "Ki-67", and "p53" were used. The PRISMA 2020 guidelines were followed to ensure methodological rigor. Inclusion criteria encompassed studies on humans and animals providing definitive diagnoses or specific signs and symptoms related to DCs and OKCs, with results on protein expression derived from immunohistochemistry, immune antibody, proteomics, or protein expression methods. Results: Of the 159 studies initially identified, 138 met the inclusion criteria. Our analysis highlighted significantly higher expressions of Ki-67 (22.1% +/- 4.7 vs. 10.5% +/- 3.2, p < 0.001), p53 (15.3% +/- 3.6 vs. 5.2% +/- 1.9, p < 0.001), and Bcl-2 (18.4% +/- 3.2 vs. 8.7% +/- 2.4, p < 0.001) in OKCs compared to DCs, indicating a higher proliferative index, increased cellular stress, and enhanced anti-apoptotic mechanisms in OKCs. Additionally, PCNA levels were higher in OKCs (25.6% +/- 4.5 vs. 12.3% +/- 3.1, p < 0.001). Genetic mutations, particularly in the PTCH1 gene, were frequently observed in OKCs, underscoring their aggressive behavior and potential malignancy. Conclusions: The findings emphasize the significant role of immunohistochemical markers in distinguishing between DCs and OKCs, with elevated levels of Ki-67, p53, Bcl-2, and PCNA in OKCs suggesting a higher potential for growth and recurrence. Genetic insights, including PTCH1 mutations, further support the need for personalized treatment approaches. These markers enhance diagnostic accuracy and inform targeted therapeutic strategies, potentially transforming patient management in oral and maxillofacial surgery.