To provide a systematic review of the literature on studies comparing the immunoprofile of nevoid basal cell carcinoma syndrome (BCNS)–associated and sporadic odontogenic keratocysts (OKCs), in order to identify markers that could accurately distinguish the two OKC subtypes.
Materials and methods
We searched MEDLINE/Pubmed, Web of Science, EMBASE via OVID, and grey literature for publications until December 28th, 2019, that compared the immunohistochemical expression of the two OKC subtypes. The studies were qualitatively assessed using the Critical Appraisal Tool for Case Series (Joana Briggs Institute). Sensitivity and specificity, positive and negative likelihood ratio, diagnostic odds ratio and area under the curve, and pooled estimates were calculated, using a random-effects model.
Seventy-one studies were qualitatively analyzed; 61 markers were evaluated in one study and 32 in ≥ 2 studies. Twenty-five studies reported differential expression of 29 markers in the form of higher number of positive cells or greater staining intensity usually in BCNS-associated OKCs. Meta-analysis for bcl-2, Cyclin D1, CD56, CK18, p53, and PCNA showed that none of those markers is distinguishable between BCNS-associated and sporadic OKCs, in a 95% confidence interval. The risk of bias was high in 34 studies, moderate in 22, and low in 15.
The present systematic review and meta-analysis uncovered that, although several immunohistochemical markers might characterize the OKC phenotype, they cannot discriminate between the BCNS-associated and sporadic OKCs.
This study highlighted the requirement for additional screening for markers by immunohistochemistry, preferentially coupled to alternative diagnostic applications such as genomics technologies.
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The authors thank Dr. Apostolos Klinakis (Investigator-Professor Level, Center of Basic Research, Biomedical Research Foundation, Academy of Athens, Athens, Greece) and Dr. Theodoros Rampias (Investigator-Assistant Professor Level, Center of Basic Research, Biomedical Research Foundation, Academy of Athens, Athens, Greece) for the critical proofreading of the manuscript and their constructive comments.
This research is co-financed by Greece and the European Union (European Social Fund-ESF) through the Operational Programme «Human Resources Development, Education and Lifelong Learning» in the context of the project “Strengthening Human Resources Research Potential via Doctorate Research” (MIS-5000432), implemented by the State Scholarships Foundation (ΙΚΥ). This funding source supports the author Eleni-Marina Kalogirou and had no involvement in study design, in the collection, analysis, and interpretation of data, in the writing of the report, and in the decision to submit the report for publication.
This article does not contain any studies with human participants or animals performed by any of the authors.
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Kalogirou, EM., Thermos, G., Zogopoulos, V. et al. The immunohistochemical profile of basal cell nevus syndrome–associated and sporadic odontogenic keratocysts: a systematic review and meta-analysis. Clin Oral Invest (2021). https://doi.org/10.1007/s00784-021-03877-w
- Odontogenic keratocyst
- Basal cell nevus syndrome
- Nevoid basal cell carcinoma syndrome
- Systematic review