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Updated: Jul 8, 2025

A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
Published on: March 8, 2022
The role of R21 expression in differential diagnosis of melanocytic lesions
Didem Turcan1, Özgül Paşaoğlu2, Deniz Arik2
1Department of Pathology, Gaziantep Nizip State Hospital, Gaziantep, Turkey.
Background:
Cyclic adenosine monophosphate (cAMP) is an intracellular signal transmitter involved in the regulation of melanocyte growth, proliferation, and melanogenesis. R21 is a monoclonal antibody against the soluble adenylyl cyclase (sAC) protein. Various nuclear and cytoplasmic R21 expression patterns in melanocytic lesions have been previously reported. Pan-nuclear staining was defined as specific for melanoma and was found supportive in the assessment of surgical margins.
Aims:
The aim of this study is to evaluate the different expression patterns of R21 immunostain and investigate its effectiveness in the differential diagnosis of cutaneous malignant and benign melanocytic lesions.
Settings And Design:
Fifty invasive cutaneous melanoma and 50 benign melanocytic proliferation were included in the study.
Materials And Methods:
Paraffin blocks that best reflected tumor morphology were studied via immunohistochemical staining for R21. For all patterns, the cases showing staining in 25% or more tumor cells were considered as positive.
Statistical Analysis Used:
Yates' Chi-square, Pearson Chi-square exact test, Spearman correlation were used.
Results And Conclusions:
Dot-like Golgi staining was characteristic for nevi (12/50) and seen only in one melanoma. Pan-nuclear staining was striking for melanoma (36/50). This pattern was observed in 2 dysplastic and 3 common melanocytic nevi too. None of the Spitz nevi expressed R21 in pan-nuclear pattern. For the diagnosis of melanoma, sensitivity and specificity of the pan-nuclear expression were 72% and 90%, respectively. Positive and negative predictive values were found as 87% and 76%. R21, a second-generation immunohistochemical marker, can be used in the differential diagnosis of benign and malignant melanocytic lesions.
Insights
The R21 antibody shows distinct expression patterns in melanocytic lesions. Pan-nuclear R21 staining is a sensitive and specific marker for melanoma, aiding in differential diagnosis.
Area of Science:
- Immunohistochemistry
- Dermatopathology
- Oncology
Background:
- Cyclic adenosine monophosphate (cAMP) regulates melanocyte functions.
- R21 is a monoclonal antibody targeting soluble adenylyl cyclase (sAC).
- Previous studies noted varied R21 expression in melanocytic lesions, with pan-nuclear staining suggesting melanoma.
Purpose of the Study:
- To analyze R21 immunostain patterns in melanocytic lesions.
- To determine R21's efficacy in differentiating benign from malignant melanocytic lesions.
Main Methods:
- Immunohistochemical staining for R21 on 50 melanomas and 50 benign melanocytic proliferations.
- Analysis of nuclear and cytoplasmic R21 expression patterns.
- Statistical analysis including Chi-square and Spearman correlation.
Main Results:
- Pan-nuclear R21 staining was characteristic of melanoma (72% sensitivity, 90% specificity).
- Dot-like Golgi staining was prevalent in nevi.
- R21 expression patterns showed significant differences between benign and malignant lesions.
Conclusions:
- R21 immunostaining is a valuable tool for the differential diagnosis of cutaneous melanocytic lesions.
- Pan-nuclear R21 expression is a strong indicator of melanoma.
- R21 serves as a reliable second-generation immunohistochemical marker in dermatopathology.
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