Expression of soluble adenylyl cyclase in lentigo maligna: use of immunohistochemistry with anti-soluble adenylyl cyclase antibody (R21) in diagnosis of lentigo maligna and assessment of margins.

TitleExpression of soluble adenylyl cyclase in lentigo maligna: use of immunohistochemistry with anti-soluble adenylyl cyclase antibody (R21) in diagnosis of lentigo maligna and assessment of margins.
Publication TypeJournal Article
Year of Publication2012
AuthorsMagro CM, Yang S-E, Zippin JH, Zembowicz A
JournalArch Pathol Lab Med
Volume136
Issue12
Pagination1558-64
Date Published2012 Dec
ISSN1543-2165
KeywordsAdenylyl Cyclases, Antibodies, Monoclonal, Antibody Specificity, Biomarkers, Tumor, Cell Nucleus, Diagnosis, Differential, Gene Expression Regulation, Neoplastic, Humans, Hutchinson's Melanotic Freckle, Hyperplasia, Immunohistochemistry, MART-1 Antigen, Melanocytes, Melanoma, Neoplasm Proteins, Nevus, Sensitivity and Specificity, Skin, Skin Neoplasms, Solubility
Abstract

CONTEXT: Soluble adenylyl cyclase (sAC) is an enzyme that generates cyclic adenosine monophosphate, a signaling molecule involved in regulating melanocyte functions. R21, a mouse monoclonal antibody against sAC, shows a striking pan-nuclear staining in lentigo maligna, indicating possible utility for diagnosis and margin assessment.

OBJECTIVE: To evaluate R21 in the diagnosis and evaluation of margins in lentigo maligna.

DESIGN: Thirty one re-excision specimens for lentigo maligna were evaluated for R21 expression using previously published protocol. In addition, 153 cases including 41 lentigo malignas, 30 non-lentigo maligna-type melanomas, 38 lentigos, and 44 nevi were evaluated using a modified stringent protocol to eliminate all nonmelanocyte staining.

RESULTS: The sensitivity of nuclear staining with R21 in lentigo maligna was 87.8%. Nuclear expression of sAC was observed in 40% of other melanomas and 2.3% of benign nevi. R21 did not stain nuclei of resting melanocytes but was observed in 28.9% of melanocytic hyperplasias. These cases were easily distinguished from lentigo maligna in routine sections. R21 staining facilitated extent of the lesion in resection margins. In cases examined under the less stringent conditions, interpretation was facilitated by comparing R21 and Mart1/Melan A staining. Greater than 9 pan-nuclear staining melanocytes within one high-power field along with a pan-nuclear sAC/Melan A ratio greater than 0.5 was consistent with a positive margin whereas 5 or less pan-nuclear staining melanocytes along with a sAC/Melan A ratio of less than 0.3 constituted a negative margin.

CONCLUSION: R21 is a useful diagnostic adjunct in the diagnosis and evaluation of margins in re-excision specimens in lentigo maligna.

DOI10.5858/arpa.2011-0617-OA
Alternate JournalArch. Pathol. Lab. Med.
PubMed ID23194049
PubMed Central IDPMC3732207
Grant ListK08 CA160657 / CA / NCI NIH HHS / United States
1 K08 CA 160657-01 / CA / NCI NIH HHS / United States