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

Arch Pathol Lab Med. 2012 Dec;136(12):1558-64. doi: 10.5858/arpa.2011-0617-OA.


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.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adenylyl Cyclases / chemistry
  • Adenylyl Cyclases / metabolism*
  • Antibodies, Monoclonal / metabolism*
  • Antibodies, Monoclonal, Murine-Derived
  • Antibody Specificity
  • Biomarkers, Tumor / chemistry
  • Biomarkers, Tumor / metabolism*
  • Cell Nucleus / enzymology
  • Cell Nucleus / metabolism
  • Cell Nucleus / pathology
  • Diagnosis, Differential
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hutchinson's Melanotic Freckle / diagnosis
  • Hutchinson's Melanotic Freckle / metabolism*
  • Hutchinson's Melanotic Freckle / pathology
  • Hutchinson's Melanotic Freckle / surgery
  • Hyperplasia
  • Immunohistochemistry
  • MART-1 Antigen / metabolism
  • Melanocytes / enzymology
  • Melanocytes / metabolism
  • Melanocytes / pathology
  • Melanoma / diagnosis
  • Melanoma / metabolism
  • Melanoma / pathology
  • Melanoma / surgery
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / metabolism*
  • Nevus / diagnosis
  • Nevus / metabolism
  • Nevus / pathology
  • Nevus / surgery
  • Sensitivity and Specificity
  • Skin / enzymology*
  • Skin / metabolism
  • Skin / pathology
  • Skin Neoplasms / diagnosis
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / pathology
  • Skin Neoplasms / surgery
  • Solubility


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Biomarkers, Tumor
  • MART-1 Antigen
  • Neoplasm Proteins
  • R21 monoclonal antibody
  • Adenylyl Cyclases