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Melanocytic Tumors Express Connexin 43 but not 26: Immunohistochemical Analysis With Potential Significance in Melanocytic Oncogenesis

Sargen, Michael R. BA*; Gormley, Rachel H. MD*; Pasha, Terri L. BS*; Yum, Sabrina MD; Acs, Geza MD; Xu, Xiaowei MD, PhD*; Zhang, Paul J. MD*

The American Journal of Dermatopathology: December 2013 - Volume 35 - Issue 8 - p 813–817
doi: 10.1097/DAD.0b013e318278d401
Original Study

Abstract: Connexins (Cx) are structural proteins that form gap junctions, which are vital to cell–cell communication and help to regulate cell division. The purpose of this study was to evaluate if there are diagnostically important differences in immunostaining for connexins 43 (Cx43) and 26 (Cx26) in melanoma compared with nevi. Formalin-fixed paraffin-embedded sections of 34 histologically well-characterized melanocytic lesions, 17 primary malignant melanomas (MM), and 17 nevi were stained with a polyclonal antibody to Cx43 and a polyclonal antibody to Cx26. Immunoreactivity in tumor cells was evaluated semiquantitatively based on extent (1%–100%) and intensity (0–3) of reactivity. A score of 0–300 was generated by the product of the extent and intensity readings in each case. Significantly higher Cx43 immunoreactivity was detected in MM (mean intensity score = 253.5; 95% confidence interval, 227.9–279.2; P = 0.002) compared with nevi (mean intensity score = 152.4; 95% confidence interval, 104.9–199.8). In contrast, Cx26 immunoreactivity was less than 5% or entirely absent in all melanocytic tumors (n = 34). The significantly higher Cx43 staining in MM when compared with nevi suggests an oncogenic role for this protein in melanocytic tumor progression. Consequently, the evaluation of immunohistochemical staining for Cx43 in conjunction with other ancillary stains and tumor histology may be helpful in distinguishing MM from nevi, although positive Cx26 reactivity suggests that a cutaneous neoplasm is of nonmelanocytic origin.

*Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA

Department of Neurology, Children Hospital of Philadelphia, Philadelphia, PA

Department of Pathology, Moffitt Cancer Center, Tampa, FL.

Reprints: Paul J. Zhang, MD, Department of Pathology and Laboratory Medicine, University of Pennsylvania, 6 Founders Building, 3400 Spruce Street, Philadelphia, PA 19104 (e-mail:

With respect to design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the article, this study was funded by the University of Pennsylvania, Department of Pathology and Laboratory Medicine Anatomic Pathology Research Fund.

The authors have no relevant conflicts of interest concerning the content or message of this article.

M. R. Sargen and R. H. Gormley contributed equally to this project.

© 2013 by Lippincott Williams & Wilkins.