Melanocytic Tumors Express Connexin 43 but Not 26, a Immunohistochemical Analysis in Histologic Materials and Potential Significance of the Findings in Melanocytic Oncogenesis
RH Gormley, T Pasha, H Niu, G Acs, X Xu, PJ Zhang. University of Pennsylvania, Philadelphia, PA; H. Lee Moffitt Cancer Center & Research Institute, Tempa
Background: Connexins (Cx) are major molecular components of gap junctions vital to cell-cell communication which regulates cell proliferation and death. Cx are thought to have tumor suppressor function. However, there is also mounting evidence to suggest that increased expression of some connexins, particularly Cx26, might increase invasive or metastatic properties of the tumor. The exact role of various connexins in melanocytic oncogenesis remains controversial. Our study examined Cx43 and Cx26 in a series of nevi and melanomas (MM) on routine surgical specimen.
Design: Formalin-fixed paraffin-embedded sections of 26 histologically well-characterized melanocytic lesions, 13 primary MM and 13 nevi, were stained with monoclonal antibody to Cx43 (clone CXN-6, 1:250) and polyclonal to Cx26 (1:100). Immunoreactivity in tumor cells was evaluated semi-quantitatively 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. The level of immunoreactivity for nevi vs. MM was then analyzed.
Results: Significantly higher Cx43 immunoreactivity was detected in MM (mean score 242) than in nevi (mean score 111) (p=0.002 Mann-Whitney). Both MM and nevi expressed minimal or entirely absent Cx 26 immunoreactivity. Staining patterns for both Cx26 and Cx43 were generally punctuate and membranous, but some cells showed a granular cytoplasmic pattern.
Conclusions: The finding of minimal or entirely absent Cx26 reactivity in this series was consistent with some previous studies showing absence of Cx26 expression in nevi and MM but not with others demonstrating increased Cx26 staining at sites of tumor invasion. Most notably, however, is the increased Cx43 staining seen in MM and nevi which is in contrast to results from previous studies reporting reduced or absent expression of Cx43 in nevi and MM. The significantly higher Cx43 level in MM when compared to nevi suggests a oncogenic role of Cx43 in melanocytic tumor progression. It is unclear if this discrepancy is due to the different study models used (clinicopathologic study vs more bench research). Nevertheless, our results failed to confirm the previous research finding and call into question established paradigms for the role of Cx43 in melanocytic oncogenesis.
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 47, Wednesday Morning