Reduced Cx43 Gap Junction Plaque Expression Differentiates Thyroid Carcinomas From Benign Disease

Objective: To investigate the expression of connexin 43 (Cx43) in benign vs malignant thyroid tissue for potential use as a diagnostic marker. Design: Retrospective study. Subjects: Thyroid specimens were obtained from 50 patients who underwent partial or total thyroidectomy at the New York Eye and Ear Infirmary, New York, New York, between 1999 and 2007. They included goiter (n = 5), follicular adenoma (n = 15), follicular carcinoma (n = 17), papillary thyroid carcinoma (PTC) (n = 7) and the follicular variant of PTC (n = 6). Interventions: Tissue sections (5 mu m) were immunohistochemically stained for Cx43 with the avidin-biotin-peroxidase method using an automated stainer. The Cx43 membrane staining pattern was evaluated. Results: Twenty-three of 30 cancer specimens (77%) revealed a loss of Cx43 plaque staining at the cellular membrane compared with only 3 of 20 benign specimens (15%). Among the malignant specimens, loss of Cx43 plaque staining was observed in 11 of 17 follicular carcinomas (65%), 5 of 6 follicular variants of PTC (83%), and 7 of 7 PTCs (100%). In contrast, only 3 of 15 adenomas (20%) and 0 of 5 goiter samples demonstrated loss of Cx43 plaque staining at the cell membrane. Conclusion: Our data provide evidence that the absence of Cx43 plaque staining is associated with thyroid cancer and thus holds potential clinical utility as a marker for malignant disease.