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Expression and Prognostic Value of -, ß-, and -Catenins in Differentiated Thyroid Carcinoma

Department of Pathology and Forensic Medicine (J.B., K.K., J.K., V.-M.K.), University of Kuopio and Kuopio University Hospital, FIN-70211 Kuopio; and Departments of Medicine and Clinical Nutrition (L.N.), Otorhinolaryngology , Oral and Maxillofacial Unit (J.K.), and Surgery (M.E., E.A.), Kuopio University Hospital, FIN-70211 Kuopio; and Department of Pathology (S.H.), Satakunta Central Hospital, FIN-28500 Pori, Finland

Address correspondence and requests for reprints to: Veli-Matti Kosma, M.D., Ph.D., Department of Pathology and Forensic Medicine, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland. E-mail: VeliMatti.Kosma{at}uku.fi

Catenins (, ß, and ) are a group of intracellular cell adhesion molecules that unite cytoskeleton with extracellular adhesion system. Abnormal expression of these molecules may have prognostic relevance in various carcinomas, including differentiated thyroid carcinoma (DTC). We have, therefore, evaluated the prognostic value of -, ß-, and -catenins along with traditional risk factors in 206 consecutive DTC patients by immunohistochemistry.

Papillary carcinomas showed normal staining pattern for -, ß-, and -catenins in 124 (60%), 136 (67%), and 94 (46%) cases, respectively. Follicular carcinomas expressed -, ß-, and -catenins normally in 16 (48%), 18 (55%), and 8 (32%) cases, respectively. Follicular type of tumor showed more often reduced staining for all catenins than papillary carcinoma (P = 0.009, P = 0.004, and P = 0.002, respectively). Age (>60 yr) and pTNM-stage were related to reduced - and ß-catenin expression levels (P = 0.027 and P = 0.026, respectively) and larger size of the tumor to reduced ß- and -catenin expressions (P = 0.039 and P = 0.007, respectively). Nodal metastases at the time of primary treatment related to reduced -catenin expression and distal metastases to reduced ß- and -catenin staining signals (P = 0.022, P = 0.014, and P = 0.039, respectively). Reduced -catenin associated with tumor recurrence (P = 0.002) and reduced ß-catenin with cancer-related mortality (P = 0.005). The multivariate analysis for recurrence-free survival showed that -catenin and serum thyroglobulin level 1 yr after primary treatment were prognostic of recurrent disease (hazards ratio, 3.42, P = 0.022; and hazards ratio, 10.03, P = 0.0001). In addition, -catenin retained its prognostic significance in low-stage patients (P = 0.0151). We propose that the evaluation of -catenin expression by immunohistochemistry in DTC patients has prognostic value in addition to that obtained by traditional prognostic factors.

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