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Immunohistochemical Profile of the Sodium/Iodide Symporter in Thyroid, Breast, and Other Carcinomas Using High Density Tissue Microarrays and Conventional Sections

Departments of Surgery (I.L.W., R.S.G.) and Pathology (M.v.d.R., K.N., K.M.), Stanford University School of Medicine, Stanford, California 94305-5655; Department of Pathology and Laboratory Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School (P.S.A., K.W.), New Brunswick, New Jersey 08903; and Department of Molecular Pharmacology, Albert Einstein College of Medicine (O.D., N.C.), Bronx, New York 10461

Address all correspondence and requests for reprints to: Irene L. Wapnir, M.D., Department of Surgery, Stanford University School of Medicine, 300 Pasteur Drive, H-3625, Stanford, California 94305-5655. E-mail: wapnir{at}stanford.edu.

Extrathyroidal cancers could potentially be targeted with ¹³¹I, if the Na⁺/I^- symporter (NIS) were functional. Using immunohistochemical methods we probed 1278 human samples with anti-NIS antibody, including 253 thyroid and 169 breast conventional whole tissue sections (CWTS). Four high density tissue microarrays containing a wide variety of breast lesions, normal tissues, and carcinoma cores were tested. The results of the normal microarray were corroborated in 50 CWTS. Nineteen of 34 normal tissues, including bladder, colon, endometrium, kidney, prostate, and pancreas, expressed NIS. Nineteen of 25 carcinomas demonstrated NIS immunopositivity; 55.7% of 479 carcinoma microarray cores expressed NIS, including prostate (74%), ovary (73%), lung (65%), colon (62.6%), and endometrium (56%). NIS protein was present in 75% benign thyroid lesions, 73% thyroid cancers, 30% normal-appearing, peritumoral breasts, 88% ductal carcinomas in situ, and 76% invasive breast carcinoma CWTS. Comparatively, breast microarray cores had lower immunoreactivity. Plasma membrane immunopositivity was confirmed in thyrocytes, salivary ductal, gastric mucosa, and lactating mammary cells. In other tissues, immunoreactivity was predominantly intracellular, particularly in malignant lesions. Thus, NIS is present in many normal epithelial tissues and is predominantly expressed intracellularly in many carcinomas. Elucidating the regulatory mechanisms that render NIS functional in extrathyroidal carcinomas may make ¹³¹I therapy feasible.

This work was supported in part by the Susan G. Komen Breast Cancer Foundation (Grant IMG 99-003052, to I.L.W.; and Grant 99-003136, to N.C.), the Mary Kay Ash Charitable Foundation (Grant 028-02, to N.C.), and NIH Grant DK-41544 (to N.C.).

Abbreviations: Ab, Antibody; CSA, catalyzed signal amplification protocol; CWTS, conventional whole tissue sections; DTC, differentiated thyroid cancer; NIS, Na⁺/I^- symporter.

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