Our results on the immunohistochemical NIS expression in normal thyroid and Graves’ disease (an autoimmune condition known to express high levels of NIS) (42) were in accordance to data previously reported (10, 12, 14, 17, 21), i.e., focal membrane expression of NIS in normal thyroid gland and a strong and widespread membrane NIS expression in Graves’ disease. The great difference observed in NIS expression between normal thyroid and in Graves’ disease may be considered as an example of how TSH is able to regulate NIS expression and the targeting to the membrane. Regarding carcinomas, we observed that the majority (71.6%) displayed NIS immunostaining, which is in accordance to the literature (13, 14, 17, 18, 19, 20, 21, 22, 23) (Table 4), but only a minority presented NIS in the basolateral membrane of tumor cells (5.7%). If one compares the percentage of cases with NIS plasma membrane staining, there are large differences between studies (Table 4). Such differences may be due to the variable size of the series and to differences in the antibodies used to perform the IHC (almost every study uses its own antibody, Table 4). In fact, one study compared NIS immunostaining using two different antibodies in a large series of thyroid carcinomas and observed some differences in the percentage of positive cells (29). To be sure that we were not missing any signal, we performed the IHC for NIS with TSA signal amplification in a subset of carcinomas with different immunostaining patterns and observed a complete vanish of intracytoplasmic staining and an amplification of the membrane staining. These results, like those from Peyrottes and coworkers (21) rise some questions about the real significance of NIS intracytoplasmic staining, so we decided to perform our analysis considering positive only the cases with membrane staining. Table 4Bibliographic revision and present results of NIS protein evaluation by IHC in thyroid carcinomas.ReferenceNo. of carcinomasAnti-NIS antibodies used in the studyNegative cases (%)Positive cases (%)*Cases with membrane staining (%)**(26)4 DTCsProduced by authors(10)14 DTCsProduced by authorsDescriptive studies(11)12 PTCsProduced by authors(12)9 DTCsProduced by authors(13)60 DTCsClone FP-1326.773.3N/A(14)57 (53 DTCs; 2 ATC; 2 MTC)Produced by authors29.870.215.8(15)67 DTCsDonated by Dr SM Jhiang of Ohio State University, USA67.232.8N/A(17)90 (87 DTCs; 3 ATC)Produced by authors22.577.5Some(24) 67 PTCsPohlenz et al. (2000)N/ASome(18)17 PTCsClone Ab-1010058.8(19)40 PTCsBrahms Diagnostica GmbH, Berlin, Germany010052.5(20)29 (25 DTCs; 4 ATC)Clone FP5A37.562.5N/A(21)47 (42 DTCs; 5MTC)Clones 39S, Ab-1 and FP5A49510(25)50 PTCsTazebay et al. (2000)N/A8(22)32 DTCsZhongshan Goldbridge Biotechnology, Beijin China010018.8(1)#265 DTCsClone FP5A881212(29)#380 (283 DTCs; 97 ATCs)Donated by N. Morgenthaler (Brahms Diagnostics, Henningsdorf, Germany)87.412.612.6(23)370 PTCsClone SPM18632.767.30.8(present study)211 (199 DTCs; 12 PDTCs)Clone FP5A28.471.65.7*Percentage of positive cases (independently of the cellular location); **percentage of cases with NIS membrane staining with or without simultaneous cytoplasmic staining; #these specific studies only considered positive cases with membrane staining.ATC, anaplastic thyroid carcinoma; MTC, medullary thyroid carcinoma; N/A, not addressed; PDTC, poorly differentiated thyroid carcinoma.