Secretogranin IV immunoreactivity in medullary thyroid carcinoma: an immunohistochemical study of 62 cases.

The presence and intracellular distribution of secretogranin IV (Sg IV) was determined on light microcop by the avidin-biotin peroxidase complex method with the monoclonal antibody (mAb) Hisl-19 in normal and hyperplastic C-cells, in 62 primary medullary thyroid carcinomas (MTCs) and in 17 MTCs in tissue from synchronous and/or metachronous lymph node metastases and in one liver metastasis. Sg IV immunoreactivity was present in almost all normal-looking and hyperplastic C-cells, in 59 of 62 (96%) of the primary tumours, in 18 of 26 (69%) lymph node metastases and in distant metastasis. Sg IV reactivity ranged from small foci of positive tumour cells to a reaction in virtually every malignant cell. Two different staining patterns were obvious: a granular cytoplasmic reactivity and a perinuclear cluster-type signal. Normal-appearing and hyperplastic C-cells were characterized by a uniform granular staining often coexisting with discrete cluster-type immunoreactivity. Various combinations of these staining patterns were observed in C-cell carcinomas. The pure cluster-type reactivity was restricted to malignant C cells and was not detected in normal-appearing and hyperplastic C-cells. In serial sections immunohistochemical results for Sg IV, calcitonin (Ct) and chromogranin A (Cg A) showed only partial correlation. Depending on the area of the tumour chosen, immunohistochemical reactivity for Ct and Cg A might not be demonstrated in neoplastic C-cells, while staining for Sg IV was retained. The amount and type of Sg IV reactivity of MTCs was not correlated with the biological behaviour of the tumours. These results indicate that mAb Hisl-19 is an excellent marker for normal, hyperplastic and neoplastic C-cells. MAb Hisl-19 is especially useful in cases with weak or questionable reactivity for Ct and Cg A. The switch from the granular pattern to the perinuclear distribution seems to indicate a malignant transformation of C-cells and might prove useful an an additional diagnostic clue.