Axcel/Accurate (polyclonal), Biodesign (polyclonal), Biogenesis (polyclonal, 1I5), Biogenex (polyclonal), Caltag Laboratories (polyclonal), Chemicon (polyclonal), Dako (polyclonal, CAL-3-F5), Fitzgerald (polyclonal), Immunotech (polyclonal), Sanbio/Monosan (polyclonal), Seralab (polyclonal) and Zymed (polyclonal).

These antibodies are applicable to formalin-fixed paraffin sections. HIER does not appear to enhance immunoreactivity but is not deleterious.

CAL-3-F5 was raised against the synthetic peptide corresponding to the C-terminal portion of human calcitonin (aa 24-32). The polyclonal antibodies were raised in rabbits using synthetic human calcitonin (35 kD). Molecular biology studies have shown that most regulatory peptides are cleavage products of larger precursor molecules (Sikri et al, 1985). The structure of the calcitonin precursor was predicted from the nucleotide sequence of cloned cDNA prepared from the mRNA obtained from medullary thyroid carcinoma (Allison et al, 1981; Amara et al, 1982a). In the human calcitonin precursor, calcitonin is flanked by two molecules: PDN (peptide-aspartic acid-asparagine), a 21-amino acid C-terminal flanking peptide, and a larger N-terminal peptide. Calcitonin gene-related peptide (CGRP)a is also encoded by the calcitonin gene and is produced as a result of differential RNA processing (Amara et al, 1982b). The differential production of CGRP and calcitonin from the calcitonin gene is regulated in a tissue-specific manner, with CGRP being produced in nervous tissue and calcitonin in thyroid C-cells. However, both CGRP and calcitonin is found in normal, hyperplastic and neoplastic C-cells in man, although the immunohistochemical pattern of localization is different for individual antigens.

Antibodies to calcitonin are useful to identify normal, hyperplastic and neoplastic C-cells. Medullary thyroid carcinoma (MTC) occurs in both a sporadic and inherited form, with a biological behavior between anaplastic and differentiated thyroid carcinomas. Given the morphologic heterogeneity of MTC, both in histological structure (solid, trabecular or insular) and cellular patterns (spindle, polyhedral, angular or round), as well as the description of papillary, follicular, clear cell and anaplastic variants (SchrÕder et al, 1988), the role of antibodies to calcitonin becomes crucial in making the correct diagnosis. All MTC in a series of 60 (SchrÕder et al, 1988) and 25 (Sikri et al, 1985) cases demonstrated immunoreaction with antibodies to calcitonin. It has also been suggested that calcitonin-rich tumors appeared to have a better prognosis than calcitonin-poor neoplasms (Saad et al, 1984). However, subsequent studies were at variance with these observations (SchrÕder et al, 1988). Studies have also shown sporadic MTC to be a more life-threatening neoplasm than MTC occurring in the setting of MFN II a syndrome, whilst MEN IIb syndrome was most aggressive. Finally, antibodies to calcitonin are useful to identify the concept of C-cell hyperplasia in benign and malignant thyroid glands (Santeusanio et al, 1997).

Antibody to calcitonin is a compulsory addition to any immunohistochemical histopathology laboratory for the diagnosis of MTC. Normal parafollicular C-cells are suitable as positive control tissue.

•Allison J, Hall L, MacIntyre I, Craig RK 1981. The construction and partial characterisation of plasmids containing complementary DNA sequences to human calcitonin precursor polyprotein. Biochemistry Journal 199: 725-731.

•Amara SG, Jonas V, O'Neil JA et al 1982a. Calcitonin COOH-terminal cleavage peptide as a model for identification of novel neuropeptides predicted by recombinant DNA analysis. Journal of Biology and Chemistry 257: 2129-2132.

•Amara SG, Jonas V, Rosenfeld MG, Ong ES, Evans RM 1982b. Alternative RNA processing in calcitonin gene expression generates mRNAs encoding different polypeptide products. Nature 298:240-244.

•Saad MF, Ordonez NG, Guido JJ, Samaan NA 1984. The prognostic value of calcitonin immunostaining in medullary carcinoma of the thyroid. Journal of Clinical Endocrinology and Metabolism 59:850-856.

•Santeusanio G, Iafrate E, Partenzi A et al 1997. A critical reassessment of the concept of C-cell hyperplasia of the thyroid. Applied Immunohistochemistry 5: 160-172.

•SchrÕder S, BÓker W, Baisch H et al 1988. Prognostic factors in medullary thyroid carcinomas. Survival in relation to age, sex, stage, histology, immunocytochemistry, and DNA content. Cancer 61:806-816.

•Sikri KL, Varndell IM, Hamid QA et al 1985. Medullary carcinoma of the thyroid. An immunocytochemical and histochemical study of 25 cases using eight separate markers. Cancer 56:2481-2491.

Manual of diagnostic antibodies for immunohistology / Anthony S.-Y. Leong, Kumarasen Cooper, F. Joel W.-M. Leong.