Ferritin

Sources/Clones
American Qualex (polyclonal), American Research Products (047A1703), Axcel/Accurate (polyclonal), Biodesign (ME.110, S1, S2, 501, 502, 503, 504, polyclonal), Biogenesis (05, 7D3/7, polyclonal), Biogenex (M3.170, polyclonal), Chemicon (polyclonal), Dako (polyclonal), Fitzgerald (M94156, M94157, M94159, M94160, M94212, M94258, polyclonal), Serotec (polyclonal) and Zymed (ZMFE1).

Fixation/Preparation
Ferritin is resistant to formalin fixation and immunoreactivity is enhanced following HIER.

Background
Ferritin, the iron storage protein, plays a key role in iron metabolism and its ability to sequester iron gives ferritin the dual functions of iron detoxification and iron reserve. The distribution of ferritin is ubiquitous among living species and its three-dimensional structure is highly conserved. All ferritins have 24 protein subunits arranged in 432 symmetry to give a hollow shell with an 80 A diameter cavity capable of storing up to 45000 Fe (III) atoms as an inorganic complex. Subunits are folded as four-helix bundles each having a fifth short helix at roughly 60 to the bundle axis (Harrison & Arosio, 1996).

Applications
Ferritin was one of the first markers employed for the identification of hepatocytes and their neoplastic counterparts (Imoto et al, 1985; Johnson et al, 1992), but it proved to be of low sensitivity and low specificity, being found in a wide range of benign and neoplastic tissues (Fleming, 1987; Pennys & Zlatkiss, 1990; Tuccari et al, 1992; Momotani et al, 1992). Ferritin is expressed in hepatoid tumors such as those in the ovary (Nogales et al, 1993) and hepatoblastomas (Abenoza et al, 1987). It is employed as a marker of hemorrhage in the brain (Carter et al, 1991; Ozawa et al, 1994) and as a marker of microglia (Kaneko et al, 1989). In bone marrow biopsies, ferritin has been found to correlate with marrow hemosiderin as detected by the Perl's stain and is advocated as a more sensitive tool for the evaluation of body iron stores (Navone et al, 1988). In the skin, ferritin is localized to the outer layer of the eccrine duct and in sweat gland neoplasms, two distinct patterns were noted. In syringoma the antibody decorated the outermost layer of cells in the epithelial cords of the tumor so that a characteristic ring was produced in cross-sections whereas only sparse staining was observed with other eccrine duct tumors such as dermal duct tumor and eccrine poroma. Syringoma showed diffuse staining, as did acrospiroma and a number of other adnexal carcinomas (Penneys & Zlatkiss, 1990).

Comments
The diagnostic applications of this marker are limited and, except perhaps for the assessment of bone marrow iron stores, ferritin is never employed alone.

References
•Abenoza P, Manivel JC, Wick MR et al 1987. Hepatoblastoma: an immunohistochemical and ultrastructural study. Human Pathology 18: 1025-1035.

•Carter RL, Hall JM, Corbett RP 1991 Immunohistochemical staining for ferritin in neuroblastomas. Histopathology 18: 465-468.

•Fleming S 1987 Immunocytochemical localization of ferritin in the kidney and renal tumors. European Urology 13: 407-411. Urology 13: 407-411.

•Harrison PM, Arosio P 1996 The ferritins: molecular properties, iron storage function and cellular regulation. Biochemia Biophysiologica Acta 1275: 161-203.

•Imoto M, Nishimura D, Fukuda Y et al 1985 Immunohistochemical detection of alpha-fetoprotein, carcinoembryonic antigen, and ferritin in formalin-fixed sections from hepatocellular carcinoma. American Journal of Gastroenterology 80: 902-906.

•Johnson DE, Powers CN, Rupp G et al 1992. Immunocytochemical staining of fine needle aspiration biopsies of the liver as a diagnostic tool for hepatocellular carcinoma. Modern Pathology 5: 117-123.

•Kaneko Y, Kitamoto T, Tateishi J, Yamaguchi K 1989 Ferritin immunohistochemistry as a marker for microglia. Acta Neuropathologica (Berlin) 79: 129-136.

•Momotani E, Wuscger N, Ravisse P, Rastogi N 1992. Immunohistochemical identification of ferritin, lactoferrin and transferrin in leprosy lesions of human skin biopsies.

•Journal of Comparative Pathology 106: 213-220.

•Navone R, Azzoni L, Valente G 1988 Immunohistochemical assessment of ferritin in bone marrow trephine biopsies: correlation with marrow hemosiderin. Acta Hematologica 80: 194-198.

•Nogales FF, Concha A, Plata C, Ruiz-Avila I 1993 Granulosa cell tumor of the ovary with diffuse true hepatic differentiation simulating stromal luteinization. American Journal of Surgical Pathology 17: 85-90.

•Ozawa H, Nishida A, Mito T, Takashima S 1994 Immunohistochemical study of ferritin-positive cells in the cerebellar cortex with subarachnoid hemorrhage in neonates. Brain Research 65: 345-348.

•Penneys NS, Zlatkiss I 1990 Immunohistochemical demonstration of ferritin in sweat gland and sweat gland neoplasms. Journal of Cutaneous Pathology 17: 32-36.

•Tuccari G, Rizzo A, Crisafulli C, Barresi G 1992 Iron-binding proteins in human colorectal adenomas and carcinomas: an immunohistochemical investigation. Histology and Histopathology 7: 543-547.

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