Sources/Clones
Dako (E9).
Fixation/Preparation
Immunoreactive in fixed paraffin-embedded tissue sections as well as cell preparations and frozen sections. Immunoreactivity is enhanced following HIER.
Background
Metallothioneins (MTs) are low molecular weight, heavy metalbinding proteins whose expression is induced by heavy metals as well as other factors such as stress, glucocorticoids, lymphokines and xenobiotics (Kagi, 1993). MTs have been described in most vertebrate and invertebrate species. Two major isoforms, MT-I and MT-II, are distributed in most adult mammalian tissues. Recently, another isoform, MT-0, has been recognized and genes for MT-III and MT-IV with restriction to brain neurons and stratified epithelium have been described (Jasani & Schmid, 1997). Interest in MTs has focused on their overexpression and susceptibility to carcinogenic and anticarcinogenic effects of cadmium, spontaneous mutagenesis and anticancer drugs, and tumor resistance to chemotherapeutic agent (see Jasani & Schmid 1997).
Applications
The ability to stain for MTs with immunohistochemical methods has produced a large amount of data concerning their expression at different stages of development and progression of a wide variety of tumors. Briefly, overexpression of MT has been associated with the type and grade of some tumors such as ductal breast carcinoma (Oyama et al, 1996), skin carcinoma (Zelger et al, 1994), cervical carcinoma (Lim et al, 1996), pancreatic carcinoma (Ohshio et al, 1996), prostatic carcinoma (Zhang et al 1996), melanoma (Zelger et al, 1993) and acute lymphoblastic leukemia. While overexpression of MTs appears to be mostly associated with locally invasive carcinomas of poor histological type and grade, reduced overall survival and local recurrence of tumor (but not lymph node or distant metastases), this is not true of all tumors. In colonic (Gaiuffre et al, 1996), bladder (Saika et al, 1994; Bahnson et al, 1994) and fibroblastic skin tumors (Zelger et al, 1994), overexpression of MTs is associated with lower grade, better differentiated tumors. The reason for this apparent discrepancy is not clear. It has been suggested that current antibodies for immunostaining are unable to distinguish between MT-I and MT-II isoforms or metal-bound and metal-free (apoMT) forms of the protein. Furthermore, they are also unable to detect overexpression of MT-0, MT-III and MT-IV isoforms, accounting for the apparently conflicting observations (Jasani & Schmid, 1997). The use of MT expression to predict response to chemotherapy is another avenue which requires further study (Saika et al, 1994; Gaiuffre et al, 1996).
A recent paper describes MT as a marker of deep penetrating dermatofibroma, allowing its distinction from dermatofibrosarcoma protuberans, which was consistently negative by immunostaining (Zelger et al, 1994).
Comments
MT staining is found in both nucleus and cytoplasm and the proliferating edges of tumors show most intense staining (Cherian, 1994).
References
•Bahnson RR, Becich M, Ernstoff MS et al 1994. Absence of immunohistochemical metallothionein staining in bladder tumor specimens predicts response to immunohistochemical metallothionein staining in bladder tumor specimens predicts response to neoadjuvant cisplatin, methotrexate and vinblastine chemotherapy. Journal of Urology 152: 2272-2275.
•Cherian MG 1994. The significance of the nuclear and cytoplasmic localization of metallothionein in human liver and tumor cells. Environmental Health Perspectives 102: 131-135.
•Gauffre G, Barresi G, Sturniolo GC et al 1996. Immunohistochemical expression of metallothionein in normal human rectal mucosa, in adenomas, and in adenocarcinomas and their associated metastases. Histopathology 29:347-354.
•Jasani B, Schmid KW 1997. Significance of metallothionein overexpression in human tumors. Histopathology 31: 211-214.
•Kagi JHR 1993. Overview of methallothionein. Metallobiochemistry Part B: metallothionein and related molecules. Methods in Enzymology 205: 613-626.
•Lim K, Evans A, Adams M et al 1996. Association of immunohistochemically detectable metallothionein (IDMT) expression with malignant transformation in cervical neoplasia. Journal of Pathology 178 (suppl): 48A.
•Ohshio G, Imamura T, Okada N et al 1996. Immunohistochemical study of metallothionein in pancreatic carcinomas. Journal of Cancer Research and Clinical Oncology 122: 351-355.
•Oyama T, Take H, Hikino T et al 1996. Immunohistochemical expression of metallothionein in invasive breast cancer in relation to proliferative activity, histology and prognosis. Oncology 53: 112-117.
•Saika T, Tsushima T, Ochi J et al 1994. Over-expression of metallothionein and drug-resistance in bladder cancer. International Journal of Urology 1: 135-139.
•Zhang XH, Jin L, Sakamoto T, Takenaka I 1996. Immunohistochemical localization of metallothionein in human prostate cancer. Journal of Urology 156: 1679-1681.
•Zelger B, Sidoroff A, Hopfl R et al 1994. Metallothionein expression in nonmelanoma skin cancer. Applied Immunohistochemistry 2: 254-260.
•Zelger B, Hittmair A, Schir M et al 1993. Immunohistochemically demonstrated metallothionein expression in malignant melanoma. Histopathology 23: 257-264.
Bibliografia
Manual of diagnostic antibodies for immunohistology / Anthony S.-Y. Leong, Kumarasen Cooper, F. Joel W.-M. Leong.
Dako (E9).
Fixation/Preparation
Immunoreactive in fixed paraffin-embedded tissue sections as well as cell preparations and frozen sections. Immunoreactivity is enhanced following HIER.
Background
Metallothioneins (MTs) are low molecular weight, heavy metalbinding proteins whose expression is induced by heavy metals as well as other factors such as stress, glucocorticoids, lymphokines and xenobiotics (Kagi, 1993). MTs have been described in most vertebrate and invertebrate species. Two major isoforms, MT-I and MT-II, are distributed in most adult mammalian tissues. Recently, another isoform, MT-0, has been recognized and genes for MT-III and MT-IV with restriction to brain neurons and stratified epithelium have been described (Jasani & Schmid, 1997). Interest in MTs has focused on their overexpression and susceptibility to carcinogenic and anticarcinogenic effects of cadmium, spontaneous mutagenesis and anticancer drugs, and tumor resistance to chemotherapeutic agent (see Jasani & Schmid 1997).
Applications
The ability to stain for MTs with immunohistochemical methods has produced a large amount of data concerning their expression at different stages of development and progression of a wide variety of tumors. Briefly, overexpression of MT has been associated with the type and grade of some tumors such as ductal breast carcinoma (Oyama et al, 1996), skin carcinoma (Zelger et al, 1994), cervical carcinoma (Lim et al, 1996), pancreatic carcinoma (Ohshio et al, 1996), prostatic carcinoma (Zhang et al 1996), melanoma (Zelger et al, 1993) and acute lymphoblastic leukemia. While overexpression of MTs appears to be mostly associated with locally invasive carcinomas of poor histological type and grade, reduced overall survival and local recurrence of tumor (but not lymph node or distant metastases), this is not true of all tumors. In colonic (Gaiuffre et al, 1996), bladder (Saika et al, 1994; Bahnson et al, 1994) and fibroblastic skin tumors (Zelger et al, 1994), overexpression of MTs is associated with lower grade, better differentiated tumors. The reason for this apparent discrepancy is not clear. It has been suggested that current antibodies for immunostaining are unable to distinguish between MT-I and MT-II isoforms or metal-bound and metal-free (apoMT) forms of the protein. Furthermore, they are also unable to detect overexpression of MT-0, MT-III and MT-IV isoforms, accounting for the apparently conflicting observations (Jasani & Schmid, 1997). The use of MT expression to predict response to chemotherapy is another avenue which requires further study (Saika et al, 1994; Gaiuffre et al, 1996).
A recent paper describes MT as a marker of deep penetrating dermatofibroma, allowing its distinction from dermatofibrosarcoma protuberans, which was consistently negative by immunostaining (Zelger et al, 1994).
Comments
MT staining is found in both nucleus and cytoplasm and the proliferating edges of tumors show most intense staining (Cherian, 1994).
References
•Bahnson RR, Becich M, Ernstoff MS et al 1994. Absence of immunohistochemical metallothionein staining in bladder tumor specimens predicts response to immunohistochemical metallothionein staining in bladder tumor specimens predicts response to neoadjuvant cisplatin, methotrexate and vinblastine chemotherapy. Journal of Urology 152: 2272-2275.
•Cherian MG 1994. The significance of the nuclear and cytoplasmic localization of metallothionein in human liver and tumor cells. Environmental Health Perspectives 102: 131-135.
•Gauffre G, Barresi G, Sturniolo GC et al 1996. Immunohistochemical expression of metallothionein in normal human rectal mucosa, in adenomas, and in adenocarcinomas and their associated metastases. Histopathology 29:347-354.
•Jasani B, Schmid KW 1997. Significance of metallothionein overexpression in human tumors. Histopathology 31: 211-214.
•Kagi JHR 1993. Overview of methallothionein. Metallobiochemistry Part B: metallothionein and related molecules. Methods in Enzymology 205: 613-626.
•Lim K, Evans A, Adams M et al 1996. Association of immunohistochemically detectable metallothionein (IDMT) expression with malignant transformation in cervical neoplasia. Journal of Pathology 178 (suppl): 48A.
•Ohshio G, Imamura T, Okada N et al 1996. Immunohistochemical study of metallothionein in pancreatic carcinomas. Journal of Cancer Research and Clinical Oncology 122: 351-355.
•Oyama T, Take H, Hikino T et al 1996. Immunohistochemical expression of metallothionein in invasive breast cancer in relation to proliferative activity, histology and prognosis. Oncology 53: 112-117.
•Saika T, Tsushima T, Ochi J et al 1994. Over-expression of metallothionein and drug-resistance in bladder cancer. International Journal of Urology 1: 135-139.
•Zhang XH, Jin L, Sakamoto T, Takenaka I 1996. Immunohistochemical localization of metallothionein in human prostate cancer. Journal of Urology 156: 1679-1681.
•Zelger B, Sidoroff A, Hopfl R et al 1994. Metallothionein expression in nonmelanoma skin cancer. Applied Immunohistochemistry 2: 254-260.
•Zelger B, Hittmair A, Schir M et al 1993. Immunohistochemically demonstrated metallothionein expression in malignant melanoma. Histopathology 23: 257-264.
Bibliografia
Manual of diagnostic antibodies for immunohistology / Anthony S.-Y. Leong, Kumarasen Cooper, F. Joel W.-M. Leong.
