Sources/Clones
Accurate (polyclonal), Axcel/Accurate (polyclonal), Biodesign (polyclonal), Biogenesis (C5), Biogenesis/Novocastra (C5, polyclonal), Biogenex (C5, M1G8, polyclonal), Calbiochem (polyclonal), Caltag Laboratories (NCL-CDm), Chemicon (polyclonal), Dako (polyclonal), Fitzgerald (polyclonal), Immunotech (C5), Lab Vision Corp (C5), Novocastra (polyclonal), Oncogene (OS13A) and Zymed (polyclonal).
Fixation/Preparation
The antigen is immunoreactive in fixed, paraffin-embedded tissue sections only following HIER. Staining can also be performed on frozen sections and cell preparations.
Background
The cathepsins are ubiquitous lysosomal proteases and are classified both functionally and according to their active site. Cathepsin D, cathepsin B and, to a lesser extent, other cathepsins have been described as prognostic markers in cancer. Cathepsin D is the most widely studied of the cathepsins. It is an estrogen-regulated protease. A precursor form of 52 kD is processed in lysosomes into the mature 14 kD and 34 kD forms. This enzyme is thought to have proteolytic activity, which may facilitate the spread of neoplastic cells through different mechanisms and at different levels of the metastatic cascade. Cathepsin D is thought to promote tumor cell proliferation by acting as an autocrine mitogen through the activation of latent forms of growth factors or by interacting with growth factor receptors. The enzyme has also been shown, in vitro, to degrade extracellular matrix and to activate latent precursor forms of other proteinases involved in the invasive steps of the cancer metastasis. Although its active role in promoting these processes in vivo has yet to be proven, recent clinical observations which show a positive correlation between levels of cathepsin D activity and malignant progression of some human neoplasms further support this hypothesis (Duffy 1992; Leto et al, 1992). Cathepsin B, which catalyzes the degradation of laminin, may also play a role in the rupture of the basal membrane and may be of relevance in colorectal and pancreatic cancer (Schwartz, 1995).
Immunohistochemical studies in breast cancer have found that cathepsin D expression was significantly associated with poor overall survival in node-positive (Aaltonen et al, 1995) and node-negative patients (Isola et al, 1993). Recent observations that high levels of cathepsin D activity may be observed in macrophage-like stromal cells may account for some of the previous apparently conflicting reports concerning the prognostic relevance of biochemical and immunohistochemical estimations of cathepsin D in breast cancers. Cytosol assays measured total cathepsin D levels, whereas the immunohistochemical assessment was restricted to enzyme expression within tumor cells (Razumovic et al, 1997). When stromal cathepsin D levels were taken into account in immunohistochemical studies, significant associations were found with high tumor grade, increased tendency to local recurrence, regional recurrence, poorer disease-free survival and poorer overall patient survival (O'Donoghue et al, 1995; Joensuu et al, 1995; Charpin et al, 1997).
Applications
Cathepsin D expression has been studied in a variety of other tumors including carcinomas of the lung (Sloman et al, 1996; Higashiyama et al, 1997), stomach (Allgayer et al, 1997), uterine cervix (Kristensen et al, 1996), endometrium (Losch et al, 1996) and urinary bladder (Dickinson et al, 1995), medullary carcinoma of the thyroid (Holm et al, 1995) and colorectal cancer (Theodoropoulos et al, 1997).
Comments
Cathepsin D has recently been advocated as a marker of immature ganglion cells in suspected cases of Hirschsprung's disease, the intense granular cytoplasmic reactivity for the enzyme forming a collarette around the nucleus (Abu-Alfa et al, 1997).
References
•Aaltonen M, Lipponen P, Kosma VM et al 1995. Prognostic value of cathepsin-D expression in female breast cancer. Anticancer Research 15: 1033-1037.
•Abu-Alfa AK, Kuan SF, West AB, Reyes-Mugica M 1997. Cathepsin D in intestinal ganglion cells. A potential aid to diagnosis in suspected Hirschsprung's disease. American Journal of Surgical Pathology 21: 201-205.
•Allgayer H, Babic R, Grutzner KU et al 1997. An immunohistochemical assessment of cathepsin D in gastric carcinoma: its impact on clinical prognosis. Cancer 80: 179-187.
•Charpin C, Garcia S, Bouvier C et al 1997. Cathepsin D detected by automated and quantative immunohistochemistry in breast carcinomas: correlation with overall and disease free survival. Journal of Clinical Pathology 50: 586-590.
•Dickinson AJ, Fox SB, Newcomb PV et al 1995. An immunohistochemical and prognostic evaluation of cathepsin D expression in 105 bladder carcinomas. Journal of Urology 154: 237-241.
•Duffy MJ 1992. The role of proteolytic enzymes in cancer invasion and metastasis. Clinical and Experimental Metastasis 10: 145-155.
•Higashiyama M, Doi O, Kodama K et al 1997. Influence of cathepsin D expression in lung adenocarcinoma on prognosis: possible importance of its expression in tumor cells and stromal cells, and its intracellular polarization in tumor cells. Journal of Surgical Oncology 65: 10-19.
•Holm R, Hoie J, Kaalhus O, Nesland JM 1995. Immunohistochemical detection of nm23/NDP kinase and cathepsin D in medullary carcinomas of the thyroid gland. Virchows Archives 427: 289-294.
•Isola J, Weitz S, Visakorpi T, et al 1993. Cathepsin D expression detected by immunohistochemistry has independent prognostic value in node-negative breast cancer. Journal of Clinical Oncology 11: 36-43.
•Joensuu H, Toikkanen S, Isola J 1995. Stromal cell cathepsin D expression and long-term survival in breast cancer. British Journal of Cancer 71: 155-159.
•Kristensen GB, Holm R, Abeler VM, Trope CG 1996. Evaluation of the prognostic significance of cathepsin D, epidermal growth factor receptor, and c-erB-2 in early cervical squamous cell carcinoma. An immunohistochemical study. Cancer 78: 433-440.
•Leto G, Gebbia N, Rausa L, Tumminello FM 1992. Cathepsin D in the malignant progression of neoplastic diseases (review). Anticancer Research 12: 235-240.
•Losch A, Kohlberger P, Gitsch G et al 1996. Lysosomal protease cathepsin D is a prognostic marker in endometrial cancer. British Journal of Cancer 73: 1525-1528.
•O'Donoghue AE, Poller DN, Bell JA et al 1995. Cathepsin D in primary breast carcinoma: adverse prognosis is associated with expression of cathepsin D in stromal cells. Breast Cancer Research and Treatment 33: 137-145. prognosis is associated with expression of cathepsin D in stromal cells. Breast Cancer Research and Treatment 33: 137-145.
•Razumovic JJ, Stojkovic RR, Petrovecki M, Gamulin S 1997. Correlation of two methods for determination of cathepsin D in breast carcinoma (immunohistochemistry and ELIZA in cytosol). Breast Cancer Research and Treatment 43: 117-122.
•Schwartz MK 1995. Tissue cathepsins as tumor markers. Clinical Chimia Acta 237: 67-78.
•SlomanA, D'Amico F, Yousem SA 1996. Immunohistochemical markers of prolonged survival in small cell carcinoma of the lung. An immunohistochemical study. Archives of Pathology and Laboratory Medicine 120: 465-472.
•Theodoropoulos GE, Panoussopoulos D, Lazaris AC, Golematis BC 1997. Evaluation of cathepsin D immunostaining in colorectal adenocarcinoma. Journal of Surgical Oncology 5: 242-248.
Bibliografía
Manual of diagnostic antibodies for immunohistology / Anthony S.-Y. Leong, Kumarasen Cooper, F. Joel W.-M. Leong.
Accurate (polyclonal), Axcel/Accurate (polyclonal), Biodesign (polyclonal), Biogenesis (C5), Biogenesis/Novocastra (C5, polyclonal), Biogenex (C5, M1G8, polyclonal), Calbiochem (polyclonal), Caltag Laboratories (NCL-CDm), Chemicon (polyclonal), Dako (polyclonal), Fitzgerald (polyclonal), Immunotech (C5), Lab Vision Corp (C5), Novocastra (polyclonal), Oncogene (OS13A) and Zymed (polyclonal).
Fixation/Preparation
The antigen is immunoreactive in fixed, paraffin-embedded tissue sections only following HIER. Staining can also be performed on frozen sections and cell preparations.
Background
The cathepsins are ubiquitous lysosomal proteases and are classified both functionally and according to their active site. Cathepsin D, cathepsin B and, to a lesser extent, other cathepsins have been described as prognostic markers in cancer. Cathepsin D is the most widely studied of the cathepsins. It is an estrogen-regulated protease. A precursor form of 52 kD is processed in lysosomes into the mature 14 kD and 34 kD forms. This enzyme is thought to have proteolytic activity, which may facilitate the spread of neoplastic cells through different mechanisms and at different levels of the metastatic cascade. Cathepsin D is thought to promote tumor cell proliferation by acting as an autocrine mitogen through the activation of latent forms of growth factors or by interacting with growth factor receptors. The enzyme has also been shown, in vitro, to degrade extracellular matrix and to activate latent precursor forms of other proteinases involved in the invasive steps of the cancer metastasis. Although its active role in promoting these processes in vivo has yet to be proven, recent clinical observations which show a positive correlation between levels of cathepsin D activity and malignant progression of some human neoplasms further support this hypothesis (Duffy 1992; Leto et al, 1992). Cathepsin B, which catalyzes the degradation of laminin, may also play a role in the rupture of the basal membrane and may be of relevance in colorectal and pancreatic cancer (Schwartz, 1995).
Immunohistochemical studies in breast cancer have found that cathepsin D expression was significantly associated with poor overall survival in node-positive (Aaltonen et al, 1995) and node-negative patients (Isola et al, 1993). Recent observations that high levels of cathepsin D activity may be observed in macrophage-like stromal cells may account for some of the previous apparently conflicting reports concerning the prognostic relevance of biochemical and immunohistochemical estimations of cathepsin D in breast cancers. Cytosol assays measured total cathepsin D levels, whereas the immunohistochemical assessment was restricted to enzyme expression within tumor cells (Razumovic et al, 1997). When stromal cathepsin D levels were taken into account in immunohistochemical studies, significant associations were found with high tumor grade, increased tendency to local recurrence, regional recurrence, poorer disease-free survival and poorer overall patient survival (O'Donoghue et al, 1995; Joensuu et al, 1995; Charpin et al, 1997).
Applications
Cathepsin D expression has been studied in a variety of other tumors including carcinomas of the lung (Sloman et al, 1996; Higashiyama et al, 1997), stomach (Allgayer et al, 1997), uterine cervix (Kristensen et al, 1996), endometrium (Losch et al, 1996) and urinary bladder (Dickinson et al, 1995), medullary carcinoma of the thyroid (Holm et al, 1995) and colorectal cancer (Theodoropoulos et al, 1997).
Comments
Cathepsin D has recently been advocated as a marker of immature ganglion cells in suspected cases of Hirschsprung's disease, the intense granular cytoplasmic reactivity for the enzyme forming a collarette around the nucleus (Abu-Alfa et al, 1997).
References
•Aaltonen M, Lipponen P, Kosma VM et al 1995. Prognostic value of cathepsin-D expression in female breast cancer. Anticancer Research 15: 1033-1037.
•Abu-Alfa AK, Kuan SF, West AB, Reyes-Mugica M 1997. Cathepsin D in intestinal ganglion cells. A potential aid to diagnosis in suspected Hirschsprung's disease. American Journal of Surgical Pathology 21: 201-205.
•Allgayer H, Babic R, Grutzner KU et al 1997. An immunohistochemical assessment of cathepsin D in gastric carcinoma: its impact on clinical prognosis. Cancer 80: 179-187.
•Charpin C, Garcia S, Bouvier C et al 1997. Cathepsin D detected by automated and quantative immunohistochemistry in breast carcinomas: correlation with overall and disease free survival. Journal of Clinical Pathology 50: 586-590.
•Dickinson AJ, Fox SB, Newcomb PV et al 1995. An immunohistochemical and prognostic evaluation of cathepsin D expression in 105 bladder carcinomas. Journal of Urology 154: 237-241.
•Duffy MJ 1992. The role of proteolytic enzymes in cancer invasion and metastasis. Clinical and Experimental Metastasis 10: 145-155.
•Higashiyama M, Doi O, Kodama K et al 1997. Influence of cathepsin D expression in lung adenocarcinoma on prognosis: possible importance of its expression in tumor cells and stromal cells, and its intracellular polarization in tumor cells. Journal of Surgical Oncology 65: 10-19.
•Holm R, Hoie J, Kaalhus O, Nesland JM 1995. Immunohistochemical detection of nm23/NDP kinase and cathepsin D in medullary carcinomas of the thyroid gland. Virchows Archives 427: 289-294.
•Isola J, Weitz S, Visakorpi T, et al 1993. Cathepsin D expression detected by immunohistochemistry has independent prognostic value in node-negative breast cancer. Journal of Clinical Oncology 11: 36-43.
•Joensuu H, Toikkanen S, Isola J 1995. Stromal cell cathepsin D expression and long-term survival in breast cancer. British Journal of Cancer 71: 155-159.
•Kristensen GB, Holm R, Abeler VM, Trope CG 1996. Evaluation of the prognostic significance of cathepsin D, epidermal growth factor receptor, and c-erB-2 in early cervical squamous cell carcinoma. An immunohistochemical study. Cancer 78: 433-440.
•Leto G, Gebbia N, Rausa L, Tumminello FM 1992. Cathepsin D in the malignant progression of neoplastic diseases (review). Anticancer Research 12: 235-240.
•Losch A, Kohlberger P, Gitsch G et al 1996. Lysosomal protease cathepsin D is a prognostic marker in endometrial cancer. British Journal of Cancer 73: 1525-1528.
•O'Donoghue AE, Poller DN, Bell JA et al 1995. Cathepsin D in primary breast carcinoma: adverse prognosis is associated with expression of cathepsin D in stromal cells. Breast Cancer Research and Treatment 33: 137-145. prognosis is associated with expression of cathepsin D in stromal cells. Breast Cancer Research and Treatment 33: 137-145.
•Razumovic JJ, Stojkovic RR, Petrovecki M, Gamulin S 1997. Correlation of two methods for determination of cathepsin D in breast carcinoma (immunohistochemistry and ELIZA in cytosol). Breast Cancer Research and Treatment 43: 117-122.
•Schwartz MK 1995. Tissue cathepsins as tumor markers. Clinical Chimia Acta 237: 67-78.
•SlomanA, D'Amico F, Yousem SA 1996. Immunohistochemical markers of prolonged survival in small cell carcinoma of the lung. An immunohistochemical study. Archives of Pathology and Laboratory Medicine 120: 465-472.
•Theodoropoulos GE, Panoussopoulos D, Lazaris AC, Golematis BC 1997. Evaluation of cathepsin D immunostaining in colorectal adenocarcinoma. Journal of Surgical Oncology 5: 242-248.
Bibliografía
Manual of diagnostic antibodies for immunohistology / Anthony S.-Y. Leong, Kumarasen Cooper, F. Joel W.-M. Leong.
