Sources/Clones
Biogenex (GCDFP-15) and Signet (GCDFP-15)
Fixation/Preparation
The antigen is fixation stable and can be detected in paraffin-embedded sections as well as fresh-frozen sections and cell preparations. HIER enhances immunostaining and proteolytic digestion is unnecessary. Cytologic preparations should be fixed in 10% formalin or Bouin's solution. Alcohol-fixed preparations are not immunoreactive.
Background
Gross cystic disease fluid protein-15 (GCDFP-15) is one of four major component proteins found in the cystic fluid obtained from patients with fibrocystic changes of the breast. GCDFP-15 is a marker of apocrine glandular differentiation in both benign and malignant mammary epithelium (Haagensen et al, 1990). This protein has widespread distribution in apocrine glands elsewhere in the axillary and perianal tissues, as well as in the sublingual and submaxillary salivary glands. The GCDFP-15 protein is a 15 kD glycoprotein shown to be prolactin inducible, the GCDFP-15 gene having been recently cloned (Myal et al, 1991). Ultrastructurally, the GCDFP-15 protein has been localized in Golgi vesicles and cytoplasmic granules. The protein is released by exocytosis at the apices of the mammary epithelial cells (Mazoujian et al, 1984).
Applications
Carcinoma of the breast is a treatable disease with a variable prognostic outcome. Its recognition is therefore of great therapeutic importance but in metastatic sites, identification of breast carcinoma can often be difficult. A marker of mammary epithelial differentiation would be of diagnostic importance. GCDFP-15 goes some way towards fulfiling this role and is currently the best marker yet to identify breast cancer metastases. GCDFP-15 was identified by immunostaining in 55-74% of cases of breast carcinoma (Mazoujian et al, 1989; Wick et al, 1989) and has a higher rate of sensitivity and specificity than a-lactalbumin as a marker of both primary and metastatic breast cancer. Besides mammary carcinomas, the major tumor types that expressed GCDFP-15 were salivary glands, sweat glands and prostate (Wick et al, 1989). It is also a marker of apocrine differentiation in the skin (particularly in combination with lysozyme) and can be suitably applied for the separation of cutaneous adnexal tumors (Appendix 1.19). It is worth noting that the expression of GCDFP-15 varies among the histologic subtypes of breast carcinoma, with highest incidence in infiltrating lobular carcinoma with signet ring cell differentiation (90%), compared to 70% in ordinary infiltrating ductal carcinoma and 75% in those subtypes showing apocrine differentiation (Mazoujian et al, 1989). Expression of the GCDFP-15 gene was significantly associated with relapse-free survival and was suggested to represent a marker of prognostic relevance (Pagani et al, 1994).
Antibodies to GCDFP-15 have been used successfully to identify metastases from breast carcinoma in the brain (Perry et al, 1997), ovary (Monteagudo et al, 1991) and other sites (Chaubert & Hurlimann, 1992). Immunodistinction of metastasis from breast cancer and eccrine and apocrine tumors in the skin can be difficult as the latter tumors also express this antigen (Tsubura et al, 1992; Wallace et al, 1995; Wallace & Smoller, 1996). However, as with other metastatic sites, the highest diagnostic yield was obtained when anti-GCDFP-15 was employed together with other antibodies in a diagnostic panel.
GCDFP-15 is also a suitable marker in cytological specimens and the best results are obtained following fixation in 10% formalin or Bouin's solution, alcohol-fixed samples showing no immunoreactivity for this antigen (Fiel et al, 1996).
Comments
The immunoreactivity of monoclonal antibodies and polyclonal antisera to GCDFP-15 appears to be the same (Mazoujian et al, 1988), HIER enhancing immunoreactivity of both antibodies.
References
•Chaubert P, Hurlimann J 1992. Mammary origin of metastases. Immunohistochemical determination. Archives of Pathology and Laboratory Medicine 116: 1181-1188.
•Fiel MI, Cernainu G, Burstein DE, Batheja N 1996. Value of GCDFP-15 (BRST-2) as a specific immunocytochemical marker for breast carcinoma in cytologic specimens. Acta Cytologica 40: 637-641.
•Haagensen DE Jr, Dilley WG, Mazoujian G, Wells SA Jr 1990. Review of GCDFP-15. An apocrine marker protein. Annals of the New York Academy of Sciences 586: 161-173.
•Mazoujian G, Wahol MJ, Haagensen DE Jr 1984. The ultrastructural localization of gross cystic disease fluid protein-15 (GCDFP-15) in breast epithelium. American Journal of Pathology 116: 305-310.
•Mazoujian G, Parish TH, Haagensen DE Jr 1988. Immunoperoxidase localization of GCDFP-15 with mouse monoclonal antibodies versus rabbit antiserum. Journal of Histochemistry and Cytochemistry 36: 377-382.
•Mazoujian G, Bodian C, Haagensen DE Jr, Haagensen CD 1989. Expression of GCDFP-15 in breast carcinomas. Relationship to pathologic and clinical factors. Cancer 63:2156-2161.
•Monteagudo C, Merino MJ, LaPorte N, Neumann RD 1991. Value of gross cystic disease fluid protein-15 in distinguishing metastatic breast carcinomas among poorly differentiated neoplasms involving the ovary. Human Pathology 22: 368-372.
•Myal Y, Robinson DB, Iwasiow B et al 1991. The prolactin-inducible protein (PIP/GCDFP-15) gene: cloning, structure and regulation. Molecular and Cellular Endocrinology 80:165-175.
•Pagani A, Sapino A, Eusebi V et al 1994. (PIP/GCDFP-15) gene expression and apocrine differentiation in carcinomas of the breast. Virchows Archives 425: 459-465.
•Perry A, Parisi JE, Kurtin PJ 1997. Metastatic adenocarcinoma to the brain: an immunohistochemical approach. Human Pathology 28: 938-943.
•Tsubura A, Senzaki H, Sasaki M et al 1992. Immunohistochemical demonstration of breast-derived and/or carcinoma-associated glycoproteins in normal skin appendages and their tumors. Journal of Cutaneous Pathology 19:73-79.
•Wallace ML, Smoller BR 1996. Differential sensitivity of estrogen/progesterone receptors and BRST-2 markers in metastatic ductal and lobular breast carcinoma to the skin. American Journal of Dermatopathology 18:241-247.
•Wallace ML, Longacre TA, Smoller BR 1995. Estrogen and progesterone receptors and antigross cystic disease fluid protein-15 (BRST-2) fail to distinguish metastatic breast carcinoma from eccrine neoplasms. Modern Pathology 8:897-901.
•Wick MR, Lillemoe TJ, Copland GT et al 1989. Gross cystic disease fluid protein-15 as a marker for breast cancer: immunohistochemical analysis of 690 human neoplasms and comparison with alphalactalbumin. Human Pathology 20: 281-287.
Bibliografía
Manual of diagnostic antibodies for immunohistology / Anthony S.-Y. Leong, Kumarasen Cooper, F. Joel W.-M. Leong.
Biogenex (GCDFP-15) and Signet (GCDFP-15)
Fixation/Preparation
The antigen is fixation stable and can be detected in paraffin-embedded sections as well as fresh-frozen sections and cell preparations. HIER enhances immunostaining and proteolytic digestion is unnecessary. Cytologic preparations should be fixed in 10% formalin or Bouin's solution. Alcohol-fixed preparations are not immunoreactive.
Background
Gross cystic disease fluid protein-15 (GCDFP-15) is one of four major component proteins found in the cystic fluid obtained from patients with fibrocystic changes of the breast. GCDFP-15 is a marker of apocrine glandular differentiation in both benign and malignant mammary epithelium (Haagensen et al, 1990). This protein has widespread distribution in apocrine glands elsewhere in the axillary and perianal tissues, as well as in the sublingual and submaxillary salivary glands. The GCDFP-15 protein is a 15 kD glycoprotein shown to be prolactin inducible, the GCDFP-15 gene having been recently cloned (Myal et al, 1991). Ultrastructurally, the GCDFP-15 protein has been localized in Golgi vesicles and cytoplasmic granules. The protein is released by exocytosis at the apices of the mammary epithelial cells (Mazoujian et al, 1984).
Applications
Carcinoma of the breast is a treatable disease with a variable prognostic outcome. Its recognition is therefore of great therapeutic importance but in metastatic sites, identification of breast carcinoma can often be difficult. A marker of mammary epithelial differentiation would be of diagnostic importance. GCDFP-15 goes some way towards fulfiling this role and is currently the best marker yet to identify breast cancer metastases. GCDFP-15 was identified by immunostaining in 55-74% of cases of breast carcinoma (Mazoujian et al, 1989; Wick et al, 1989) and has a higher rate of sensitivity and specificity than a-lactalbumin as a marker of both primary and metastatic breast cancer. Besides mammary carcinomas, the major tumor types that expressed GCDFP-15 were salivary glands, sweat glands and prostate (Wick et al, 1989). It is also a marker of apocrine differentiation in the skin (particularly in combination with lysozyme) and can be suitably applied for the separation of cutaneous adnexal tumors (Appendix 1.19). It is worth noting that the expression of GCDFP-15 varies among the histologic subtypes of breast carcinoma, with highest incidence in infiltrating lobular carcinoma with signet ring cell differentiation (90%), compared to 70% in ordinary infiltrating ductal carcinoma and 75% in those subtypes showing apocrine differentiation (Mazoujian et al, 1989). Expression of the GCDFP-15 gene was significantly associated with relapse-free survival and was suggested to represent a marker of prognostic relevance (Pagani et al, 1994).
Antibodies to GCDFP-15 have been used successfully to identify metastases from breast carcinoma in the brain (Perry et al, 1997), ovary (Monteagudo et al, 1991) and other sites (Chaubert & Hurlimann, 1992). Immunodistinction of metastasis from breast cancer and eccrine and apocrine tumors in the skin can be difficult as the latter tumors also express this antigen (Tsubura et al, 1992; Wallace et al, 1995; Wallace & Smoller, 1996). However, as with other metastatic sites, the highest diagnostic yield was obtained when anti-GCDFP-15 was employed together with other antibodies in a diagnostic panel.
GCDFP-15 is also a suitable marker in cytological specimens and the best results are obtained following fixation in 10% formalin or Bouin's solution, alcohol-fixed samples showing no immunoreactivity for this antigen (Fiel et al, 1996).
Comments
The immunoreactivity of monoclonal antibodies and polyclonal antisera to GCDFP-15 appears to be the same (Mazoujian et al, 1988), HIER enhancing immunoreactivity of both antibodies.
References
•Chaubert P, Hurlimann J 1992. Mammary origin of metastases. Immunohistochemical determination. Archives of Pathology and Laboratory Medicine 116: 1181-1188.
•Fiel MI, Cernainu G, Burstein DE, Batheja N 1996. Value of GCDFP-15 (BRST-2) as a specific immunocytochemical marker for breast carcinoma in cytologic specimens. Acta Cytologica 40: 637-641.
•Haagensen DE Jr, Dilley WG, Mazoujian G, Wells SA Jr 1990. Review of GCDFP-15. An apocrine marker protein. Annals of the New York Academy of Sciences 586: 161-173.
•Mazoujian G, Wahol MJ, Haagensen DE Jr 1984. The ultrastructural localization of gross cystic disease fluid protein-15 (GCDFP-15) in breast epithelium. American Journal of Pathology 116: 305-310.
•Mazoujian G, Parish TH, Haagensen DE Jr 1988. Immunoperoxidase localization of GCDFP-15 with mouse monoclonal antibodies versus rabbit antiserum. Journal of Histochemistry and Cytochemistry 36: 377-382.
•Mazoujian G, Bodian C, Haagensen DE Jr, Haagensen CD 1989. Expression of GCDFP-15 in breast carcinomas. Relationship to pathologic and clinical factors. Cancer 63:2156-2161.
•Monteagudo C, Merino MJ, LaPorte N, Neumann RD 1991. Value of gross cystic disease fluid protein-15 in distinguishing metastatic breast carcinomas among poorly differentiated neoplasms involving the ovary. Human Pathology 22: 368-372.
•Myal Y, Robinson DB, Iwasiow B et al 1991. The prolactin-inducible protein (PIP/GCDFP-15) gene: cloning, structure and regulation. Molecular and Cellular Endocrinology 80:165-175.
•Pagani A, Sapino A, Eusebi V et al 1994. (PIP/GCDFP-15) gene expression and apocrine differentiation in carcinomas of the breast. Virchows Archives 425: 459-465.
•Perry A, Parisi JE, Kurtin PJ 1997. Metastatic adenocarcinoma to the brain: an immunohistochemical approach. Human Pathology 28: 938-943.
•Tsubura A, Senzaki H, Sasaki M et al 1992. Immunohistochemical demonstration of breast-derived and/or carcinoma-associated glycoproteins in normal skin appendages and their tumors. Journal of Cutaneous Pathology 19:73-79.
•Wallace ML, Smoller BR 1996. Differential sensitivity of estrogen/progesterone receptors and BRST-2 markers in metastatic ductal and lobular breast carcinoma to the skin. American Journal of Dermatopathology 18:241-247.
•Wallace ML, Longacre TA, Smoller BR 1995. Estrogen and progesterone receptors and antigross cystic disease fluid protein-15 (BRST-2) fail to distinguish metastatic breast carcinoma from eccrine neoplasms. Modern Pathology 8:897-901.
•Wick MR, Lillemoe TJ, Copland GT et al 1989. Gross cystic disease fluid protein-15 as a marker for breast cancer: immunohistochemical analysis of 690 human neoplasms and comparison with alphalactalbumin. Human Pathology 20: 281-287.
Bibliografía
Manual of diagnostic antibodies for immunohistology / Anthony S.-Y. Leong, Kumarasen Cooper, F. Joel W.-M. Leong.
