Sources/Clones
Accurate (NM301), Accurate/Novocastra (37.6), Dako (polyclonal), Novocastra (nm23-301, polyclonal), Oncogene (NM301, polyclonal) and Pharmingen (NM301).
Fixation/Preparation
Some of the available antibodies are immunoreactive in fixed, paraffin-embedded sections. HIER is required.
Background
The nm23 gene family was originally identified in a murine melanoma cell line and nm23 H1 was found to be transcribed at a ten-fold higher rate in cells of lower metastatic potential. Two highly homologous human genes have subsequently been identified nmE1 and nmE2 located on chromosomes 17q and coding for the 18.5 and 17 kD proteins nm23 H1 and nm23 H2 respectively. nm23 is mainly cytoplasmic, but nuclear and membrane localization has also been seen (Urano et al, 1993).
Applications
The nm23 gene product was initially believed to play a role in suppressing tumor metastasis. This may be too simplistic a view, with both metastasis suppression and disease progression being linked to elevated gene expression in different tumors. Until its precise roles are elucidated, its value as a prognostic indicator is limited.
Isotype-specific studies on breast neoplasms have indicated that it is nm23 H1 and not nm23 H2 that correlates with metastases (Royds et al, 1993). Somatic allelic deletions of nm23 H1 have been reported in some human neoplasms such as breast, kidney, colon and lung cancer, in some cases associated with an increased incidence of metastases (Leone et al, 1991). The loss of nm23 function appears to correlate with phenotypic markers of metastatic potential in some human tumors.
However, there is no strong evidence of direct involvement of the nm23 in metastasis and a bystander effect rather than a causative role for nm23 cannot be ruled out, the reduced nm23 level being a reflection of a more dedifferentiated state of the tumor. nm23 expression correlates inversely with metastatic potential in in vitro and experimental animal systems, with transfection of the nm23 gene into melanoma K1735 cells resulting in a reduction of tumor metastases.
Preliminary studies in esophageal carcinoma (Patel et al 1997) indicate that failure to express p53 and nm23 may be related to an unfavorable prognosis in patients with advanced esophageal carcinoma. Similarly, there is reduced staining of nm23 H1 in laryngeal squamous cell carcinoma compared with laryngeal polyps (Lee et al, 1996b). In contrast, progression of ovarian carcinoma is accompanied by overexpression of nm23 protein (Harlozinska et al, 1996; Srivatsa et al, 1996). While some studies suggest that overexpression of nm23 H1 is an early event in the development of prostatic adenocarcinoma (Igawa et al, 1994; Myers et al, 1996), others show elevated levels of nm23 H1 and H2 in benign prostatic hyperplasia and postulate a role in the suppression of malignancy (Konishi et al, 1993).
In pituitary adenoma, strong expression of nm23 H2 is associated with non-invasive adenomas and may restrain tumor aggression (Takino et al, 1995). Expression in uveal melanoma appears to be inversely proportional to the depth of scleral invasion (Greco et al, 1997) but in melanoma of the skin, there are conflicting studies. Lee et al (1996a) found reduced nm23 H1 immunohistological expression to be associated with melanomas that have high metastatic potential and poorer prognosis. Kanitakis et al (1997) found nm23 to not have a direct correlation with metastatic potential. In transitional cell carcinoma of the bladder (Shiina et al, 1996) and FIGO stage IB cervical carcinoma (Kristensen et al, 1996), nm23 protein immunoreactivity is not an independent prognostic factor. Staining for nm23 has little value in testicular seminoma, where expression of both the nm23 H1 and nm23 H2 proteins was found not to be associated with metastatic or invasive status of the tumor (Hori et al, 1997).
Comments
Polyclonal antiserum to nm23 produces strong cytoplasmic staining after HIER.
References
•Greco IM, Calvisi G, Ventura L, Cerrito F 1997. An immunohistochemical analysis of nm23 gene product expression in uveal melanoma. Melanoma Research; 7: 231-236.
•Harlozinska A, Bar JK, Gerber J 1996. nm23 expression in tissue sections and tumor effusion cells of ovarian neoplasms. International Journal of Cancer; 69: 415-419
•Hori K, Uematsu K, Yaswoshima H et al 1997. Immunohistochemical analysis of the nm23 gene products in testicular seminoma. Pathology International; 47: 288-292.
•Igawa M, Rukstalis DB, Tanabe T, Chodak GW 1994. High levels of nm23 expression are related to cell proliferation in human prostate cancer. Cancer Research; 54: 1313-1318.
•Kanitakis J, Euvrard S, Bourchany D et al 1997. Expression of the nm23 metastasis-suppressor gene product in skin tumors. Journal of Cutaneous Pathology; 24: 151-156.
•Konishi N, Nakaoka S, Tsuzuki T et al 1993. Expression of nm23-H1 and nm23-H2 proteins in prostate carcinoma. Japanese Journal of Cancer Research; 84: 1050-1054.
•Kristensen GB, Holm R, Abeler VM, Trope CG 1996. Evaluation of the prognostic signifcance of nm23/NDP kinase protein expression in cervical carcinoma: an immunohistochemical study. Gynecological Oncology; 61: 378-383.
•Lee CS, Pirdas A, Lee MW 1996a. Immunohistochemical demonstration of the nm23-H1 gene product in human malignant melanoma and Spitz nevi. Pathology; 28: 220-224.
•Lee CS, Redshaw A, Boag G 1996b. nm23-H1 protein immunoreactivity in laryngeal carcinoma. Cancer; 77:2246-2250.
•Leone A, McBride OW, Weston A 1991. Somatic allelic deletion of nm23 in human cancer. Cancer Research; 51: 2490-2493.
•Myers RB, Srivastava S, Oelschlager DK et al 1996. Expression of nm23-H1 in prostatic intraepithelial neoplasia and adenocarcinoma. Human Pathology; 27: 1021-1024.
•Patel DD, Bhatavdekar JM, Chikhlikar PR et al 1997. Clinical significance of p53, nm23, and bc1-2 in T3-4N1M0 oesophageal carcinoma: an immunohistochemical approach. Journal of Surgical Oncology; 65: 111-116.
•Royds JA, Stephenson TJ, Rees RC 1993. nm23 protein expression in ductal in situ and invasive human breast carcinoma. Journal of the National Cancer Institutes; 85: 727-731.
•Shiina H, Igawa M, Nagami H et al 1996. Immunohistochemical analysis of proliferating cell nuclear antigen, p53 protein and nm23 protein, and nuclear DNA content in transitional cell carcinoma of the bladder. Cancer; 78:1762 1774. antigen, p53 protein and nm23 protein, and nuclear DNA content in transitional cell carcinoma of the bladder. Cancer; 78:1762 1774.
•Srivatsa PJ, Cliby WA, Keeney GL et al 1996. Elevated nm23 protein expression is correlated with diminished progression-free survival in patients with epithelial ovarian carcinoma. Gynecological Oncology; 60: 363-372.
•Takino H, Herman V, Weiss M, Melmed S 1995. Purine-binding factor (nm23) gene expression in pituitary tumors: marker of adenoma invasiveness. Journal of Clinical Endocrinology and Metabolism; 80: 1733-1738.
•Urano T, Furukawa K, Shiku H 1993. Expression of nm23/NDP kinase proteins on the cell surface. Oncogene; 8: 1371-1376.
Bibliografia
Manual of diagnostic antibodies for immunohistology / Anthony S.-Y. Leong, Kumarasen Cooper, F. Joel W.-M. Leong.
Accurate (NM301), Accurate/Novocastra (37.6), Dako (polyclonal), Novocastra (nm23-301, polyclonal), Oncogene (NM301, polyclonal) and Pharmingen (NM301).
Fixation/Preparation
Some of the available antibodies are immunoreactive in fixed, paraffin-embedded sections. HIER is required.
Background
The nm23 gene family was originally identified in a murine melanoma cell line and nm23 H1 was found to be transcribed at a ten-fold higher rate in cells of lower metastatic potential. Two highly homologous human genes have subsequently been identified nmE1 and nmE2 located on chromosomes 17q and coding for the 18.5 and 17 kD proteins nm23 H1 and nm23 H2 respectively. nm23 is mainly cytoplasmic, but nuclear and membrane localization has also been seen (Urano et al, 1993).
Applications
The nm23 gene product was initially believed to play a role in suppressing tumor metastasis. This may be too simplistic a view, with both metastasis suppression and disease progression being linked to elevated gene expression in different tumors. Until its precise roles are elucidated, its value as a prognostic indicator is limited.
Isotype-specific studies on breast neoplasms have indicated that it is nm23 H1 and not nm23 H2 that correlates with metastases (Royds et al, 1993). Somatic allelic deletions of nm23 H1 have been reported in some human neoplasms such as breast, kidney, colon and lung cancer, in some cases associated with an increased incidence of metastases (Leone et al, 1991). The loss of nm23 function appears to correlate with phenotypic markers of metastatic potential in some human tumors.
However, there is no strong evidence of direct involvement of the nm23 in metastasis and a bystander effect rather than a causative role for nm23 cannot be ruled out, the reduced nm23 level being a reflection of a more dedifferentiated state of the tumor. nm23 expression correlates inversely with metastatic potential in in vitro and experimental animal systems, with transfection of the nm23 gene into melanoma K1735 cells resulting in a reduction of tumor metastases.
Preliminary studies in esophageal carcinoma (Patel et al 1997) indicate that failure to express p53 and nm23 may be related to an unfavorable prognosis in patients with advanced esophageal carcinoma. Similarly, there is reduced staining of nm23 H1 in laryngeal squamous cell carcinoma compared with laryngeal polyps (Lee et al, 1996b). In contrast, progression of ovarian carcinoma is accompanied by overexpression of nm23 protein (Harlozinska et al, 1996; Srivatsa et al, 1996). While some studies suggest that overexpression of nm23 H1 is an early event in the development of prostatic adenocarcinoma (Igawa et al, 1994; Myers et al, 1996), others show elevated levels of nm23 H1 and H2 in benign prostatic hyperplasia and postulate a role in the suppression of malignancy (Konishi et al, 1993).
In pituitary adenoma, strong expression of nm23 H2 is associated with non-invasive adenomas and may restrain tumor aggression (Takino et al, 1995). Expression in uveal melanoma appears to be inversely proportional to the depth of scleral invasion (Greco et al, 1997) but in melanoma of the skin, there are conflicting studies. Lee et al (1996a) found reduced nm23 H1 immunohistological expression to be associated with melanomas that have high metastatic potential and poorer prognosis. Kanitakis et al (1997) found nm23 to not have a direct correlation with metastatic potential. In transitional cell carcinoma of the bladder (Shiina et al, 1996) and FIGO stage IB cervical carcinoma (Kristensen et al, 1996), nm23 protein immunoreactivity is not an independent prognostic factor. Staining for nm23 has little value in testicular seminoma, where expression of both the nm23 H1 and nm23 H2 proteins was found not to be associated with metastatic or invasive status of the tumor (Hori et al, 1997).
Comments
Polyclonal antiserum to nm23 produces strong cytoplasmic staining after HIER.
References
•Greco IM, Calvisi G, Ventura L, Cerrito F 1997. An immunohistochemical analysis of nm23 gene product expression in uveal melanoma. Melanoma Research; 7: 231-236.
•Harlozinska A, Bar JK, Gerber J 1996. nm23 expression in tissue sections and tumor effusion cells of ovarian neoplasms. International Journal of Cancer; 69: 415-419
•Hori K, Uematsu K, Yaswoshima H et al 1997. Immunohistochemical analysis of the nm23 gene products in testicular seminoma. Pathology International; 47: 288-292.
•Igawa M, Rukstalis DB, Tanabe T, Chodak GW 1994. High levels of nm23 expression are related to cell proliferation in human prostate cancer. Cancer Research; 54: 1313-1318.
•Kanitakis J, Euvrard S, Bourchany D et al 1997. Expression of the nm23 metastasis-suppressor gene product in skin tumors. Journal of Cutaneous Pathology; 24: 151-156.
•Konishi N, Nakaoka S, Tsuzuki T et al 1993. Expression of nm23-H1 and nm23-H2 proteins in prostate carcinoma. Japanese Journal of Cancer Research; 84: 1050-1054.
•Kristensen GB, Holm R, Abeler VM, Trope CG 1996. Evaluation of the prognostic signifcance of nm23/NDP kinase protein expression in cervical carcinoma: an immunohistochemical study. Gynecological Oncology; 61: 378-383.
•Lee CS, Pirdas A, Lee MW 1996a. Immunohistochemical demonstration of the nm23-H1 gene product in human malignant melanoma and Spitz nevi. Pathology; 28: 220-224.
•Lee CS, Redshaw A, Boag G 1996b. nm23-H1 protein immunoreactivity in laryngeal carcinoma. Cancer; 77:2246-2250.
•Leone A, McBride OW, Weston A 1991. Somatic allelic deletion of nm23 in human cancer. Cancer Research; 51: 2490-2493.
•Myers RB, Srivastava S, Oelschlager DK et al 1996. Expression of nm23-H1 in prostatic intraepithelial neoplasia and adenocarcinoma. Human Pathology; 27: 1021-1024.
•Patel DD, Bhatavdekar JM, Chikhlikar PR et al 1997. Clinical significance of p53, nm23, and bc1-2 in T3-4N1M0 oesophageal carcinoma: an immunohistochemical approach. Journal of Surgical Oncology; 65: 111-116.
•Royds JA, Stephenson TJ, Rees RC 1993. nm23 protein expression in ductal in situ and invasive human breast carcinoma. Journal of the National Cancer Institutes; 85: 727-731.
•Shiina H, Igawa M, Nagami H et al 1996. Immunohistochemical analysis of proliferating cell nuclear antigen, p53 protein and nm23 protein, and nuclear DNA content in transitional cell carcinoma of the bladder. Cancer; 78:1762 1774. antigen, p53 protein and nm23 protein, and nuclear DNA content in transitional cell carcinoma of the bladder. Cancer; 78:1762 1774.
•Srivatsa PJ, Cliby WA, Keeney GL et al 1996. Elevated nm23 protein expression is correlated with diminished progression-free survival in patients with epithelial ovarian carcinoma. Gynecological Oncology; 60: 363-372.
•Takino H, Herman V, Weiss M, Melmed S 1995. Purine-binding factor (nm23) gene expression in pituitary tumors: marker of adenoma invasiveness. Journal of Clinical Endocrinology and Metabolism; 80: 1733-1738.
•Urano T, Furukawa K, Shiku H 1993. Expression of nm23/NDP kinase proteins on the cell surface. Oncogene; 8: 1371-1376.
Bibliografia
Manual of diagnostic antibodies for immunohistology / Anthony S.-Y. Leong, Kumarasen Cooper, F. Joel W.-M. Leong.
