title: Nm23H1 and p53 proteins are differentially correlated to metastasis in breast carcinoma.
abstract: The prognostic significance of nm23H1 and p53 proteins as predictors of nodal involvement and distant recurrence was evaluated in 63 cancer and 47 benign lesions of the breast. Assessment was carried out by immunohistochemical staining using nm23H1 and p53 antibodies. Results show no relation of nm23H1 either to the malignant nature when compared to benign lesions or to the nodal status. P53 protein, on the other hand, showed significantly increased expression in malignant lesions (p=0.001) and correlated well with nodal positivity (p=0.03). A follow-up study of 5 years showed that among the cases showing recurrence, those with positive mn23H1 showed a shorter distant recurrence free survival (DRFS, p=0.01), while p53 expression had no effect. This result did not agree with the previous reports showing nm23H1 as an antimetastatic gene. This is the first report of positive correlation between nm231-11 and distant recurrence in breast cancers, though such a correlation was reported earlier in certain other cancers. Since nm23H1 is an NDP kinase, having more involvement in signal transduction of cell proliferation, it is not difficult to comprehend such a role for nm23H1 during recurrence. Combining the expression of both proteins, lesions positive for both p53 and nm23H1 had significantly reduced distant recurrence free survival (DRFS), when compared to those negative for both proteins (p=0.0006). It can be concluded that nni23H1 alteration has a potential in predicting DRFS, while p53 alteration has the potential to predict lymph node involvement.
authors.affiliation: Division of Cancer Research, Regional Cancer Centre, Trivandrum, Kerala, India. rcctvm@md2.vsnl.net.in
authors.forename: P
authors.initials: P
authors.lastname: Srinivas
authors.forename: M
authors.initials: M
authors.lastname: Madhavan
authors.forename: I
authors.initials: I
authors.lastname: Ahamed
authors.forename: E
authors.initials: E
authors.lastname: Abraham
authors.forename: N R
authors.initials: NR
authors.lastname: Vijayalakshmy
authors.forename: P
authors.initials: P
authors.lastname: Balaram
mesh_terms: D001943:Breast Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D002277:Carcinoma / Q000175:diagnosis* / Q000401:mortality / Q000556:secondary; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D020559:Monomeric GTP-Binding Proteins / Q000032:analysis* / Q000276:immunology / Q000378:metabolism; D054778:NM23 Nucleoside Diphosphate Kinases; D009362:Neoplasm Metastasis; D009701:Nucleoside-Diphosphate Kinase; D011379:Prognosis; D012008:Recurrence; D016019:Survival Analysis; D014157:Transcription Factors / Q000032:analysis* / Q000276:immunology / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000276:immunology / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000378:metabolism
chemical_list: D054778:NM23 Nucleoside Diphosphate Kinases; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins