Skaland I, Janssen EA, Gudlaugsson E, et al. The prognostic value of the proliferation marker phosphohistone H3 (PPH3) in luminal, basal-like and triple negative phenotype invasive lymph node-negative breast cancer

Department of Pathology, Stavanger University Hospital, Stavanger, Norway.
Cellular oncology: the official journal of the International Society for Cellular Oncology (Impact Factor: 4.17). 01/2009; 31(4):261-71. DOI: 10.3233/CLO-2009-0464
Source: PubMed


Prognostic comparison of phosphohistone-H3 (PPH3) with Cytokeratin 5/6 and/or 14 positive (=basal-CK), triple (ER, PR, HER2)-negative (=TNP) and basal-like (=TNP and basal-CK positive) phenotype in invasive breast cancers.
Classical variables, PPH3, ER, PR, basal-CK and HER2 in 240 T1-2N0M0 patients under 71 years.
TNP and basal-like cancers had higher PPH3 expression than the other cancers (mean 48 versus 11, P<0.001). Fifteen percent of the patients in the whole group, but 32-38% of TNP and basal-like cancers recurred. With multivariate analysis, PPH3<13 (n=156) versus >or=13 (n=84=35% of all cases) was the strongest and only prognosticator (10-year survival 96% and 64%, P<or=0.001, Hazard ratio=9.0).
PPH3 is the strongest prognosticators in luminal, Triple negative and basal-like T1-2N0M0 invasive breast cancers.

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    • "The percentage of CK5/6 positive tumour cells in each cancer was scored using a continuous scale of 0–100%. In the final analysis all tumours with any CK5/6 staining in tumour cells were grouped as being positive as described before [22]. ERα was scored positive if ≥1% of tumours cells showed nuclear staining and all others were scored negative. "
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    ABSTRACT: Although lymph node negative (LN-) breast cancer patients have a good 10-years survival (∼85%), most of them still receive adjuvant therapy, while only some benefit from this. More accurate prognostication of LN- breast cancer patient may reduce over- and under-treatment. Until now proliferation is the strongest prognostic factor for LN- breast cancer patients. The small molecule microRNA (miRNA) has opened a new window for prognostic markers, therapeutic targets and/or therapeutic components. Previously it has been shown that miR-18a/b, miR-25, miR-29c and miR-106b correlate to high proliferation.
    Full-text · Article · Nov 2012 · PLoS ONE
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    • "Phospho-histone H3 has been similarly employed to evaluate tumor grade and aggressiveness [32], [33]. Phospho-histone H3 is a prognostic proliferation marker in triple negative invasive lymph node-negative breast cancer [50]. "
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    ABSTRACT: Lysyl oxidase propeptide (LOX-PP) ectopic overexpression inhibits the growth of cancer xenografts. Here the ability and mode of action of purified recombinant LOX-PP (rLOX-PP) protein to inhibit the growth of pre-existing xenografts was determined. Experimental approaches employed were direct intratumoral injection (i.t.) of rLOX-PP protein into murine breast cancer NF639 xenografts, and application of a slow release formulation of rLOX-PP implanted adjacent to tumors in NCR nu/nu mice (n = 10). Tumors were monitored for growth, and after sacrifice were subjected to immunohistochemical and Western blot analyses for several markers of proliferation, apoptosis, and for rLOX-PP itself. Direct i.t. injection of rLOX-PP significantly reduced tumor volume on days 20, 22 and 25 and tumor weight at harvest on day 25 by 30% compared to control. Implantation of beads preloaded with 35 micrograms rLOX-PP (n = 10) in vivo reduced tumor volume and weight at sacrifice when compared to empty beads (p<0.05). A 30% reduction of tumor volume on days 22 and 25 (p<0.05) and final tumor weight on day 25 (p<0.05) were observed with a reduced tumor growth rate of 60% after implantation. rLOX-PP significantly reduced the expression of proliferation markers and Erk1/2 MAP kinase activation, while prominent increases in apoptosis markers were observed. rLOX-PP was detected by immunohistochemistry in harvested rLOX-PP tumors, but not in controls. Data provide pre-clinical findings that support proof of principle for the therapeutic anti-cancer potential of rLOX-PP protein formulations.
    Full-text · Article · Feb 2012 · PLoS ONE
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    ABSTRACT: Initially recognized through microarray-based gene expression profiling, basal-like breast cancer, for which we lack effective targeted therapies, is an aggressive form of carcinoma with a predilection for younger women. With some success, immunohistochemical studies have attempted to reproduce the expression profile classification of breast cancer through identification of subtype-specific biomarkers. This review aims to present an in depth summary and analysis of the current status of basal-like breast cancer biomarker research. While a number of biomarkers show promise for future clinical application, the next logical step is a comprehensive investigation of all biomarkers against a gene expression profile gold standard for breast cancer subtype assignment.
    Full-text · Article · Jun 2010 · Cancers
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