The prognostic value of the proliferation marker Phosphohistone H3 (PPH3) in luminal, basal-like and triple negative phenotype invasive lymph node-negative breast cancer
ABSTRACT 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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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.06/2010; 2(2):1040-1065. DOI:10.3390/cancers2021040
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ABSTRACT: Molecular classification of breast cancer (BC) identified diverse subgroups that encompass distinct biological behavior and clinical implications, in particular in relation to prognosis, spread, and incidence of recurrence. Basal-like breast cancers (BLBC) compose up to 15% of BC and are characterized by lack of estrogen receptor (ER), progesterone receptor (PR), and HER-2 amplification with expression of basal cytokeratins 5/6, 14, 17, epidermal growth factor receptor (EGFR), and/or c-KIT. There is an overlap in definition between triple-negative BC and BLBC due to the triple-negative profile of BLBC. Also, most BRCA1-associated BCs are BLBC, triple negative, and express basal cytokeratins (5/6, 14, 17) and EGFR. There is a link between sporadic BLBC (occurring in women without germline BRCA1 mutations) with dysfunction of the BRCA1 pathway. Despite the molecular and clinical similarities, these subtypes respond differently to neoadjuvant therapy. BLBCs are associated with an aggressive phenotype, high histological grade, poor clinical behavior, and high rates of recurrences and/or metastasis. Their molecular features render these tumors especially refractory to anti-hormonal-based therapies and the overall prognosis of this subset remains poor. In this article, the molecular profile, genomic, and epigenetic characteristics as well as BRCA1 pathway dysfunction, clinicopathological behavior, and therapeutic options in BLBC are presented, with emphasis on the discordant findings in current literature.Breast Cancer Research and Treatment 01/2012; 134(1):21-30. DOI:10.1007/s10549-011-1934-z · 4.20 Impact Factor
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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.PLoS ONE 02/2012; 7(2):e31188. DOI:10.1371/journal.pone.0031188 · 3.53 Impact Factor