16
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Glomeruloid microvascular proliferation is associated with lack of response to chemotherapy in breast cancer

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background:

          Glomeruloid microvascular proliferation (GMP), a novel histology-based angiogenesis marker, has been associated with decreased survival in several human cancers.

          Methods:

          In this study, we evaluated the ability of GMP to predict clinical response to neoadjuvant chemotherapy in a series of locally advanced breast cancers ( n=112).

          Results:

          Presence of GMP (21% of the cases) was significantly associated with high-grade tumours and TP53 mutations in addition to the basal-like and HER2 subtypes of breast cancer as defined by gene expression data. GMP was correlated to a gene expression signature for tumour hypoxia response. The GMP pattern was also significantly associated with lack of treatment response and progressive disease ( P=0.004).

          Interpretation:

          The findings suggest that GMP might be able to predict the lack of response to neoadjuvant chemotherapy in locally advanced breast cancer. Whether GMP may be an independent predictor compared with other factors including TP53 mutation status and tumour grade needs confirmation in larger studies.

          Related collections

          Most cited references21

          • Record: found
          • Abstract: found
          • Article: not found

          Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up.

          Morphological assessment of the degree of differentiation has been shown in numerous studies to provide useful prognostic information in breast cancer, but until recently histological grading has not been accepted as a routine procedure, mainly because of perceived problems with reproducibility and consistency. In the Nottingham/Tenovus Primary Breast Cancer Study the most commonly used method, described by Bloom & Richardson, has been modified in order to make the criteria more objective. The revised technique involves semiquantitative evaluation of three morphological features--the percentage of tubule formation, the degree of nuclear pleomorphism and an accurate mitotic count using a defined field area. A numerical scoring system is used and the overall grade is derived from a summation of individual scores for the three variables: three grades of differentiation are used. Since 1973, over 2200 patients with primary operable breast cancer have been entered into a study of multiple prognostic factors. Histological grade, assessed in 1831 patients, shows a very strong correlation with prognosis; patients with grade I tumours have a significantly better survival than those with grade II and III tumours (P less than 0.0001). These results demonstrate that this method for histological grading provides important prognostic information and, if the grading protocol is followed consistently, reproducible results can be obtained. Histological grade forms part of the multifactorial Nottingham prognostic index, together with tumour size and lymph node stage, which is used to stratify individual patients for appropriate therapy.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1alpha.

            The switch to an angiogenic phenotype is a fundamental determinant of neoplastic growth and tumor progression. We demonstrate that homozygous deletion of the p53 tumor suppressor gene via homologous recombination in a human cancer cell line promotes the neovascularization and growth of tumor xenografts in nude mice. We find that p53 promotes Mdm2-mediated ubiquitination and proteasomal degradation of the HIF-1alpha subunit of hypoxia-inducible factor 1 (HIF-1), a heterodimeric transcription factor that regulates cellular energy metabolism and angiogenesis in response to oxygen deprivation. Loss of p53 in tumor cells enhances HIF-1alpha levels and augments HIF-1-dependent transcriptional activation of the vascular endothelial growth factor (VEGF) gene in response to hypoxia. Forced expression of HIF-1alpha in p53-expressing tumor cells increases hypoxia-induced VEGF expression and augments neovascularization and growth of tumor xenografts. These results indicate that amplification of normal HIF-1-dependent responses to hypoxia via loss of p53 function contributes to the angiogenic switch during tumorigenesis.
              Bookmark
              • Record: found
              • Abstract: not found
              • Article: not found

              Clinical application of antiangiogenic therapy: microvessel density, what it does and doesn't tell us.

                Bookmark

                Author and article information

                Journal
                Br J Cancer
                British Journal of Cancer
                Nature Publishing Group
                0007-0920
                1532-1827
                28 June 2011
                14 June 2011
                : 105
                : 1
                : 9-12
                Affiliations
                [1 ]simpleThe Gade Institute, Section for Pathology, University of Bergen, Haukeland University Hospital , Bergen N-5021, Norway
                [2 ]simpleDepartment of Oncology, Haukeland University Hospital , Bergen, Norway
                [3 ]simpleDepartment of Genetics, University of Oslo , Oslo, Norway
                [4 ]simpleThe Institute of Genome Sciences and Policy, Department of Molecular Genetics and Microbiology, Duke University School of Medicine , Durham, NC, USA
                [5 ]simpleDepartment of Surgery, Haukeland University Hospital , Bergen, Norway
                [6 ]simpleInstitute of Medicine, Section of Oncology, University of Bergen, and Department of Oncology, Haukeland University Hospital , Bergen, Norway
                Author notes
                Article
                bjc2011203
                10.1038/bjc.2011.203
                3137417
                21673677
                9a5c6e22-8a1e-4bd9-b807-066a9e770b90
                Copyright © 2011 Cancer Research UK
                History
                : 28 January 2011
                : 10 May 2011
                : 12 May 2011
                Categories
                Clinical Study

                Oncology & Radiotherapy
                angiogenesis,neoadjuvant chemotherapy,predictive factor,breast cancer
                Oncology & Radiotherapy
                angiogenesis, neoadjuvant chemotherapy, predictive factor, breast cancer

                Comments

                Comment on this article