Combined proliferation and apoptosis index provides better risk stratification in breast cancer

Breast cancer (BC) risk stratification is critical for predicting behaviour and guiding management decision‐making. Despite the well‐established prognostic value of cellular proliferation in BC, the interplay between proliferation and apoptosis remains to be defined. In this study, we hypothesised that the combined proliferation and apoptosis indices can provide a more accurate in‐vivo growth rate measure and a precise prognostic predictor.

[1]  G. Ball,et al.  Defining the area of mitoses counting in invasive breast cancer using whole slide image , 2021, Modern Pathology.

[2]  E. Rakha,et al.  Assessment of mitotic activity in breast cancer: revisited in the digital pathology era , 2021, Journal of Clinical Pathology.

[3]  V. Sopik International variation in breast cancer incidence and mortality in young women , 2020, Breast Cancer Research and Treatment.

[4]  Ronnachai Jaroensri,et al.  Artificial intelligence in digital breast pathology: Techniques and applications , 2019, Breast.

[5]  A. Dimberg,et al.  Tumor angiogenesis: causes, consequences, challenges and opportunities , 2019, Cellular and Molecular Life Sciences.

[6]  Jing Wang,et al.  WebGestalt 2019: gene set analysis toolkit with revamped UIs and APIs , 2019, Nucleic Acids Res..

[7]  A. Letai,et al.  Regulation of apoptosis in health and disease: the balancing act of BCL-2 family proteins , 2019, Nature Reviews Molecular Cell Biology.

[8]  Melissa A. Troester,et al.  Lifestyle Patterns and Survival Following Breast Cancer in the Carolina Breast Cancer Study , 2019, Epidemiology.

[9]  Lin Lin,et al.  Clinicopathologic features and prognostic implications of MYBL2 protein expression in pancreatic ductal adenocarcinoma. , 2017, Pathology, research and practice.

[10]  B. Zhivotovsky,et al.  Understanding cell cycle and cell death regulation provides novel weapons against human diseases , 2017, Journal of internal medicine.

[11]  N. Waterhouse,et al.  Detecting Cleaved Caspase-3 in Apoptotic Cells by Flow Cytometry. , 2016, Cold Spring Harbor protocols.

[12]  Yang Wang,et al.  Dynamic and modular gene regulatory networks drive the development of gametogenesis , 2016, Briefings Bioinform..

[13]  P. Bolufer,et al.  Study of the S427G polymorphism and of MYBL2 variants in patients with acute myeloid leukemia , 2016, Leukemia & lymphoma.

[14]  Na Zhao,et al.  Next-generation sequencing of colorectal cancers in chinese: identification of a recurrent frame-shift and gain-of-function Indel mutation in the TFDP1 gene. , 2014, Omics : a journal of integrative biology.

[15]  P. Kuppen,et al.  The prognostic value of apoptotic and proliferative markers in breast cancer , 2013, Breast Cancer Research and Treatment.

[16]  Joel H. Saltz,et al.  Research and applications: Cancer Digital Slide Archive: an informatics resource to support integrated in silico analysis of TCGA pathology data , 2013, J. Am. Medical Informatics Assoc..

[17]  D. Hanahan,et al.  Hallmarks of Cancer: The Next Generation , 2011, Cell.

[18]  Z. Szallasi,et al.  An online survival analysis tool to rapidly assess the effect of 22,277 genes on breast cancer prognosis using microarray data of 1,809 patients , 2010, Breast Cancer Research and Treatment.

[19]  Shu Ichihara,et al.  Breast cancer prognostic classification in the molecular era: the role of histological grade , 2010, Breast Cancer Research.

[20]  Ian O Ellis,et al.  Prognostic significance of Nottingham histologic grade in invasive breast carcinoma. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  T. Cotter,et al.  Morphological assessment of apoptosis. , 2008, Methods.

[22]  Ian O Ellis,et al.  Biologic and clinical characteristics of breast cancer with single hormone receptor positive phenotype. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[23]  J. Baak,et al.  Prognostic value of proliferation in invasive breast cancer: a review , 2004, Journal of Clinical Pathology.

[24]  J. Inazawa,et al.  Association of over-expressed TFDP1 with progression of hepatocellular carcinomas , 2003, Journal of Human Genetics.

[25]  P. Shannon,et al.  Cytoscape: a software environment for integrated models of biomolecular interaction networks. , 2003, Genome research.

[26]  Lajos Pusztai,et al.  Breast cancer biomarkers and molecular medicine , 2003, Expert review of molecular diagnostics.

[27]  J. Jager,et al.  Clinical relevance of apoptotic markers in breast cancer not yet clear , 2002, Apoptosis.

[28]  C. Potten,et al.  Education and debate , 2022 .

[29]  A. Thor,et al.  Measures of cell turnover (proliferation and apoptosis) and their association with survival in breast cancer. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[30]  G. Häcker The morphology of apoptosis , 2000, Cell and Tissue Research.

[31]  J. D. Jong,et al.  Number of apoptotic cells as a prognostic marker in invasive breast cancer , 2000, British Journal of Cancer.

[32]  M. Monden,et al.  Both cell proliferation and apoptosis significantly predict shortened disease-free survival in hepatocellular carcinoma , 1999, British Journal of Cancer.

[33]  P. Brousset,et al.  In vivo patterns of Bcl‐2 family protein expression in breast carcinomas in relation to apoptosis , 1999, The Journal of pathology.

[34]  John Calvin Reed Dysregulation of apoptosis in cancer. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[35]  R. Abe,et al.  Apoptotic index correlates to bcl-2 and p53 protein expression, histological grade and prognosis in invasive breast cancers. , 1998, Anticancer research.

[36]  C. Osborne,et al.  bcl‐2 and apoptosis in lymph node positive breast carcinoma , 1998, Cancer.

[37]  J. Wang,et al.  Cellular responses to DNA damage. , 1998, Current opinion in cell biology.

[38]  M. J. van de Vijver,et al.  Loss of Bcl-2 in invasive breast cancer is associated with high rates of cell death, but also with increased proliferative activity. , 1998, British Journal of Cancer.

[39]  M. Itabashi,et al.  Expression of Bcl‐2 in human breast cancer: Correlation between hormone receptor status, p53 protein accumulation and DNA strand breaks associated with apoptosis , 1997, Pathology international.

[40]  G. Pelosi,et al.  Ki‐67 immunostaining in 322 primary breast cancers: Associations with clinical and pathological variables and prognosis , 1997, International journal of cancer.

[41]  M. Dowsett,et al.  Preoperative chemotherapy induces apoptosis in early breast cancer , 1997, The Lancet.

[42]  C. Kitanaka,et al.  Apoptosis in cancer. , 1996, Human cell.

[43]  P. V. van Diest,et al.  Counting of apoptotic cells: a methodological study in invasive breast cancer , 1996, Clinical molecular pathology.

[44]  M. Heatley,et al.  Association between the apoptotic index and established prognostic parameters in endometrial adenocarcinoma , 1995, Histopathology.

[45]  E. Lam,et al.  Proto-oncogenic properties of the DP family of proteins. , 1995, Oncogene.

[46]  J. Nevins,et al.  Oncogenic capacity of the E2F1 gene. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[47]  P. Lipponen,et al.  Apoptosis in bladder cancer as related to standard prognostic factors and prognosis , 1994, The Journal of pathology.

[48]  D. Livingston,et al.  Binding to DNA and the retinoblastoma gene product promoted by complex formation of different E2F family members. , 1993, Science.

[49]  L. Johnston,et al.  Functional synergy between DP‐1 and E2F‐1 in the cell cycle‐regulating transcription factor DRTF1/E2F. , 1993, The EMBO journal.

[50]  N. L. La Thangue,et al.  A new component of the transcription factor DRTF1/E2F , 1993, Nature.

[51]  S. Pileri,et al.  Correlations between apoptotic and proliferative indices in malignant non-Hodgkin's lymphomas. , 1993, The American journal of pathology.

[52]  Jean Claude Zenklusen,et al.  A Practical Guide to The Cancer Genome Atlas (TCGA) , 2016, Statistical Genomics.

[53]  P. Wei,et al.  MYBL2 is an independent prognostic marker that has tumor-promoting functions in colorectal cancer. , 2015, American journal of cancer research.

[54]  R. González-Cámpora,et al.  Apoptosis in breast carcinoma. , 2000, Pathology, research and practice.

[55]  G. Fontanini,et al.  Apoptosis and proliferation in thyroid carcinoma: correlation with bcl-2 and p53 protein expression. , 1997, British Journal of Cancer.

[56]  S. Nordling,et al.  Ki-67, p53, Er-receptors, ploidy and S-phase as prognostic factors in T1 node negative breast cancer. , 1997, Acta oncologica.

[57]  V. Kosma,et al.  Apoptosis in breast cancer as related to histopathological characteristics and prognosis. , 1994, European journal of cancer.