title: Detection of cellular senescence within human invasive breast carcinomas distinguishes different breast tumor subtypes.
abstract: Oncogene-induced senescence is thought to act as a barrier to tumorigenesis by arresting cells at risk of malignant transformation. Nevertheless, numerous findings suggest that senescent cells may conversely promote tumor progression through the development of the senescence-associated secretome they produce. It is likely that the composition and the physiological consequences mediated by the senescence secretome are dependent on the oncogenes that trigger the senescence program. Breast cancer represents a heterogenous disease that can be divided into breast cancer subtypes due to different subsets of genetic and epigenetic abnormalities. As tumor initiation and progression of these breast cancer subtypes is triggered by diverse oncogenic stimuli, differences in the senescence secretomes within breast tumors might be responsible for tumor initiation, progression, metastasis and therapeutic response. Many studies have addressed the role of senescence as a barrier to tumor progression using murine xenograft models. However, few investigations have been performed to elucidate the degree to which senescent tumor cells are present within untreated human tumors, and if present, whether these senescent tumor cells may play a role in disease progression. In the present study we analysed the appearance of senescent cells within invasive breast cancers. Detection of cellular senescence by the use of SAβ-galactosidase (SAβ-gal) staining within invasive breast carcinoms from 129 untreated patients revealed differences in the amount of SAβ-gal+ tumor cells between breast cancer subtypes. The highest percentages of SAβ-gal+ tumor cells were found in HER2-positive and luminal A breast carcinomas whereas triple negative tumors showed either little or no positivity.
authors.affiliation: Institute of Pathology, University Medical Center, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Cristina L
authors.initials: CL
authors.lastname: Cotarelo
authors.affiliation: Institute of Pathology, University Medical Center, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Arno
authors.initials: A
authors.lastname: Schad
authors.affiliation: Institute of Pathology, University Medical Center, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Charles James
authors.initials: CJ
authors.lastname: Kirkpatrick
authors.affiliation: Centre for Biomedicine and Medical Technology Mannheim (CBTM), Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.|KIT Campus Nord, Institute for Toxicology and Genetics, Karlsruhe, Germany.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Sleeman
authors.affiliation: Institute of Pathology, University Medical Center, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Erik
authors.initials: E
authors.lastname: Springer
authors.affiliation: Department of Obstetrics and Gynecology, University Medical Center, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Schmidt
authors.affiliation: Centre for Biomedicine and Medical Technology Mannheim (CBTM), Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Thaler
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000235:genetics*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D034921:Lamin Type B / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009857:Oncogenes / Q000235:genetics*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D064726:Triple Negative Breast Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D034921:Lamin Type B; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53
keywords: breast cancer pathology; breast cancer subtypes; cellular senescence