Browse
Submit Data
Databases
API
Help

Dataset Information

11 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Integration of Ki-67 index into AJCC 2018 staging provides additional prognostic information in breast tumours candidate for genomic profiling.

ABSTRACT:

Background

The Eighth edition of the American Joint Committee on Cancer (AJCC) staging system (2018) for breast cancer (BC) introduced the prognostic stage. Moreover, multigene assessment has been indicated to tailor staging in T1/T2/N0, ER-positive/HER2-negative BC. However, many National Health Systems do not provide reimbursement for routine testing. The aim of this study was to assess whether Ki67 proliferation index is prognostically relevant for patients' candidacy for molecular testing.

Methods

A retrospective series of 686 ER+/HER2- BC were reclassified using AJCC 2018, and in the group of 521 patients for which AJCC 2018 recommends molecular evaluation, we assessed the prognostic efficacy of a prognostic stage enriched by Ki67 (Ki67-PS), considering Ki67 <20% an alternative to recurrence score <11 provided by Oncotype DX.

Results

We found that a group of BCs (35.6%, 58/163) assigned to IB stage by prognostic score were down classified to IA with Ki67-PS. The outcome of these 58 cases overlapped with that of lesions classified as stage IA using prognostic stage, showing a significantly better prognosis compared to IB tumours (HR = 2.79, p = 0.003).

Conclusions

These data suggest that Ki67 may be a reliable marker to enrich the 2018 AJCC prognostic score in BC patients' candidacy for genomic profiling.

SUBMITTER: Vissio E

PROVIDER: S-EPMC7000715 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Ki-67 gene expression.

Project description:Ki-67 serves as a prominent cancer marker. We describe how expression of the MKI67 gene coding for Ki-67 is controlled during the cell cycle. MKI67 mRNA and Ki-67 protein are maximally expressed in G2 phase and mitosis. Expression is dependent on two CHR elements and one CDE site in the MKI67 promoter. DREAM transcriptional repressor complexes bind to both CHR sites and downregulate the expression in G0/G1 cells. Upregulation of MKI67 transcription coincides with binding of B-MYB-MuvB and FOXM1-MuvB complexes from S phase into G2/M. Importantly, binding of B-MYB to the two CHR elements correlates with loss of CHR-dependent MKI67 promoter activation in B-MYB-knockdown experiments. In knockout cell models, we find that DREAM/MuvB-dependent transcriptional control cooperates with the RB Retinoblastoma tumor suppressor. Furthermore, the p53 tumor suppressor indirectly downregulates transcription of the MKI67 gene. This repression by p53 requires p21/CDKN1A. These results are consistent with a model in which DREAM, B-MYB-MuvB, and FOXM1-MuvB together with RB cooperate in cell cycle-dependent transcription and in transcriptional repression following p53 activation. In conclusion, we present mechanisms how MKI67 gene expression followed by Ki-67 protein synthesis is controlled during the cell cycle and upon induction of DNA damage, as well as upon p53 activation.

| S-EPMC8629999 | biostudies-literature

AJCC 8th edition prognostic staging provides no better discriminatory ability in prognosis than anatomical staging in triple negative breast cancer.

Project description:BACKGROUND:We retrospectively compared the prognostic value between the AJCC 8th edition anatomic (AS) and prognostic staging (PS) system for triple negative breast cancer (TNBC) in a cohort from two involved institutions and a large population database. METHODS:Clinicopathological data of TNBCs were identified in two involved institutions (SYSUCC-PWH cohort). Data from SEER database during 2010-2015 was also accessed. We restaged all cases into AS and PS group according to the AJCC 8th staging system. RESULTS:A total of 611 and 31,941 TNBCs were identified in two cohorts, with a median follow-up of 53.5 and 27 months respectively. PS upstaged 46.1% of patients in SYSUCC-PWH cohort, and 62.4% in SEER cohort. No significant difference was observed in C index between AS and PS models for disease-specific survival (DSS), progression-free survival (PFS) or overall survival (OS) in either cohort. χ2 statistic and Hazard Ratio for PFS, DSS and OS showed better discrimination between IA and IB, IIB and IIIA, IIIA and IIIB in AS model than PS model. Besides, patients with IIIC unchanged stage showed worse PFS compared to those with AS IIIA or IIIB upstaged to PS IIIC in both cohorts(p = 0.049, p < 0.001). CONCLUSIONS:Our findings demonstrated that prognostic staging system did not provide better discriminatory ability in predicting TNBCs prognosis than anatomic staging system.

| S-EPMC6945658 | biostudies-literature

The intrinsically disorderly story of Ki-67.

Project description:Ki-67 is one of the most famous marker proteins used by histologists to identify proliferating cells. Indeed, over 30 000 articles referring to Ki-67 are listed on PubMed. Here, we review some of the current literature regarding the protein. Despite its clinical importance, our knowledge of the molecular biology and biochemistry of Ki-67 is far from complete, and its exact molecular function(s) remain enigmatic. Furthermore, reports describing Ki-67 function are often contradictory, and it has only recently become clear that this proliferation marker is itself dispensable for cell proliferation. We discuss the unusual organization of the protein and its mRNA and how they relate to various models for its function. In particular, we focus on ways in which the intrinsically disordered structure of Ki-67 might aid in the assembly of the still-mysterious mitotic chromosome periphery compartment by controlling liquid-liquid phase separation of nucleolar proteins and RNAs.

| S-EPMC8354752 | biostudies-literature

Retinoblastoma Survival Following Primary Enucleation by AJCC Staging.

Project description:Primary enucleation of the eye with retinoblastoma is a widely accessible, life-saving treatment for retinoblastoma. This study evaluated the survival of patients following primary enucleation based on AJCC 8th edition staging. Included were 700 consecutive patients (700 eyes) treated with primary enucleation at 29 Chinese treatment centers between 2006 and 2015. Excluded were patients with less than one year follow-up, bilateral retinoblastoma, clinical evidence of extraocular disease at diagnosis, or prior focal or systemic therapy. The 5-year overall survival was 95.5%, and 5-year disease-specific survival (DSS) was 95.7%. Survival was better when enucleation was <26 days from diagnosis than delayed >26 days (96.1% vs. 86.9%; p = 0.017). Patients with eyes presenting with raised intraocular pressure with neovascularization and/or buphthalmos (cT3c) had worse 5-year DSS (87.1%) than those without (cT2b, 99.1%; cT3b, 98.7%; cT3d, 97.2%) (p < 0.05). The 5-year DSS based on pathological staging was pT1 (99.5%), pT2a (95.5%), pT3a (100%), pT3b (93.0%), pT3c/d (92.3%), and pT4 (40.9%). Patients with pT3 pathology who received six cycles of adjuvant chemotherapy had better 5-year DSS (97.7%) than those with no chemotherapy (88.1%; p = 0.06) and those who underwent 1-3 cycles (86.9%, p = 0.02) or 4-5 cycles (89.3%, p = 0.06). Patients with pT4 pathology who received six cycles of chemotherapy had better 5-year DSS than those with 0-5 cycles (63.6% vs. 16.7%; p = 0.02). Prompt primary enucleation yielded high long-term survival for children with retinoblastoma. The AJCC 8th edition staging is predictive of survival.

| S-EPMC8699512 | biostudies-literature

The cell proliferation antigen Ki-67 organises heterochromatin.

Project description:Antigen Ki-67 is a nuclear protein expressed in proliferating mammalian cells. It is widely used in cancer histopathology but its functions remain unclear. Here, we show that Ki-67 controls heterochromatin organisation. Altering Ki-67 expression levels did not significantly affect cell proliferation in vivo. Ki-67 mutant mice developed normally and cells lacking Ki-67 proliferated efficiently. Conversely, upregulation of Ki-67 expression in differentiated tissues did not prevent cell cycle arrest. Ki-67 interactors included proteins involved in nucleolar processes and chromatin regulators. Ki-67 depletion disrupted nucleologenesis but did not inhibit pre-rRNA processing. In contrast, it altered gene expression. Ki-67 silencing also had wide-ranging effects on chromatin organisation, disrupting heterochromatin compaction and long-range genomic interactions. Trimethylation of histone H3K9 and H4K20 was relocalised within the nucleus. Finally, overexpression of human or Xenopus Ki-67 induced ectopic heterochromatin formation. Altogether, our results suggest that Ki-67 expression in proliferating cells spatially organises heterochromatin, thereby controlling gene expression.

| S-EPMC4841783 | biostudies-literature

Heterogeneity of Diffusion-Weighted Imaging in Tumours and the Surrounding Stroma for Prediction of Ki-67 Proliferation Status in Breast Cancer.

Project description:Breast tissue heterogeneity is related to risk factors that lead to more aggressive tumour growth and worse prognosis, yet such heterogeneity has not been well characterized. The aim of this study is to reveal the heterogeneous signal patterns of the apparent diffusion coefficient (ADC) of a tumour and its surrounding stromal tissue and to predict the Ki-67 proliferation status in oestrogen receptor (ER)-positive breast cancer patients. A dataset of 82 patients who underwent diffusion-weighted imaging (DWI) examination was collected. The ADC map was segmented into regions comprising the tumour and the surrounding stromal shells. To reflect correlations between each region in terms of its mean ADC value, a functional graph was constructed consisting of nodes as regions and edges as interactions between two nodes. Analysis of the graph revealed a higher average degree in samples over-expressing Ki-67 than in samples with low Ki-67 expression. In the low-Ki-67 group, most of the identified edges represented correlations between adjacent regions, whereas additional edges representing correlations between non-adjacent regions were found in the high-Ki-67 group. The ADC signal in various breast stromal regions surrounding the tumour showed a discriminative pattern and would be valuable for estimating the Ki-67 proliferation status by DWI.

| S-EPMC5460128 | biostudies-literature

To Ki or Not to Ki: Re-Evaluating the Use and Potentials of Ki-67 for T Cell Analysis.

Project description:This study discusses substantive advances in T cell proliferation analysis, with the aim to provoke a re-evaluation of the generally-held view that Ki-67 is a reliable proliferation marker per se, and to offer a more sensitive and effective method for T cell cycle analysis, with informative examples in mouse and human settings. We summarize recent experimental work from our labs showing that, by Ki-67/DNA dual staining and refined flow cytometric methods, we were able to identify T cells in the S-G2/M phases of the cell-cycle in the peripheral blood (collectively termed "T Double S" for T cells in S-phase in Sanguine: in short "TDS" cells). Without our refinement, such cells may be excluded from conventional lymphocyte analyses. Specifically, we analyzed clonal expansion of antigen-specific CD8 T cells in vaccinated mice, and demonstrated the potential of TDS cells to reflect immune dynamics in human blood samples from healthy donors, and patients with type 1 diabetes, infectious mononucleosis, and COVID-19. The Ki-67/DNA dual staining, or TDS assay, provides a reliable approach by which human peripheral blood can be used to reflect the dynamics of human lymphocytes, rather than providing mere steady-state phenotypic snapshots. The method does not require highly sophisticated "-omics" capabilities, so it should be widely-applicable to health care in diverse settings. Furthermore, our results argue that the TDS assay can provide a window on immune dynamics in extra-lymphoid tissues, a long-sought potential of peripheral blood monitoring, for example in relation to organ-specific autoimmune diseases and infections, and cancer immunotherapy.

| S-EPMC8062736 | biostudies-literature

Corrigendum: To Ki or Not to Ki: Re-Evaluating the Use and Potentials of Ki-67 for T Cell Analysis.

Project description:[This corrects the article DOI: 10.3389/fimmu.2021.653974.].

| S-EPMC8507465 | biostudies-literature

Ki-67 Index Provides Long-Term Survival Information for Early-Stage HER2-Low-Positive Breast Cancer: A Single-Institute Retrospective Analysis.

Project description:AimIt has been reported that more than half of breast cancer (BC) could be identified as HER2-low-positive, which might be a distinct subtype. But the results are controversial. We aim to compare the survival outcomes between HER2-low-positive and HER2-0 BC with Asian women based on HR status or Ki-67 index.MethodsBetween January 2009 and December 2017, HER2-nonamplified BC in our single institute was identified. Patients were classified as HER2-low and HER2-0 cohort. Clinical characteristics were compared between these two groups and survival outcomes were calculated by the Kaplan-Meier method. We also performed subgroup analysis according to Ki-67 index and hormone-receptor (HR) status.ResultsOf the 2,230 included patients, 536 presented with HER2-0, and 1,694 with HER2-low positive. After a median follow-up of 85 months (range: 1-152 months), the 8-year OS, BCSS, and RFS of the overall cohort were 91%, 95%, and 89%, respectively. In comparison with the HER2-0 cohort, majority of HER2-low-expression BC concurrently presented with HR positive (82.3% vs. 69%, P < 0.001). There was no significant survival difference between the two groups in terms of OS, BCSS, and RFS (all p > 0.05). We then performed subgroup analysis according to HR status and Ki-67 index (<14% vs. ≥14%). Our results indicated that there was no significant survival difference between HER2-low-positive and HER2-0 tumors regardless of HR status (p > 0.05), while OS (p=0.026) and BCSS (p=0.052) of HER2-0 BC with high Ki-67 index were significantly poorer than that of HER2-low positive with high Ki-67, but not for RFS (p=0.17).ConclusionAmong early stage HER2-nonamplified BC, no significant survival difference could be found between HER2-low positive and HER2-0 cohort regardless of HR status. Survival outcomes of HER2-low positive with high Ki-67 seem to be poorer than that of HER2-0 tumors with high Ki-67 index.

| S-EPMC9489376 | biostudies-literature

Molecular subtyping of ependymoma and prognostic impact of Ki-67.

Project description:Although ependymomas (EPNs) have similar histopathology, they are heterogeneous tumors with diverse immunophenotypes, genetics, epigenetics, and different clinical behavior according to anatomical locations. We reclassified 141 primary EPNs from a single institute with immunohistochemistry (IHC) and next-generation sequencing (NGS). Supratentorial (ST), posterior fossa (PF), and spinal (SP) EPNs comprised 12%, 41%, and 47% of our cohort, respectively. Fusion genes were found only in ST-EPNs except for one SP-EPN with ZFTA-YAP1 fusion, NF2 gene alterations were found in SP-EPNs, but no driver gene was present in PF-EPNs. Surrogate IHC markers revealed high concordance rates between L1CAM and ZFTA-fusion and H3K27me3 loss or EZHIP overexpression was used for PFA-EPNs. The 7% cut-off of Ki-67 was sufficient to classify EPNs into two-tiered grades at all anatomical locations. Multivariate analysis also delineated that a Ki-67 index was the only independent prognostic factor in both overall and progression-free survivals. The gain of chromosome 1q and CDKN2A/2B deletion were associated with poor outcomes, such as multiple recurrences or extracranial metastases. In this study, we propose a cost-effective schematic diagnostic flow of EPNs by the anatomical location, three biomarkers (L1CAM, H3K27me3, and EZHIP), and a cut-off of a 7% Ki-67 labeling index.

| S-EPMC8752536 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data