Effect of Ki-67 Expression Levels and Histological Grade on Breast Cancer Early Relapse in Patients with Different Immunohistochemical-based Subtypes.
Ontology highlight
ABSTRACT:
SUBMITTER: Liang Q
PROVIDER: S-EPMC7203155 | biostudies-literature | 2020 May
REPOSITORIES: biostudies-literature
Publications
Effect of Ki-67 Expression Levels and Histological Grade on Breast Cancer Early Relapse in Patients with Different Immunohistochemical-based Subtypes.
Liang Qin Q Ma Ding D Gao Run-Fang RF Yu Ke-Da KD
Scientific reports 20200506 1
This retrospective analysis evaluated the interaction between Ki-67 and histological grade and their prognostic role in different breast cancer subtypes. In total, 2,573 breast cancer patients underwent surgery, and their histological grade and Ki-67 values were evaluated by breast pathologists. The median Ki-67 index was 15%, which was used as the cut-off for low/high Ki-67 expression. Recurrence-free survival (RFS) was calculated and compared, and the results indicated that Ki-67 expression wa ...[more]
Similar Datasets
Project description:ObjectiveTo build highly predictive performance models for glioma stratification with radiomics features from non-invasive MRI.MethodsT2-weighted fluid-attenuated inversion recovery (T2-FLAIR) imaging, diffusion-weighted MRI and diffusion kurtosis imaging were retrospectively collected for 139 glioma cases (2 with grade I, 67 with grade II, 36 with grade III and 34 with grade IV disease). Multi-parameter maps, including the apparent diffusion coefficient (ADC), mean diffusion coefficient (Dmean), fractional anisotropy (FA), and mean kurtosis (MK), were co-registered to T2-FLAIR, and 431 radiomics features for each were extracted within manually segmented tumour regions. Partial correlation analysis revealed correlations between radiomics features and glioma stratification factors (tumour grades and Ki-67 LI). Predictive models were built with adjusted-imbalanced logistic regression.ResultsMK radiomics features were more closely correlated with glioma stratification than other modalities analysed. The maximum R in MK was 0.52 for tumour grade and 0.56 for Ki-67 index (compared with 0.36 and 0.34 in FA, and 0.43 and 0.37 in ADC, and 0.48 and 0.42 in T2-FLAIR). The best predictive models for grade II vs. III, grade II vs. IV, low-grade vs. high-grade gliomas and positive vs. highly positive Ki-67 LI were obtained by combining multi-parameter MR radiomics features with AUCs of 0.858, 0.966, 0.853 and 0.870, respectively. However, for grade III vs. IV gliomas, the model obtained from MK radiomics features achieved the highest AUC (0.947), with excellent sensitivity and specificity.ConclusionCompared with the other modalities, MK showed closer correlations with tumour grade and Ki-67 LI. Combined radiomics models integrating multi-parameter MRI allow for the generation of highly predictive models for glioma stratification.
| S-EPMC8430185 | biostudies-literature
Project description:OBJECTIVES: To assess the immunohistochemical expression of Ki-67 and Proliferating Cell Nuclear Antigen (PCNA) as proliferative markers to study proliferative activity and CD34 as an endothelial cell marker in order to study vascular proliferation in astrocytomas in correlation with some clinicopathological parameters (age, gender, site of the tumor, and tumor grade). METHODS: A retrospective study wherein a total of 51 formalin-fixed paraffin-embedded brain astrocytoma excisional biopsies covering the period of June 2009 to February 2011 were retrieved from the archival materials of the Specialized Surgical Hospital in Medical City in Baghdad, Iraq. The histopathological diagnosis had been revised and all cases were stained by immunohistochemical technique with Ki-67, PCNA, and CD34 tumor markers. Values were considered statistically significant when p<0.05. RESULTS: Fibrillary astrocytoma (WHO grade II) was found to be the most common type among astrocytic tumors with the peak age incidence of astrocytomas found in the second and fifth decades of life, and a slight male predominance had been identified. There was a significant correlation between the age of the patients and the grade of the tumor, Ki-67 and PCNA labeling indices, and microvessel density (MVD) detected by CD34 (p<0.05). There was a highly significant correlation between Ki-67 and PCNA labeling indices in astrocytomas (p<0.001). CONCLUSION: A significant correlation was found between Ki-67, PCNA labeling indices, and MVD (microvessel density) detected by CD34, and between the clinicopathological variables of astrocytomas (age and grade of tumor). Hence, Ki-67 and PCNA, as markers for proliferation, and MVD as a marker of angiogenesis, could be used as ancillary methods in the differentiation of borderline grades of astrocytomas.
| S-EPMC3472582 | biostudies-other
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
Project description:IntroductionTriple negative breast cancer (TNBC) has a poorer survival, despite a higher response rate to neoadjuvant chemotherapy. The purpose of this study was to identify the predictive or prognostic value of Ki-67 among patients with TNBC treated with neoadjuvant chemotherapy, and the role of Ki-67 in further classification of TNBC.MethodsA total of 105 TNBC patients who received neoadjuvant docetaxel/doxorubicin chemotherapy were included in the present study. Pathologic complete response (pCR) rate, relapse-free survival (RFS), and overall survival (OS) were compared according to the level of Ki-67.ResultspCR was observed in 13.3% of patients. TNBC with high Ki-67 expression (? 10%) showed a higher pCR rate to neoadjuvant chemotherapy than TNBC with low Ki-67 expression. None of the low Ki-67 group achieved pCR (18.2% in the high Ki-67 group vs. 0.0% in the low Ki-67 group, P = 0.019). However, a high Ki-67 expression was significantly associated with poor RFS and OS in TNBC, despite a higher pCR rate (P = 0.005, P = 0.019, respectively). In multivariate analysis, high Ki-67 was an independent prognostic factor for RFS in TNBC (hazard ratio = 7.82, P = 0.002). The high Ki-67 group showed a similar pattern of recurrence with overall TNBC, whereas the low Ki-67 group demonstrated a relatively constant hazard rate for relapse.ConclusionsTNBC with high Ki-67 was associated with a more aggressive clinical feature despite a higher pCR rate. High proliferation index Ki-67 can be used for further classification of TNBC into two subtypes with different responses and prognosis.
| S-EPMC3219180 | biostudies-literature
Project description:Invasive lobular breast carcinoma is the second most common type of breast cancer after invasive ductal carcinoma. According to the American Cancer Society, more than 180,000 women in the United States find out they have invasive breast cancer each year. Personal history of breast cancer and certain changes in the breast are correlated with an increased breast cancer risk. The aim of this work was to analyze breastfeeding in patients with infiltrating lobular breast carcinoma, in relation with: 1) clinicopathological parameters, 2) hormonal receptors and 3) tissue-based tumor markers.The study included 80 women with ILC, 46 of which had breastfeed their children. Analyzed parameters were: age, tumor size, axillary lymph node (N), distant metastasis (M), histological grade (HG), estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), Ki-67, p53 and BCL2.ILC of non-lactating women showed a larger (p = 0.009), lymph node involvement (p = 0.051) and distant metastasis (p = 0.060). They were also more proliferative tumors measured by Ki-67 (p = 0.053). Breastfeeding history did not influence the subsequent behavior of the tumor regardless of histological subtype.Lactation seems to influence the biological characteristics of ILC defining a subgroup with more tumor size, axillary lymph node involvement, distant metastasis and higher proliferation measured by ki-67 expression.
| S-EPMC4786125 | biostudies-other
Project description:BackgroundThe neuropeptide substance P is a potential biomarker and therapeutic target in cancer. The main objectives of this study were to investigate the expression level of substance P in different breast cancer molecular subtypes and identify its association with clinicopathological parameters of patients and with Ki-67 index.MethodsA retrospective analysis was performed for a total of 164 paraffin-embedded breast cancer tissue samples [42 Her2/neu-enriched, 40 luminal A, 42 luminal B (triple-positive) and 40 triple negative subtypes]. The tissue microarray slides containing specimens were used to determine the expression of substance p and Ki-67 by immunohistochemical staining.ResultsThe mean age of the cohort was 51.35 years. Twenty two percent of cases had low substance P expression levels (TS ≤ 5), while 78% had high expression levels (TS > 5). A significant association was found between SP expression level and breast cancer molecular subtype (p = 0.002), TNM stage (p = 0.034), pN stage (p = 0.013), axillary lymph node metastasis (p = 0.004), ER and PR statuses (p<0.001) and history of DCIS (p = 0.009). The average percentage of Ki-67 expression was 27.05%. When analyzed as a continuous variable, significant differences were observed between the mean Ki-67 scores and molecular subtype (p = 0.001), grade (p = 0.003), pN stage (p = 0.007), axillary lymph node metastasis (p = 0.001), and ER and PR statuses (p <0.001).ConclusionSP is overexpressed in most of the analyzed tissues and has a negative prognostic value in the breast cancer patients. Besides substance P is a potential therapeutic target in breast cancer.
| S-EPMC8177477 | biostudies-literature
Project description:IntroductionKi-67 labeling index assessed by immunohistochemical assays has been shown useful in assessing the risk of recurrence for estrogen receptor (ER)-positive HER2-negative breast cancers (BC) and distinguishing Luminal A-like from Luminal B-like tumors. We aimed to assess the performance of the Ventana CONFIRM anti-Ki-67 (30-9) Rabbit Monoclonal Primary Antibody.MethodsWe constructed a case-cohort design based on a random sample (n?=?679) of all patients operated on for a first primary, non-metastatic, ER-positive, HER2-negative BC at the European Institute of Oncology (IEO) Milan, Italy during 1998-2002 and all additional patients (n?=?303) operated during the same period, who developed an event (metastasis in distant organs or death due to BC as primary event) and were not included in the previous subset. Multivariable Cox proportional hazards regression with inverse subcohort sampling probability weighting was used to evaluate the risk of event according to Ki-67 (30-9) and derived intrinsic molecular subtype, using previously defined cutoff values, i.e., respectively 14% and 20%.ResultsKi-67 was?<?14% in 318 patients (32.4%), comprised between 14 and 19% in 245 patients (24.9%) and???20 in 419 patients (42.7%). At multivariable analysis, the risk of developing distant disease was 1.88 (95% CI 1.20-2.93; P?=?0.006) for those with Ki-67 comprised between 14 and 19%, and 3.06 (95% CI 1.93-4.84; P?<?0.0001) for those with Ki-67???20% compared to those with Ki-67?<?14%. Patients with Luminal B-like BC had an approximate twofold risk of developing distant disease (HR?=?1.91; 95% CI 1.35-2.71; P?=?0.0003) than patients with Luminal A-like BC defined using Ki-67 (30-9).ConclusionsKi-67 evaluation using the 30-9 rabbit monoclonal primary antibody was able to stratify patients with ER-positive HER2-negative BC into prognostically distinct groups. Ki-67 assessment, with strict adherence to the international recommendations, should be included among the clinically useful biological parameters for the best treatment of patients with BC.
| S-EPMC6797656 | biostudies-literature
Project description:BackgroundKi-67 is increasingly being used as a response biomarker in window of opportunity, pre-surgical trials for breast cancer patients. Since Ki-67 is often higher at surgery than at baseline core biopsy in subjects allocated to placebo, we investigated which factors affected this change.Patients and methodsWe retrieved data from 274 patients who received no active treatment in three consecutive pre-surgical trials from a single institution. We assessed the association between changes in Ki-67 from diagnostic biopsy to surgical specimen and the following factors: age, body mass index, tumor prognostic and predictive factors, including immunohistochemical molecular subtype, number and size of biopsy specimens, time from biopsy to surgery, circulating insulin-like growth factor-I, sex hormone-binding globulin and hsCRP.ResultsA total of 269 patients with paired measures of Ki-67 at biopsy and surgery were analyzed. Overall, the mean (±SD) change was 2.2 ± 9.2% after a median interval of 41 days (inter-quartile range 33-48). Molecular subtype was the only factor associated with a significant change of Ki-67 (P = 0.004), with a mean absolute increase of 5.3% [95% confidence interval (CI): 2.3-8.3, P = 0.0005] in estrogen receptor-negative HER2-positive tumors (n = 36) and 5.4% (95% CI: 2.9-7.9, P < 0.0001) in triple-negative tumors (n = 78). No significant change in luminal-A (n = 46), luminal-B (n = 85) and luminal-B HER2-positive (n = 24) tumors was observed.ConclusionsA significant increase in Ki-67 from baseline biopsy to end point surgery in untreated subjects was ascertained in HER2-positive and triple-negative tumors. This biological association suggests a real increase in cancer proliferation, possibly as a result of a biopsy-driven wound healing effect, and should be considered in the design and interpretation of pre-surgical studies.Registered clinical trial numbersISRCTN86894592; ISRCTN16493703.
| S-EPMC4433505 | biostudies-literature
Project description:Ki-67 is considered as one of prime biomarkers to reflect cell proliferation and immunohistochemical Ki-67 staining has been widely applied in clinical pathology. To solve the widespread controversy whether Ki-67 reactivity significantly predicts clinical prognosis of bladder carcinoma (BC), we performed a comprehensive meta-analysis by combining results from different literature. A comprehensive search was conducted in the Chinese databases of WanFang, China National Knowledge Infrastructure and Chinese VIP as well as English databases of PubMed, ISI web of science, EMBASE, Science Direct, and Wiley online library. Independent studies linking Ki-67 to cancer-specific survival (CSS), disease-free survival (DFS), overall survival (OS), progression-free survival (PFS), and recurrence-free survival (RFS) were included in our meta-analysis. With the cut-off values literature provided, hazard ratio (HR) values between the survival distributions were extracted and later combined with STATA 12.0. In total, 76 studies (n?=?13,053 patients) were eligible for the meta-analysis. It was indicated in either univariate or multivariate analysis for survival that high Ki-67 reactivity significantly predicted poor prognosis. In the univariate analysis, the combined HR for CSS, DFS, OS, PFS, and RFS were 2.588 (95% confidence interval [CI]: 1.623-4.127, P?<?0.001), 2.697 (95%CI: 1.874-3.883, P?<?0.001), 2.649 (95%CI: 1.632-4.300, P?<?0.001), 3.506 (95%CI: 2.231-5.508, P?<?0.001), and 1.792 (95%CI: 1.409-2.279, P?<?0.001), respectively. The pooled HR of multivariate analysis for CSS, DFS, OS, PFS, and RFS were 1.868 (95%CI: 1.343-2.597, P?<?0.001), 2.626 (95%CI: 2.089-3.301, P?<?0.001), 1.104 (95%CI: 1.008-1.209, P?=?0.032), 1.518 (95%CI: 1.299-1.773, P?<?0.001), and 1.294 (95%CI: 1.203-1.392, P?<?0.001), respectively. Subgroup analysis of univariate analysis by origin showed that Ki-67 reactivity significantly correlated with all 5 clinical outcome in Asian and European-American patients (P?<?0.05). For multivariate analysis, however, the pooled results were only significant for DFS, OS, and RFS in Asian patients, for CSS, DFS, PFS, and RFS in European-American patients (P?<?0.05). In the subgroup with low cut-off value (<20%), our meta-analysis indicated that high Ki-67 reactivity was significantly correlated with worsened CSS, DFS, OS, PFS, and RFS on univariate analysis (P?<?0.05). For multivariate analysis, the meta-analysis of literature with low cut-off value (<20%) demonstrated that high Ki-67 reactivity predicted shorter DFS, PFS, and RFS in BC patients (P?<?0.05). In the subgroup analysis of high cut-off value (?20%), our meta-analysis indicated that high Ki-67 reactivity, in either univariate or multivariate analysis, significantly correlated with all five clinical outcomes in BC patients (P?<?0.05). The meta-analysis indicates that high Ki-67 reactivity significantly correlates with deteriorated clinical outcomes in BC patients and that Ki-67 can be considered as an independent indicator for the prognosis by the meta-analyses of multivariate analysis.
| S-EPMC4839831 | biostudies-literature
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