Immunohistochemical Ki67 labeling index has similar proliferation predictive power to various gene signatures in breast cancer.
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ABSTRACT:
SUBMITTER: Niikura N
PROVIDER: S-EPMC7659300 | biostudies-literature | 2012 Aug
REPOSITORIES: biostudies-literature
Publications
Immunohistochemical Ki67 labeling index has similar proliferation predictive power to various gene signatures in breast cancer.
Niikura Naoki N Iwamoto Takayuki T Masuda Shinobu S Kumaki Nobue N Xiaoyan Tang T Shirane Masatoshi M Mori Kazushige K Tsuda Banri B Okamura Takuho T Saito Yuki Y Suzuki Yasuhiro Y Tokuda Yutaka Y
Cancer science 20120614 8
The objective of this study was to examine the association between the immunohistochemical Ki67 labeling index (IHC Ki67), Ki67 mRNA expression level, and first-generation gene signatures in a cohort of breast cancer patients. We assessed associations between IHC Ki67 and first-generation gene signatures in a panel of 39 tumor samples, using an oligonucleotide microarray. Gene expression analyses included Ki67 alone (MKi67), 21-gene signature, mitosis kinome score signature, and genomic grade in ...[more]
Similar Datasets
Project description:In this work, a novel proliferation index (PI) calculator for Ki67 images called piNET is proposed. It is successfully tested on four datasets, from three scanners comprised of patches, tissue microarrays (TMAs) and whole slide images (WSI), representing a diverse multi-centre dataset for evaluating Ki67 quantification. Compared to state-of-the-art methods, piNET consistently performs the best over all datasets with an average PI difference of 5.603%, PI accuracy rate of 86% and correlation coefficient R = 0.927. The success of the system can be attributed to several innovations. Firstly, this tool is built based on deep learning, which can adapt to wide variability of medical images-and it was posed as a detection problem to mimic pathologists' workflow which improves accuracy and efficiency. Secondly, the system is trained purely on tumor cells, which reduces false positives from non-tumor cells without needing the usual pre-requisite tumor segmentation step for Ki67 quantification. Thirdly, the concept of learning background regions through weak supervision is introduced, by providing the system with ideal and non-ideal (artifact) patches that further reduces false positives. Lastly, a novel hotspot analysis is proposed to allow automated methods to score patches from WSI that contain "significant" activity.
| S-EPMC7792768 | biostudies-literature
Project description:BackgroundKi67 labeling index (LI) is critical for treatment options and prognosis evaluation in breast cancer. Visual assessment (VA) is widely used to assess Ki67 LI, but has some limitations. In this study, we compared the consistency between VA and automated digital image analysis (DIA) of Ki67 LI in breast cancer, and to evaluate the application value of DIA in Ki67 LI assessment.MethodsKi67 immunostained slides of 155 cases of primary invasive breast cancer were eyeballing assessed by five breast pathologists and automated digital image analyzed by one breast pathologist respectively. Two score methods, hot-spot score and average score, were used to choose score areas. The intra-class correlation coefficient (ICC) was used to analyze the consistency between VA and DIA, and Wilcoxon signed-rank test was used to compare the median of paired-difference between VA and DIA values.Results(1) A perfect agreement was demonstrated between VA and DIA of Ki67 LI by ICC analysis (P<0.0001) in the whole cohort. A perfect agreement between VA and DIA of Ki67 LI was also showed in G2-G3, ER positive/HER2 negative cases. Average score and hot-spot score methods both demonstrated a perfect concordance between VA and DIA of Ki67 LI. (2) All cases were classified into three groups by VA values (?10%, 11%-30% and >30% Ki67 LI). The concordance was relatively lower in intermediate Ki67 LI group (11%-30%) compared with high (>30%) Ki67 LI groups according to both methods. (3) All cases were classified into three groups by paired-difference (d) between VA values of hot-spot score and average score (d<5, 5?d<10, d?10) to evaluate the correlation between Ki67 staining distribution (heterogeneous or homogenous) and reproducibility of assessment. A perfect agreement was all demonstrated in three groups, and a slightly better Ki67 LI agreement between VA and DIA was indicated in homogenous staining slides than in heterogeneous staining ones. (4) VA values were relatively smaller than DIA values (average score: median of paired-difference -3.72; hot-spot score: median of paired-difference -9.12).ConclusionsAn excellent agreement between VA and DIA of Ki67 LI in breast cancer was demonstrated in the whole mixed cohort, suggesting that VA and DIA both could be used to assess Ki67 LI in clinical practice. Average score and hot-spot score methods both demonstrated a perfect concordance between VA and DIA of Ki67 LI. The almost perfect agreement between VA and DIA was observed in high Ki67 LI cases, displaying a homogenous staining pattern. The consistency between VA and DIA was relatively low in intermediate Ki67 LI group. The heterogeneity of tumors may slightly affect the concordance between VA and DIA of Ki67 LI. Assessment of VA provides lower Ki67 values than DIA, the biological importance of these values are not known at the moment.
| S-EPMC4771161 | biostudies-literature
Project description:BackgroundAdjuvant chemotherapy has been shown to produce a favorable prognosis for patients with resectable mucosal melanoma (MM), resulting in the need for stratification to optimally select patients to benefit from adjuvant therapy. This study analyzed Ki67 as a potential stratification index for adjuvant chemotherapy in resectable MM.MethodsPatients with resected MM who received subsequent adjuvant therapy in Beijing Cancer Hospital between 2010 and 2018 were retrospectively enrolled and analyzed. Relapse-free survival (RFS) and melanoma-specific survival (MSS) curves were used to perform the survival comparisons across different subgroups.ResultsFrom Jan 2010 to Dec 2018, 1106 MM patients were screened from a database of 4706 patients and 175 of these patients were finally enrolled. A total of 100 patients received temozolomide (TMZ)-based adjuvant chemotherapy and 75 patients received high-dose interferon-α2b (HDI) adjuvant therapy. Compared with HDI, patients who received TMZ-based adjuvant chemotherapy had significantly superior RFS (21.0 vs. 9.6 months, P = 0.002). For patients with low Ki67 expression (<30%), the two regimens showed no significant difference for impact on RFS (33.9 vs. 22.7 months, P = 0.329). However, for patients with high Ki67 expression (≥30%), TMZ-based adjuvant chemotherapy achieved favorable RFS compared with HDI (18.0 vs. 6.7 months, P < 0.001) and tended to improve MSS compared to HDI (41.4 vs. 25.1 months, P = 0.067).ConclusionCompared with HDI, adjuvant chemotherapy may be more relevant for patients with Ki67 ≥ 30%. Ki67 may serve as a potential index to distinguish populations benefiting from adjuvant chemotherapy in resectable MM, and may provide a basis for stratification in the selection of adjuvant regimens.
| S-EPMC9280123 | biostudies-literature
Project description:Ki67, a nuclear proliferation-related protein, is heavily used in anatomic pathology but has not become a companion diagnostic or a standard-of-care biomarker due to analytic variability in both assay protocols and interpretation. The International Ki67 Working Group in breast cancer has published and has ongoing efforts in the standardization of the interpretation of Ki67, but they have not yet assessed technical issues of assay production representing multiple sources of variation, including antibody clones, antibody formats, staining platforms, and operators. The goal of this work is to address these issues with a new standardization tool. We have developed a cell line microarray system in which mixes of human Karpas 299 or Jurkat cells (Ki67+) with Sf9 (Spodoptera frugiperda) (Ki67-) cells are present in incremental standardized ratios. To validate the tool, six different antibodies, including both ready-to-use and concentrate formats from six vendors, were used to measure Ki67 proliferation indices using IHC protocols for manual (bench-top) and automated platforms. The assays were performed by three different laboratories at Yale and analyzed using two image analysis software packages, including QuPath and Visiopharm. Results showed statistically significant differences in Ki67 reactivity between each antibody clone. However, subsets of Ki67 assays using three clones performed in three different labs show no significant differences. This work shows the need for analytic standardization of the Ki67 assay and provides a new tool to do so. We show here how a cell line standardization system can be used to normalize the staining variability in proliferation indices between different antibody clones in a triple negative breast cancer cohort. We believe that this cell line standardization array has the potential to improve reproducibility among Ki67 assays and laboratories, which is critical for establishing Ki67 as a standard-of-care assay.
| S-EPMC8222064 | biostudies-literature
Project description:BACKGROUND:The protein ki67 (pki67) is a marker of tumor aggressiveness, and its expression has been proven to be useful in the prognostic and predictive evaluation of several types of tumors. To numerically quantify the pki67 presence in cancerous tissue areas, pathologists generally analyze histochemical images to count the number of tumor nuclei marked for pki67. This allows estimating the ki67-index, that is the percentage of tumor nuclei positive for pki67 over all the tumor nuclei. Given the high image resolution and dimensions, its estimation by expert clinicians is particularly laborious and time consuming. Though automatic cell counting techniques have been presented so far, the problem is still open. RESULTS:In this paper we present a novel automatic approach for the estimations of the ki67-index. The method starts by exploiting the STRESS algorithm to produce a color enhanced image where all pixels belonging to nuclei are easily identified by thresholding, and then separated into positive (i.e. pixels belonging to nuclei marked for pki67) and negative by a binary classification tree. Next, positive and negative nuclei pixels are processed separately by two multiscale procedures identifying isolated nuclei and separating adjoining nuclei. The multiscale procedures exploit two Bayesian classification trees to recognize positive and negative nuclei-shaped regions. CONCLUSIONS:The evaluation of the computed results, both through experts' visual assessments and through the comparison of the computed indexes with those of experts, proved that the prototype is promising, so that experts believe in its potential as a tool to be exploited in the clinical practice as a valid aid for clinicians estimating the ki67-index. The MATLAB source code is open source for research purposes.
| S-EPMC6935242 | biostudies-literature
Project description:BackgroundInflammation is believed to influence human colorectal carcinogenesis and may have an impact on prognosis and survival. The mucosal immunophenotype in dogs with colorectal cancer is poorly described. The aim of this study was to investigate whether the density, distribution and grade of tumor-infiltrating immune cells (TIIs) are different in normal colonic tissue vs benign stages (adenomas) and malignant stages (adenocarcinomas) of canine colorectal carcinogenesis, and thus, whether they can be considered as prognostic factors in dogs. This retrospective case-control study was performed on formalin-fixed, paraffin-embedded tissue samples from dogs with histologically confirmed colorectal adenoma (n = 18) and adenocarcinoma (n = 13) collected from archived samples. The samples had been collected by colonoscopy, surgery or during postmortem examination. Healthy colonic tissue obtained post mortem from dogs euthanized for reasons not involving the gastrointestinal tract served as control tissue (n = 9).ResultsThe tumor samples had significantly lower numbers of CD3+ T-cells in the epithelium compared to controls (adenocarcinoma vs control, Kruskal-Wallis test, p = 0.0004, and adenoma vs control, p = 0.002). Adenomas had a significantly lower number of CD18+ cells in the lamina propria, compared to control samples (Kruskal-Wallis test, p = 0.008). Colonic samples from control dogs had uniform staining of β-catenin along the cell membrane of epithelial cells. Compared to normal colonic cells, the expression levels of cytoplasmic β-catenin were significantly higher in adenomas and adenocarcinomas (adenoma vs control Kruskal-Wallis test, p = 0.004, and adenocarcinoma vs control, p = 0.002). None of the control samples showed positive staining of β-catenin in the nucleus of colonic cells. In contrast, adenocarcinomas and adenomas showed moderate to strong staining of the cell nucleus. The nuclear β-catenin expression (signal strength and distribution) was significantly higher in adenomas compared to adenocarcinomas (Kruskal-Wallis test, p < 0.05).Conclusionsβ-catenin and Ki67 were not useful markers for demonstrating tumor progression from adenomas to adenocarcinomas. The lower presence of CD18 and CD3+ cells in colorectal tumors compared to controls indicates a reduced presence of histiocytes and T-cells, which may have implications for the pathogenesis and progression of colorectal cancer in dogs.
| S-EPMC7953700 | biostudies-literature
Project description:Our objective was to examine the usefulness of the Ki67 proliferation index as a prognostic marker in patients with medullary thyroid carcinoma (MTC). It is difficult to predict the prognosis of MTC by using conventional prognostic factors. Immunocytochemical analysis of tumour proliferation has been used as a prognostic tool in some tumours, but only rarely in MTC. In all, 71 tumours from 36 patients were investigated, by using a semiautomatic image analysis programme. On average 10,000 nuclear profiles were counted per tumour, and the percentage of tumour cells expressing the proliferation marker, Ki67, was calculated. Primary tumours that had metastasised had higher Ki67 indices than primary tumours that had not metastasised. Recurrent lymph node metastasis had higher Ki67 indices than the primary tumours. By using a Poisson model, it was possible to estimate the median survival time for individual patients if the Ki67 index for the primary tumour and the age at surgery were known. The higher the Ki67 index and the age at operation were, the shorter was the survival. Estimating the median survival of individual patients will be of help for planning the patients' life and postoperative follow-up and treatment.
| S-EPMC2376863 | biostudies-other
Project description:While body mass index (BMI) is the most widely used anthropometric measure, its association with all-cause mortality is generally J-shaped or U-shaped. A body shape index (ABSI) is a recently formulated anthropometric measure that shows linear relationship to all-cause mortality, especially in Caucasian cohorts. We aimed to address the relationship between ABSI and all-cause mortality in Asians and to assess the influence of sex difference and of chronic kidney disease (CKD) on this relationship.This was a longitudinal cohort study assessing the association of ABSI, BMI, waist circumference (WC), and waist-to-height ratio (WHtR) with all-cause mortality in a Japanese nationwide Specific Health Checkup database. The study enrolled 160,625 participants followed-up between 2008 and 2012. We calculated the all-cause mortality risk associated with a 1-standard deviation increase (+1SD) in ABSI, BMI, WC, or WHtR in cohorts stratified by sex and the presence of CKD.During the 4-year follow up, 1.3% of participants died. In men, ABSI (+1SD) significantly increased the risk for all-cause mortality after adjusting for other known risk factors including CKD; hazard ratio (HR) and 95% confidence intervals (CI) of non-CKD cohort, 1.30 (1.18 to 1.43), p<0.01; HR and 95%CI of CKD cohort, 1.16 (1.01 to 1.34), p = 0.04. In women, ABSI (+1SD) did not show significant association with all-cause mortality, especially in the CKD cohort; HR and 95% CI of non-CKD cohort, 1.07 (0.99 to 1.17), p = 0.09; HR and 95%CI of CKD cohort, 0.98 (0.84 to 1.14), p = 0.78. Conversely, BMI (+1SD) was associated with significantly lower risk in men, although minimal association was found in women. WC and WHtR showed little association with all-cause mortality. On stratification per ABSI quartiles, mortality risk increased linearly and significantly with ABSI in men, but not in women with CKD. Both BMI and WC showed significant but U-shaped association with mortality in the non-CKD cohort and in men with CKD. WHtR also showed significant U-shaped association with mortality in men.In the Japanese population, ABSI showed significant and linear correlation with mortality risk in men but not in women, especially in the presence of CKD.
| S-EPMC5433760 | biostudies-literature
Project description:Background and purposeKi-67 labeling index (LI) is an important indicator of tumor cell proliferation in glioma, which can only be obtained by postoperative biopsy at present. This study aimed to explore the correlation between Ki-67 LI and apparent diffusion coefficient (ADC) parameters and to predict the level of Ki-67 LI noninvasively before surgery by multiple MRI characteristics.MethodsPreoperative MRI data of 166 patients with pathologically confirmed glioma in our hospital from 2016 to 2020 were retrospectively analyzed. The cut-off point of Ki-67 LI for glioma grading was defined. The differences in MRI characteristics were compared between the low and high Ki-67 LI groups. The receiver operating characteristic (ROC) curve was used to estimate the accuracy of each ADC parameter in predicting the Ki-67 level, and finally a multivariate logistic regression model was constructed based on the results of ROC analysis.ResultsADCmin, ADCmean, rADCmin, rADCmean and Ki-67 LI showed a negative correlation (r = - 0.478, r = - 0.369, r = - 0.488, r = - 0.388, all P < 0.001). The Ki-67 LI of low-grade gliomas (LGGs) was different from that of high-grade gliomas (HGGs), and the cut-off point of Ki-67 LI for distinguishing LGGs from HGGs was 9.5%, with an area under the ROC curve (AUROC) of 0.962 (95%CI 0.933-0.990). The ADC parameters in the high Ki-67 group were significantly lower than those in the low Ki-67 group (all P < 0.05). The peritumoral edema (PTE) of gliomas in the high Ki-67 LI group was higher than that in the low Ki-67 LI group (P < 0.05). The AUROC of Ki-67 LI level assessed by the multivariate logistic regression model was 0.800 (95%CI 0.721-0.879).ConclusionsThere was a negative correlation between ADC parameters and Ki-67 LI, and the multivariate logistic regression model combined with peritumoral edema and ADC parameters could improve the prediction ability of Ki-67 LI.
| S-EPMC9922464 | biostudies-literature
Project description:AimsPhosphohistone H3 (PhH3) has been proposed as a novel proliferation marker in breast cancer. This study compares the interobserver agreement for assessment of the mitotic activity index (MAI), Ki67 expression, and PhH3 in a cohort of oestrogen receptor (ER)-positive breast cancer patients.Methods and resultsTumour samples of 159 luminal breast cancer patients were collected. MAI and PhH3 scores were assessed by three breast cancer pathologists. Ki67 scores were assessed separately by two of the three pathologists. PhH3-positive cells were counted in an area of 2 mm2 , with a threshold of ≥13 positive cells being used to discriminate between low-proliferative and high-proliferative tumours. Ki67 expression was assessed with the global scoring method. Ki67 percentages of <20% were considered to be low. The intraclass correlation coefficient (ICC) and Cohen's κ statistics were used to evaluate interobserver agreement. The impact on histological grading of replacing the MAI with PhH3 was assessed. Counting PhH3-positive cells was highly reproducible among all three observers (ICC of 0.86). The κ scores for the categorical PhH3 count (κ = 0.78, κ = 0.68, and κ = 0.80) reflected substantial agreement among all observers, whereas agreement for the MAI (κ = 0.38, κ = 0.52, and κ = 0.26) and Ki67 (κ = 0.55) was fair to moderate. When PhH3 was used to determine the histological grade, agreement in grading increased (PhH3, κ = 0.52, κ = 0.48, and κ = 0.52; MAI, κ = 0.43, κ = 0.35, and κ = 0.32), and the proportion of grade III tumours increased (14%, 18%, and 27%).ConclusionPhH3 seems to outperform Ki67 and the MAI as a reproducible means to measure tumour proliferation in luminal-type breast cancer. Variation in the assessment of histological grade might be reduced by using PhH3, but would result in an increase in the proportion of high-grade cancers.
| S-EPMC7539961 | biostudies-literature