Ki-67 Group Research Articles

Correlations between DKI and DWI with Ki-67 in gastric adenocarcinoma.

Diffusion kurtosis imaging (DKI) has been applied for gastric adenocarcinoma. Correlations between its parameters and Ki-67 are unclear. To investigate the correlation between DKI and diffusion-weighted imaging (DWI) parameters with the Ki-67 index in gastric adenocarcinoma. A total of 54 patients with gastric adenocarcinoma were enrolled in the study and underwent DWI and DKI at 3.0-T MRI before surgery. Based on the settings of the regions of interest, the DWI and DKI parameters (including apparent diffusion coefficient [ADC], diffusion kurtosis [K], and diffusion coefficient [DK]) of each patient's gastric adenocarcinoma were measured and calculated. The participants were divided into two groups (low Ki-67 group and high Ki-67 groups). The intraclass correlation coefficient (ICC) and independent-sample t-test were used to compare differences in each parameter between two groups. Spearman's correlation coefficient was calculated to determine the correlation between Ki-67 and the parameters. Each parameter was compared using the area under the receiver operating characteristic curve. All parameters were included in the multivariate logistic regression analysis to explore the relationship between each parameter and high Ki-67 index. ADC and DK were negatively relevant with Ki-67 and K was positively relevant with Ki-67 in gastric adenocarcinoma. ADC, DK, and K had diagnostic efficiency in differentiating the low Ki-67 group from the high Ki-67 group. A higher K value independently predicted a high Ki-67 status. DWI and DKI reflected the proliferative characteristics of gastric adenocarcinoma. K was the strongest independent factor for predicting high Ki-67 status.

Reproducibility of CT radiomic features in lung neuroendocrine tumours (NETs) patients: analysis in a heterogeneous population

BackgroundThe aim is to find a correlation between texture features extracted from neuroendocrine (NET) lung cancer subtypes, both Ki-67 index and the presence of lymph-nodal mediastinal metastases detected while using different computer tomography (CT) scanners.MethodsSixty patients with a confirmed pulmonary NET histological diagnosis, a known Ki-67 status and metastases, were included. After subdivision of primary lesions in baseline acquisition and venous phase, 107 radiomic features of first and higher orders were extracted. Spearman’s correlation matrix with Ward’s hierarchical clustering was applied to confirm the absence of bias due to the database heterogeneity. Nonparametric tests were conducted to identify statistically significant features in the distinction between patient groups (Ki-67 < 3—Group 1; 3 ≤ Ki-67 ≤ 20—Group 2; and Ki-67 > 20—Group 3, and presence of metastases).ResultsNo bias arising from sample heterogeneity was found. Regarding Ki-67 groups statistical tests, seven statistically significant features (p value < 0.05) were found in post-contrast enhanced CT; three in baseline acquisitions. In metastasis classes distinction, three features (first-order class) were statistically significant in post-contrast acquisitions and 15 features (second-order class) in baseline acquisitions, including the three features distinguishing between Ki-67 groups in baseline images (MCC, ClusterProminence and Strength).ConclusionsSome radiomic features can be used as a valid and reproducible tool for predicting Ki-67 class and hence the subtype of lung NET in baseline and post-contrast enhanced CT images. In particular, in baseline examination three features can establish both tumour class and aggressiveness.

The Potential Value of Ki-67 in Prognostic Classification in Early Low-Risk Endometrial Cancer.

This study aims to determine the optimal cut-off value of Ki-67 to better predict the recurrence of early low-risk endometrial cancer (EC). Seven hundred and forty-eight patients diagnosed with low-risk EC from West China Second Hospital of Sichuan University and the First Affiliated Hospital of Chongqing Medical University were retrospectively analyzed. The receiver operating characteristic curve (ROC) and Youden index were used to calculate the optimal cut-off value of Ki-67 expression. The clinicopathological indexes between two groups divided by cut-off value of Ki-67 were compared. The univariate and multivariate regression analyses were performed to investigate risk factors connected to the recurrence of early low-risk EC. The survival analysis was shown in Kaplan-Meier curve. Thirty-three patients were detected with tumor recurrence after primary surgery (4.4%); 33% was the optimal cut-off value of the Ki-67 index. A high Ki-67 was significantly associated with age (P = .002), myometrial invasion (P < .001), and the expression of P53 (P = .007). The multivariate regression analysis verified that Ki67 ≥ 33% was an independent prognostic factor for predicting recurrence. The recurrence-free survival (RFS) and the overall survival (OS) in high Ki-67 group was significantly lower than that in low Ki-67 group (P < .001 and P = .029, respectively). The prognostic values of ER, PR, and P53 in combination with Ki-67 were superior to each single predictor. The optimal cut-off value of Ki-67 for predicting recurrence is 33%, which quantitatively defines the specific value of Ki-67 that causes high-risk recurrence in early low-risk EC.

TWO DIFFERENT CHARACTERISTICS AND PROGNOSIS OF GRADE 3 GASTROENTEROPANCREATIC NEUROENDOCRINE TUMORS: Erciyes Multidisiplinary Neuroendocrine Tumor (NET) Group Experience

Grade 3 gastroenteropancreatic neuroendocrine tumors (GEPNETs) are not a homogenous group. We aimed to determine clinicopathologic, survival and prognostic differences in metastatic grade 3 GEPNETs with the help of ki67 and GA68PET CT/octreoscan. We divided patients diagnosed metastatic grade 3 GEPNETs into two groups based on the ki67 cut-off point 47 as ki67 low and high. And we divided into 2 groups again according to scan positivity. And we compared all four groups according to clinicopathologic characteristics, survival and prognostic factors. We included 26 patients into our study. The median overall survival in low group was 20 and 10 months in high group (p=0,321). Lower ki67 scan positive group had longer overall survival than lower ki67 scan negative group (NR vs 3 months, respectively, p=0.067) and in high ki67 group the median overall survival was longer in scan positive than negative group (10 vs 9,respectively, p=0.956). The median overall survival was longer in patients with low ki67 levels compared to high ki67 levels. The best overall survival was in low ki67 and scan positive group.

Prediction of the Ki-67 marker index in hepatocellular carcinoma based on Dynamic Contrast-Enhanced Ultrasonography with Sonazoid

BackgroundKi-67 is widely used as a proliferative and prognostic factor in HCC. This study aimed to analyze the relationship between dynamic contrast-enhanced ultrasonography (DCE-US) parameters and Ki-67 expression.MethodsOne hundred and twenty patients with histopathologically confirmed HCC who underwent DCE-US were included in this prospective study. Patients were classified according to the Ki-67 marker index into low Ki-67 (< 10%) (n = 84) and high Ki-67 (≥ 10%) groups (n = 36). Quantitative perfusion parameters were obtained and analyzed.ResultsClinicopathological features (pathological grade and microvascular invasion) were significantly different between the high and low Ki-67 expression groups (p = 0.029 and p = 0.020, respectively). In the high Ki-67 expression group, the peak energy (PE) in the arterial phase and fall time (FT) were significantly different between the HCC lesions and distal liver parenchyma (p = 0.016 and p = 0.025, respectively). PE in the Kupffer phase was significantly different between the HCC lesions and the distal liver parenchyma in the low Ki-67 expression group (p = 0.029). The difference in PE in the Kupffer phase between HCC lesions and distal liver parenchyma was significantly different between the high and low Ki-67 expression groups (p = 0.045). The difference in PE in the Kupffer phase between HCC lesions and distal liver parenchyma < − 4.0 × 107 a.u. may contribute to a more accurate diagnosis of the high Ki-67 expression group, and the sensitivity and specificity were 82.9% and 38.7%, respectively.ConclusionsThe DCE-US parameters have potential as biomarkers for predicting Ki-67 expression in patients with HCC.

Expression of Ki67 and p53 and their Relationship with the Survival Time of High-Dose Hypofractionated Radiotherapy in Pancreatic Cancer

<h3>Purpose/Objective(s)</h3> To analyze the expression of Ki67 and p53 in pancreatic cancer and their relationship with the survival time of high-dose hypofractionated radiotherapy. <h3>Materials/Methods</h3> The biopsies of 55 patients with pancreatic cancer were collected retrospectively before receiving high-dose hypofractionated radiotherapy. Immunohistochemical SP method was used to detect the expression of Ki67 and p53 in pancreatic cancer. Log-rank test was used to compare the difference of survival time between different expression levels. Cox model was analyzed by multivariate analysis. <h3>Results</h3> The expression rates of Ki67 and p53 protein in puncture tissues were 41.8% and 47.3%, respectively. Univariate survival analysis showed that the survival time of Ki67 and p53 negative expression group was significantly longer than that of positive group (P < 0.05). Multivariate analysis showed that Ki67, p53 and distant metastasis were independent prognostic factors of pancreatic cancer patients receiving high-dose hypofractionated radiotherapy. <h3>Conclusion</h3> The expression level of Ki67 and p53 protein in pathological tissue before treatment is an important index to predict the survival time of high-dose hypofractionated radiotherapy for pancreatic cancer.

150P Assessment of high Ki67 (≥20%) ER+HER2- breast cancer with a 21-gene multigene assay

Ki67 immunohistochemistry (IHC) with a cut-off of 20% by MIB-1 PharmDx assay has been approved as a companion diagnostic for adjuvant abemaciclib in high-risk ER+HER2- breast cancer. We addressed the genomic risk profile of high Ki67 (≥20%) ER+HER2- breast cancer using a 21-gene multigene assay (Oncotype DX test). In addition, we investigated survival outcomes and identified factors associated with low genomic risk in the high Ki67 group.

Correlation of the Ki67 Working Group prognostic risk categories with the Oncotype DX Recurrence Score in early breast cancer.

The relationship between Ki67 assessed by immunohistochemistry (IHC) and the Oncotype DX Recurrence Score (RS) is unclear. The objective of this study was to determine the correlation between the 21-gene RS and IHC-measured Ki67 with the prognostic classification groups recommended by the International Ki67 Working Group (IKWG). The authors performed a retrospective chart review of women who had hormone receptor (HR)-positive, human epidermal growth factor receptor 2-negative early breast cancer with zero to three positive lymph nodes and both Ki67 and the 21-gene RS performed at their institution from 2013 to 2021. Patients were categorized into low (≤5%), intermediate (6%-29%), and high Ki67 groups (≥30%) according to IKWG recommendations. Overall agreement and risk-stratified agreement between Ki67 and RS were assessed with the proportion of agreement and the κ statistic. The study included 525 patients with HR-positive breast cancer. Among the 49% of patients with intermediate Ki67 values of 6%-29%, the distribution of low (0-10), intermediate (11-25), and high RS (26-100) was 19%, 66%, and 15%, respectively. There was slight agreement (κ=0.01-0.20) between Ki67 and RS (κ=0.027) in the overall population, although this was not significant (p=.1985). There was fair agreement (κ=0.21-0.40) between high Ki67 and RS values (κ=0.280; p < .0001). A higher progesterone receptor percentage was associated with lower RS values (p > .0001) but not lower Ki67 values. A positive nodal status and a larger tumor size were associated with higher Ki67 values (p=.0059 and p < .0001) but not with RS. In this group of patients selected to have a 21-gene RS, there was no significant correlation between Ki67 and RS in the overall population, and there was fair agreement between high Ki67 and high RS values. In patients with early-stage, hormone receptor-positive breast cancer, decisions on adjuvant chemotherapy are based on certain biological features of the cancer and genomic assays such as the Oncotype DX Recurrence Score (RS). The goal of this study was to determine the correlation between Ki67, a marker of proliferation, and the Oncotype DX RS, a 21-gene assay demonstrated to be predictive of an adjuvant chemotherapy benefit in patients with early-stage breast cancer. In 525 patients, the authors did not find a significant correlation between Ki67 and RS.

Correlation of Ki67 working group prognostic risk categories with oncotype DX recurrence score (RS) in early breast cancer (EBC).

553 Background: The 21-gene RS (Oncotype DX) provides prognostic information for distant recurrence risk and is predictive of adjuvant chemotherapy benefit in hormone receptor (HR)-positive, HER-2 negative EBC. Ki67 protein expression is a proliferation marker that is determined by immunohistochemistry (IHC). The International Ki67 Working Group (IKWG) has provided guidelines for clinical use of Ki67 for prognostic classification (PMID: 33369635). The objectives of this study were to determine the correlation between IHC-measured Ki67 with the 21-gene RS, and evaluate their association with other anatomic and biologic tumor features. Methods: We performed a retrospective chart review of women with HR-positive, HER-2 negative EBC with 0-3 positive lymph nodes who had both Ki67 (via IHC using MIB-1 antibody on surgical specimen at our institutional pathology CLIA laboratory) and 21-gene RS between 2013 to 2021. Patients were categorized into Ki67 low (≤ 5%), intermediate (6-29%), and high (≥30%) based on IKWG recommendations. Overall and risk stratified agreement between Ki67 and RS were assessed using the proportion of agreement and Kappa statistic. Linear regression was used to test for associations between tumor features of ER%, PR%, and tumor size and log transformed Ki67 and RS. A t-test was used to compare average log transformed Ki67 and RS by tumor differentiation and nodal status. Results: We identified 461 patients with HR-positive BC of whom 26.7% were ≤ 50 years at diagnosis, 30% pre-menopausal and 10% node-positive. Overall, 29% (n = 137) of patients had low Ki67, 49% (n = 227) intermediate, and 21% (n = 97) high Ki67. 18% (n = 85) had RS 0-10, 67% (n = 311) had RS 11-25 and 14% (n = 65) had RS ≥ 26. There was no significant agreement (kappa &lt; 0) between Ki67 and RS (Kappa = -0.0035, p = 0.5406) in the overall population and fair agreement (kappa 0.21-0.40) between high Ki67 and RS (Kappa = 0.2510, p &lt; 0.0001). Higher ER% was significantly associated with lower RS (p &lt; 0.0001) and lower Ki67 (p = 0.0042). High tumor grade was associated with higher RS and higher Ki67 (p &lt; 0.0001). Higher PR% was associated with lower RS (p &gt; 0.0001) but not lower Ki67. Positive nodal status and larger tumor size were associated with higher Ki67 (p = 0.0081, p &lt; 0.0001) but not RS. Among the 49% of patients with intermediate Ki67 of 6-29%, the distribution of low, intermediate, and high RS was 24%, 65%, and 11%, respectively. Conclusions: In this group of patients selected to have a 21-gene RS, there was no correlation between Ki67 and RS in the overall population, and fair agreement between high Ki67 and high RS. Among the approximately one-half with an intermediate Ki67 of 6-29%, 89% would be spared chemotherapy based on a low-intermediate RS. In patients with high Ki67, 68% might be spared chemotherapy based on the RS. In the low Ki67 group, 6% had a high RS. Ki67 has limited utility in identifying patients with high or low RS.

Breast Cancer Subtypes and Quantitative Magnetic Resonance Imaging: A Systemic Review.

Magnetic resonance imaging (MRI) is the most sensitive imaging modality for breast cancer detection. This systematic review investigated the role of quantitative MRI features in classifying molecular subtypes of breast cancer. We performed a literature search of articles published on the application of quantitative MRI features in invasive breast cancer molecular subtype classification in PubMed from 1 January 2002 to 30 September 2021. Of the 1275 studies identified, 106 studies with a total of 12,989 patients fulfilled the inclusion criteria. Bias was assessed based using the Quality Assessment of Diagnostic Studies. All studies were case-controlled and research-based. Most studies assessed quantitative MRI features using dynamic contrast-enhanced (DCE) kinetic features and apparent diffusion coefficient (ADC) values. We present a summary of the quantitative MRI features and their correlations with breast cancer subtypes. In DCE studies, conflicting results have been reported; therefore, we performed a meta-analysis. Significant differences in the time intensity curve patterns were observed between receptor statuses. In 10 studies, including a total of 1276 lesions, the pooled difference in proportions of type Ⅲ curves (wash-out) between oestrogen receptor-positive and -negative cancers was not significant (95% confidence interval (CI): [−0.10, 0.03]). In nine studies, including a total of 1070 lesions, the pooled difference in proportions of type 3 curves between human epidermal growth factor receptor 2-positive and -negative cancers was significant (95% CI: [0.01, 0.14]). In six studies including a total of 622 lesions, the pooled difference in proportions of type 3 curves between the high and low Ki-67 groups was significant (95% CI: [0.17, 0.44]). However, the type 3 curve itself is a nonspecific finding in breast cancer. Many studies have examined the relationship between mean ADC and breast cancer subtypes; however, the ADC values overlapped significantly between subtypes. The heterogeneity of ADC using kurtosis or difference, diffusion tensor imaging parameters, and relaxation time was reported recently with promising results; however, current evidence is limited, and further studies are required to explore these potential applications.

Apparent Diffusion Coefficient Histogram Analysis for the Preoperative Evaluation of Ki-67 Expression in Pituitary Macroadenoma.

To explore the value of an apparent diffusion coefficient (ADC) histogram in predicting the Ki-67 proliferation index in pituitary macroadenomas. This retrospective study analyzed the pathological and imaging data of 102 patients with pathologically confirmed pituitary macroadenoma. Immunohistochemistry staining was used to assess Ki-67 expression in tumor tissue samples, and ahigh Ki-67 labeling index was defined as 3%. The ADC images of the maximum slice of tumors were selected and the region of interest (ROI) of each slice was delineated using the MaZda software (version 4.7, Technical University of Lodz, Institute of Electronics, Łódź, Poland) and analyzed by ADC histogram. Histogram characteristic parameters were compared between the high Ki-67 group (n = 42) and the low Ki-67 group (n = 60). The important parameters were further analyzed by receiver operating characteristic (ROC). The mean value, and the 1st, 10th, 50th, 90th, and 99th percentiles were found to be negatively correlated with Ki-67 expression (all P < 0.05), with correlation coefficients of -0.292, -0.352, -0.344, -0.289, -0.253 and -0.267, respectively. The mean ADC and the 1st, 10th, 50th, 90th, and 99th quantiles extracted from the histogram were significantly lower in the high Ki-67 group than in the low Ki-67 group (all P < 0.05). The area under the ROC curve was 0.699-0.720; however, there were no significant between-group differences in variance, skewness and kurtosis (all P > 0.05). An ADC histogram can be areliable tool to predict the Ki-67 proliferation status in patients with pituitary macroadenomas.

Enhanced computed tomography features predict pancreatic neuroendocrine neoplasm with Ki-67 index less than 5%

BackgroundSeveral studies have suggested that patients with pancreatic neuroendocrine neoplasm (pNEN) with the Ki-67 index of < 5% are more likely to show better prognosis after clinical intervention. Moreover, the Ki-67 index at 5% has also been suggested as a potential threshold by the 2016 European Neuroendocrine Tumor Society guidelines. ObjectiveBased on preoperative enhanced computed tomography (CT), this study aimed to investigate imaging characteristics eligible to discriminate the ≤ 5% Ki-67 group from the > 5% Ki-67 group of patients with nonmetastatic pNEN. MethodsPatients with pathologically diagnosed pNEN and preoperative multiphase CT were enrolled. Their Ki-67 index was calculated and grouped according to the 5% cutoff value. The following CT imaging characteristics and some serum biomarkers were assessed between the two groups: the diameter, location, tumor margin, calcification, pancreatic atrophy, distal pancreatic duct dilation, vessel involvement, and enhancement pattern characteristics of both arterial phase (AP) and portal vein phase (PVP). ResultsA total of 142 patients with pNEN were enrolled in this study, comprising 104 in the low (Ki-67, 1%–5%) and 38 in the high index group (Ki-67, >5%). Alpha fetoprotein and cancer antigen 125 were significantly different between the two groups (P-values, 0.030 and 0.049, respectively). The diameter (P < 0.0001), margin (P = 0.003), distal main ductal dilation (P = 0.021), vessel involvement (P = 0.002), AP hypoenhancement (P < 0.0001), PVP hypoenhancement (P = 0.003), AP ratio (P = 0.0001), and PVP ratio (P = 0.0003) were significantly different between the low and high index groups. The area under the curve of the multivariate logistic regression model was 0.853. ConclusionNonmetastatic pNENs with larger diameter, ill-defined margin, distal main ductal dilation, and tumor hypoenhancement in AP in preoperative enhanced CT tend to have a Ki-67 index of > 5%.The results of this study provide an alternative method to clinicians to decide whether surgery is appropriate.

The Ki-67 Proliferation Index-Related Nomogram to Predict the Response of First-Line Tyrosine Kinase Inhibitors or Chemotherapy in Non-small Cell Lung Cancer Patients With Epidermal Growth Factor Receptor-Mutant Status.

Background: The correlation between Ki-67 and epidermal growth factor receptor (EGFR)- or Kristen rat sarcoma viral oncogene homolog (KRAS)-mutant status in advanced or postoperative-recurrent non-small cell lung cancer (NSCLC) has fewer studies reported, and the prognostic role of Ki-67 with first-line EGFR-tyrosine kinase inhibitors (TKIs) or chemotherapy remains controversial.Methods: A total of 295 patients were tested for EGFR-mutant status in advanced or postoperative-recurrent NSCLC and received first-line EGFR-TKIs or chemotherapy for treatment. Ki-67 expression was retrospectively analyzed by immunohistochemistry. The Kaplan-Meier method was used to calculate survival rates. The multivariate Cox proportional hazards model was used to generate a nomogram. The established nomogram was validated using the calibration plots.Results: The expression levels of Ki-67 were divided into low (<60%, n = 186) and high (≥60%, n = 109) groups, based on the receiver operating characteristic curve. The expression levels of Ki-67 were found to be higher in patients with KRAS mutations when compared to KRAS wildtype, and EGFR wildtype was higher than EGFR mutations. The median overall survival (OS) of the low Ki-67 expression group was significantly longer than that of the high Ki-67 group, no matter in all NSCLC, EGFR mutations, EGFR wildtype, KRAS-mutant status, EGFR-TKIs, or chemotherapy of patients (P < 0.05). Subgroup analysis showed that the KRAS wildtype or EGFR mutations combine with low Ki-67 expression group had the longest median OS than KRAS mutations or EGFR wildtype combine with Ki-67 high expression group (P < 0.05). In the training cohort, the multivariate Cox analysis identified age, serum lactate dehydrogenase (LDH), serum Cyfra211, EGFR mutations, and Ki-67 as independent prognostic factors, and a nomogram was developed based on these covariates. The calibration curve for predicting the 12-, 24-, and 30-month OS showed an optimal agreement between the predicted and actual observed outcomes.Conclusions: The Ki-67 expression-based nomogram can well predict the efficacy of first-line therapy in NSCLC patients with EGFR- or KRAS-mutant status, high expression levels of Ki-67 correlated with a poor prognosis.

Vestibular Schwannomas in Young Patients: A 12-Year Experience in a Single Center

This study evaluated the characteristics of vestibular schwannomas (VS) in young patients, including clinical features, treatment, prognosis, and histopathologic characteristics. We retrospectively reviewed medical records and follow-up data for 36 pediatric patients <21 years of age who were surgically treated for VS in the Chinese PLA General Hospital between 2008 and2019. Mean patient age was 17.4 years. Mean tumor size was 2.8 cm. Hearing loss (n= 32, 88.9%) and tinnitus (n= 20, 55.6%) were the most common symptoms. Ten patients (27.8%) had impaired facial nerve function after surgery. Gross total resection (GTR) was achieved in 26 cases (72.2%). The median tumor Ki-67 level was 5%. Tumor size was related to incomplete tumor resection (odds ratio, 0.2; 95% confidence interval, 0.1-0.9) and postoperative facial nerve dysfunction (odds ratio, 24.9; 95% confidence interval, 1.2-539.1). Tumor size was nonlinearly associated with prognosis and 2.2 cm corresponded to the inflection point at which the probability of tumor remnant and postoperative facial nerve dysfunction significantly increased. The GTR and low Ki-67 groups achieved better 3-year tumor control rate. Histopathologic findings confirmed the presence of cellular schwannoma subtype in young patients. Tumor size is an important factor affecting the prognosis of VS in young patients. For large VS, surgical treatment should be the first choice, rather than wait-and-scan. VS in young patients shows high tumor proliferation and a tendency to relapse. The cellular schwannoma subtype requires special attention; an accurate histopathologic diagnosis is necessary for young patients with VS, and a closer follow-up strategy should be adopted for cellular VS.

On the Additional Information Provided by 3T-MRI ADC in Predicting Tumor Cellularity and Microscopic Behavior

Simple SummaryBreast cancer is the most common cancer in women worldwide. Increasing knowledge of the microscopic behavior of tumors has allowed for personalized and increasingly effective therapies. Biopsy is the first step in the histological evaluation of breast cancer. However, biopsy may only be partially representative of the entire tumor. The only currently recognized independent histological prognostic factor is grading, an expression of replicative cellular behavior. However, other factors such as the Ki-67 proliferation index and tumor cellularity provide additional information on tumor aggressiveness. MRI is the imaging technique routinely used in the loco-regional tumor staging phase. Currently, the MRI protocol includes DWI sequences. DWI is an expression of the restriction of water molecules and can be quantified through ADC values. In our work, entitled “On the additional information provided by 3T-MRI ADC in predicting tumor cellularity and microscopic behavior”, we aim to demonstrate how ADC can significantly correlate with these histological factors, in particular with the cellularity obtained in the definitive histological sample compared to the biopsy sample; ADC values may therefore offer a valuable support for biological evaluation in the pre-surgical phase.Background: to evaluate whether Apparent Diffusion Coefficient (ADC) values of invasive breast cancer, provided by 3T Diffusion Weighted-Images (DWI), may represent a non-invasive predictor of pathophysiologic tumor aggressiveness. Methods: 100 Patients with histologically proven invasive breast cancers who underwent a 3T-MRI examination were included in the study. All MRI examinations included dynamic contrast-enhanced and DWI/ADC sequences. ADC value were calculated for each lesion. Tumor grade was determined according to the Nottingham Grading System, and immuno-histochemical analysis was performed to assess molecular receptors, cellularity rate, on both biopsy and surgical specimens, and proliferation rate (Ki-67 index). Spearman’s Rho test was used to correlate ADC values with histological (grading, Ki-67 index and cellularity) and MRI features. ADC values were compared among the different grading (G1, G2, G3), Ki-67 (<20% and >20%) and cellularity groups (<50%, 50–70% and >70%), using Mann–Whitney and Kruskal-Wallis tests. ROC curves were performed to demonstrate the accuracy of the ADC values in predicting the grading, Ki-67 index and cellularity groups. Results: ADC values correlated significantly with grading, ER receptor status, Ki-67 index and cellularity rates. ADC values were significantly higher for G1 compared with G2 and for G1 compared with G3 and for Ki-67 < 20% than Ki-67 > 20%. The Kruskal-Wallis test showed that ADC values were significantly different among the three grading groups, the three biopsy cellularity groups and the three surgical cellularity groups. The best ROC curves were obtained for the G3 group (AUC of 0.720), for G2 + G3 (AUC of 0.835), for Ki-67 > 20% (AUC of 0.679) and for surgical cellularity rate > 70% (AUC of 0.805). Conclusions: 3T-DWI ADC is a direct predictor of cellular aggressiveness and proliferation in invasive breast carcinoma, and can be used as a supporting non-invasive factor to characterize macroscopic lesion behavior especially before surgery.

Ki67 Index Changes and Tumor-Infiltrating Lymphocyte Levels Impact the Prognosis of Triple-Negative Breast Cancer Patients With Residual Disease After Neoadjuvant Chemotherapy.

PurposeThe aim of this study was to assess the prognostic influence of Ki67 index changes in patients with primary triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NAC), and to evaluate whether the combination of Ki67 index changes and residual disease (RD) tumor-infiltrating lymphocytes (TILs) provides additional prognostic information for this group.Materials and MethodsData from 109 patients with primary TNBC and RD after NAC were analyzed retrospectively. Ki67 changes and RD TIL levels were investigated for associations with recurrence-free survival (RFS) and overall survival (OS) using Kaplan–Meier and Cox analyses.ResultsKi67 index decreased after NAC in 53 patients (48.6%) and high RD TIL levels (≥30%) were observed in 54 patients (49.5%). In multivariate Cox analyses, no Ki67 decrease status and low RD TIL levels were significantly associated with reduced RFS (hazard ratio (HR): 2.038, 95% confidence interval (CI): 1.135–3.658, P = 0.017; HR: 2.493, 95% CI: 1.335–4.653, P = 0.004), and OS (HR: 2.187, 95% CI: 1.173–4.077, P = 0.014; HR: 2.499, 95% CI: 1.285–4.858, P = 0.007), respectively. Notably, low RD TIL levels were significantly associated with reduced RFS (HR: 3.567, 95% CI: 1.475–8.624, P = 0.005) and reduced OS (HR: 3.873, 95% CI: 1.512–9.918, P = 0.005) in only the no Ki67 decrease group. The differences in 3-year RFS and OS between patients with no Ki67 decrease and low or high RD TIL levels were 24.4% vs 79.1% (P = 0.0001) and 33.1% vs 87.5% (P = 0.0001), respectively.ConclusionKi67 index changes and RD TIL levels were associated with the prognosis of patients with primary TNBC with RD after NAC. RD TIL levels had greater prognostic significance in the no Ki67 decrease group.

Correlations between apparent diffusion coefficient values and histopathologic factors in breast cancer.

Breast cancer is the most common malignancy dia-gnosed in women, and the incidence gradually increases. Magnetic resonance imaging (MRI) is become widely used to identify benign and malignant breast tumors. Objective: The aim of this study was to evaluate the relationships between apparent diffusion coefficient (ADC) values and histopathologic prognostic factors in breast cancer. Forty-nine breast carcinoma patients were included evaluated for prognostic factors, including histological type, histo-logical grade, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and molecular subtype. Minimum (ADCmin) and mean (ADCmean) ADC values were compared among prognostic factor groups by Mann-Whitney U test and Kruskal-Wallis test. Lower mean ADCmin and ADCmean values were observed for no special type (NST) than for invasive lobular carcinoma (ILC) type (0.81 ± 0.03 × 10-3 and 0.96 ± 0.03 × 10-3 mm2/s, P= 0.002 and 0.03, respectively). The mean ADCmin and ADCmean values for the high-level Ki-67 group were significantly lower than those for the low-level Ki-67 group (P = 0.001 and 0.008, respectively). No correlations were observed between ADC values and histological grades, ER, PR, HER2, and molecular subtypes. ADCmin and ADCmean values correlated with the pro-liferation marker Ki-67 and histological grade. ADC values can serve as noninvasive indicators of cell proliferation in breast cancer.

An analysis of Ki-67 expression in stage 1 invasive ductal breast carcinoma using apparent diffusion coefficient histograms.

To investigate the value of apparent diffusion coefficient (ADC) histograms in differentiating Ki-67 expression in T1 stage invasive ductal breast carcinoma (IDC). The records of 111 patients with pathologically confirmed T1 stage IDC who underwent magnetic resonance imaging prior to surgery were retrospectively reviewed. The expression of Ki-67 in tumor tissue samples from the patients was assessed using immunohistochemical (IHC) staining, with a cut-off value of 25% for high Ki-67 labeling index (LI). ADC images of the maximum lay of tumors were selected, and the region of interest (ROI) of each lay was delineated using the MaZda software and analyzed by histogram. The correlations between the histogram characteristic parameters and the Ki-67 LI were investigated. Additionally, the histogram characteristic parameters of the high Ki-67 group (n=54) and the low Ki-67 group (n=57) were statistically analyzed to determine the characteristic parameters with significant difference. Receiver operator characteristic (ROC) analyses were further performed for the significant parameters. The mean value, and the 1st, 10th, 50th, 90th, and 99th percentiles were found to be negatively correlated with the expression of Ki-67 (all P values <0.001), with a correlation coefficient of -0.624, -0.749, -0.717, -0.621, -0.500, and -0.410, respectively. In the high Ki-67 group, the mean value, and the 1st, 10th, 50th, 90th, and 99th percentiles extracted by the histogram were significantly lower (all P values <0.05) than that of the low Ki-67 group, with areas under the ROC curves ranging from 0.717-0.856. However, the variance, skewness, and kurtosis did not differ between the two groups (all P values >0.05). Histogram-derived parameters for ADC images can serve as a reliable tool in the prediction of Ki-67 proliferation status in patients with T1 stage IDC. Among the significant ADC histogram values, the 1st and 10th percentiles showed the best predictive values.

Three-dimensional pulsed continuous arterial spin labeling and intravoxel incoherent motion imaging of nasopharyngeal carcinoma: correlations with Ki-67 proliferation status.

Recurrence and distant metastasis are still the main problems affecting the long-term prognosis of nasopharyngeal carcinoma (NPC) patients, and may be related to the Ki-67 proliferation status. We therefore explored the potential correlation between Ki-67 proliferation status in NPC with the parameters derived from two imaging techniques: three-dimensional pulsed continuous arterial spin labeling (3D pCASL) and intravoxel incoherent motion (IVIM). Thirty-six patients with pathologically confirmed NPC were included, and the Ki-67 labeling index (LI) was measured by immunohistochemistry. All patients underwent plain and contrast-enhanced magnetic resonance imaging (MRI), IVIM, and 3D pCASL examination. The mean, maximum, and minimum of blood flow (BF), minimum of apparent diffusion coefficient (ADC), pure diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) parameters were all measured, and Spearman's correlation analysis was performed to evaluate the relationships between these parameters and the Ki-67 LI. According to the Ki-67 values, the patients were divided into two groups: high (>50%) and low (≤50%). The rank-sum test (Mann-Whitney U test) was then used to compare the differences in quantitative parameters between the high and low Ki-67 groups. Ki-67 LI was positively correlated with BFmean and BFmax (r=0.415 and 0.425). D*mean and D*min did have positive correlation with Ki-67, but this was not significant (P=0.082 and 0.072). BFmax was significantly different between the high and low Ki-67 groups (P=0.028). 3D pCASL and IVIM are noninvasive functional MR perfusion imaging techniques that can evaluate perfusion information and perfusion parameters. Our study suggests that 3D pCASL is more effective than IVIM for assessing the proliferation status of NPC, which is beneficial for evaluating the prognosis of patients. Furthermore, BFmax is the best biomarker for distinguishing high from low Ki-67 levels.

Correlation analysis of Ki67, Ck19 with clinicopathological features and apparent diffusion coefficient value of hepatocellular carcinoma

Objective: To investigate the expression of cell proliferating nuclear antigen (Ki67) and cytokeratin 19 (Ck19) in hepatocellular carcinoma (HCC), and correlation with the clinicopathological features and apparent diffusion coefficient (ADC) value of hepatocellular carcinoma. Methods: The data of 203 newly diagnosed HCC patients in the Affiliated Cancer Hospital of Zhengzhou University from January 2014 to October 2019 were retrospectively collected, and the expression of Ki67 and Ck19 and ADC values in all patients were analyzed. The relationship between Ki67 and Ck19 and the clinical pathological characteristics of the patient, and calculate the difference and correlation with the ADC value was analyzed. Results: There were statistically significant differences in tumor vascular tumor thrombus, alpha-fetoprotein (AFP), postoperative tumor recurrence, lymph node metastasis, and HCC differentiation between Ki67 positive and negative groups (χ²=5.156, 12.741, 29.925, 3.963, 77.408, all P<0.05),and negatively correlated with ADC value (r=-0.214, P=0.002). The average ADC value of HCC in the low Ki67 group was significantly higher than that of the high Ki67 group (1 089±280 vs 1 009±212, P<0.05). There were statistically significant differences in tumor vascular tumor thrombus, AFP, postoperative tumor recurrence, and lymph node metastasis between Ck19 positive and negative groups (χ²=9.058, 27.034, 4.053, 14.187, all P<0.05), but not correlated with ADC value (r=0.062, P=0.380). The expression differences of Ki67 and Ck19 in different HCC recurrence time groups were statistically significant (P<0.05). Conclusion: The positive expression of Ki67 and Ck19 in HCC was associated with the prognosis and recurrence of HCC. CK19 was not correlated with the ADC value, while Ki67 was negatively correlated with the ADC value, indicating that ADC value could provide certain imaging information for the biological characteristics of preoperative HCC.