Low Ki-67 Expression Research Articles

Interpretable machine learning model based on CT semantic features and radiomics features to preoperatively predict Ki-67 expression in gastrointestinal stromal tumors

To develop and validate a machine learning (ML) model which combined computed tomography (CT) semantic and radiomics features to preoperatively predict Ki-67 expression in gastrointestinal stromal tumors (GISTs) patients. We retrospectively collected the clinical, imaging and pathological data of 149 GISTs patients. We randomly assigned the patients in a ratio of 7:3 to a training set (104 cases) and a validation (45 cases) set. We divided the patients into low and high Ki-67 expression group according to postoperative pathology. CT semantic features were analyzed from preoperative enhancement CT images and radiomics features were extracted from venous phase-enhanced images. We used intraclass correlation coefficient, maximal relevance and minimal redundancy and least absolute shrinkage and selection operator method to screen radiomics features and build radiomics label. 6 ML models were used for model construction. Receiver operating characteristic curves were used to evaluate the predictive efficiency of ML models. SHAP analysis was used to explain the contribution of different variables and their risk threshold. AUC of radscores in predicting Ki-67 expression of GIST patients were 0.749 and 0.729 in training and validation set. Among the 6 ML models, SVM exhibited best prediction accuracy. AUC of SVM model in predicting Ki-67 expression of GIST patients were 0.840, 0.767 and 0.832 in training, validation and test set. SHAP analysis showed that radscores and tumor diameter had highly positive contribution to the model. Therefore, the interpretable SVM model can predict Ki-67 expression of GISTs patients individually before surgery, which can provide reliable imaging biomarkers for clinical treatment decisions.

Diffusion-weighted imaging based on intravoxel incoherent motion: correlation with molecular prognostic factors and subtypes in breast cancer.

Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI), which indicates biological tissue attributes, may be applied to accurately assess breast tumors. To analyze the IVIM parameters of different molecular prognostic factors and subtypes to find out whether there are any connections. A total of 181 patients enrolled in this retrospective study had preoperative magnetic resonance imaging (MRI) examinations, and pathologies were verified as breast cancers. Regions of interest were placed at all slices of the parameter maps (D, tissue diffusivity; ADC, apparent diffusion coefficient; f, perfusion fraction; and D*, pseudo-diffusivity maps) of IVIM and generated parameter values to be used for comparative analysis among molecular prognostic factors and subtypes. D and ADC were greater in estrogen receptor (ER)-negative, human epidermal growth factor receptor 2 (HER2)-positive, and Ki67-low expression groups (all P values < 0.05). The progesterone receptor (PR)-negative group had a higher D value (P < 0.05). f was larger in the lymph node metastasis-negative group and the PR-positive group (P = 0.012 and 0.046, respectively). Among breast cancer subtypes, D and ADC were different between the HER2-overexpression and the Luminal B (HER2-negative) subtypes (P = 0.019 and 0.028, respectively). The difference in D between the luminal and non-luminal subtypes was statistically significant (P = 0.008). The triple-negative subtype significantly differs from the other subtypes in D* and f (P = 0.012 and 0.016, respectively). IVIM-related metrics exhibited relationships with breast cancer molecular prognosis factors and subtypes.

Value of high frame rate contrast-enhanced ultrasound in predicting microvascular invasion of hepatocellular carcinoma

ObjectivesTo investigate the value of vascular morphology on high frame rate contrast-enhanced ultrasound (H-CEUS) and CEUS Li-RADS in predicting microvascular invasion (MVI), Ki-67 expression and recurrence of hepatocellular carcinoma (HCC).MethodsThis retrospective study enrolled 78 patients with single HCC diagnosed by postoperative pathology between January 1, 2021, and June 30, 2022. All patients underwent ultrasound and H-CEUS examination before operation. H-CEUS image features and CEUS Li-RADS were compared in different MVI status and Ki-67 level. Multiple logistic regression analysis was performed to select independent variables for MVI. Differences in recurrence among different H-CEUS image features, MVI status and Ki-67 level were further analyzed.ResultsTumor shape, vascular morphology, LR-M category, necrosis and AFP level were different between the MVI-positive group and MVI-negative group (p < 0.05). Vascular morphology and LR-M category were independent risk factors related to MVI (p < 0.05). Vascular morphology was also different between the high Ki-67 expression group and low Ki-67 expression group (p < 0.05). Vascular morphology, MVI status and Ki-67 expression were different between the recurrence group and no recurrence group (p < 0.05).ConclusionThe vascular morphology of HCC on H-CEUS can indicate the risk of MVI status, Ki-67 expression and recurrence, which provides a feasible imaging technique for predicting the prognosis before operation.Critical relevance statementH-CEUS shows the different vascular morphology of HCC in arterial phase and indicates the risk of MVI, Ki-67 expression and recurrence, which provides a feasible imaging technique for clinician to judge the risk of MVI pre-operation and adopt appropriate treatment.Key PointsH-CEUS can clearly show different vascular morphology of HCC in arterial phase.Vascular morphology on H-CEUS is associated with MVI status, Ki-67 expression and HCC recurrence.Preoperative MVI and Ki-67 expression prediction could help surgeons choose a more appropriate treatment plan.Graphical

Clinicopathological characteristics of mucinous breast cancer: a retrospective analysis of a 6-years study from national cancer center in Vietnam.

To evaluate clinicopathological features in women with mucinous breast cancer (MBC), distinguishing between pure (PMC) and mixed (MMC) subtype. A retrospective analysis of all 358 women with MBC treated at Vietnam National Cancer hospital from June 2015 to December 2020. PMC was defined by ≥ 90% mucinous components. We identified 358 women with MBC (245 PMC and 113 MMC) representing 2.7% of all 13,254 BC patients. The proportions of stage I, II, III and IV were 34.9%, 50.8%, 10.4% and 3.9% respectively. The rate of HER2 overexpression was 12%, and only 1.4% of patients was treated with anti-HER2. 193 patients (53.9%) had chemotherapy, including 55 patients (15.4%) treated in the neoadjuvant setting. Only 3 patients (5.5%) achieved pCR. PMC patients were older (54.4 ± 13.3 vs 51.1 ± 13.1years), had lower Ki67 expression, lower incidence of nodal metastasis (N +) (p values < 0.05). At a median follow-up of 58months, the 5-year overall survival rate of non-metastatic patients was 86.6%. Multivariate analysis showed N + to be the most significant prognostic factor (HR = 3.3; 95%CI 1.5-7.1), followed by T-stage (HR = 2.9; 95%CI 1.4-6.3), HER2 + (HR = 2.5; 95%CI 1.2-5.3) and MMC subtype (HR = 1.9; 95%CI 1.0-3.9). Poor prognostic factors of MBC include high T-stage, N-positivity, HER2 overexpression and MMC subtype. Given the low response rate to neoadjuvant CT, upfront surgery is appropriate for MBC patients.

Multimodal apparent diffusion MRI model in noninvasive evaluation of breast cancer and Ki-67 expression

BackgroundTo assess the capability of multimodal apparent diffusion (MAD) weighted magnetic resonance imaging (MRI) to distinguish between malignant and benign breast lesions, and to predict Ki-67 expression level in breast cancer.MethodsThis retrospective study was conducted with 93 patients who had postoperative pathology-confirmed breast cancer or benign breast lesions. MAD images were acquired using a 3.0 T MRI scanner with 16 b values. The MAD parameters, as flow (fF, DF), unimpeded (fluid) (fUI), hindered (fH, DH, and αH), and restricted (fR, DR), were calculated. The differences of the parameters were compared by Mann–Whitney U test between the benign/malignant lesions and high/low Ki-67 expression level. The diagnostic performance was assessed by the area under the receiver operating characteristic curve (AUC).ResultsThe fR in the malignant lesions was significantly higher than in the benign lesions (P = 0.001), whereas the fUI and DH were found to be significantly lower (P = 0.007 and P < 0.001, respectively). Compared with individual parameter in differentiating malignant from benign breast lesions, the combination parameters of MAD (fR, DH, and fUI) provided the highest AUC (0.851). Of the 73 malignant lesions, 42 (57.5%) were assessed as Ki-67 low expression and 31 (42.5%) were Ki-67 high expression. The Ki-67 high status showed lower DH, higher DF and higher αH (P < 0.05). The combination parameters of DH, DF, and αH provided the highest AUC (0.691) for evaluating Ki-67 expression level.ConclusionsMAD weighted MRI is a useful method for the breast lesions diagnostics and the preoperative prediction of Ki-67 expression level.

Establishment of human pluripotent stem cell-derived cortical neurosphere model to study pathomechanisms and chemical toxicity in Kleefstra syndrome

In the present study, we aimed to establish and characterize a mature cortical spheroid model system for Kleefstra syndrome (KS) using patient-derived iPSC. We identified key differences in the growth behavior of KS spheroids determined by reduced proliferation marked by low Ki67 and high E-cadherin expression. Conversely, in the spheroid-based neurite outgrowth assay KS outperformed the control neurite outgrowth due to higher BDNF expression. KS spheroids were highly enriched in VGLUT1/2-expressing glutamatergic and ChAT-expressing cholinergic neurons, while TH-positive catecholamine neurons were significantly underrepresented. Furthermore, high NMDAR1 expression was also detected in the KS spheroid, similarly to other patients-derived neuronal cultures, denoting high NMDAR1 expression as a general, KS-specific marker. Control and KS neuronal progenitors and neurospheres were exposed to different toxicants (paraquat, rotenone, bardoxolone, and doxorubicin), and dose-response curves were assessed after acute exposure. Differentiation stage and compound-specific differences were detected with KS neurospheres being the most sensitive to paraquat. Altogether this study describes a robust 3D model system expressing the disease-specific markers and recapitulating the characteristic pathophysiological traits. This platform is suitable for testing developing brain-adverse environmental effects interactions, drug development, and screening towards individual therapeutic strategies.

LncRNA BASP1-AS1 is a positive regulator of stemness and pluripotency in human SH-SY5Y neuroblastoma cells

Neuroblastoma is the most common extra-cranial solid tumor diagnosed mostly in children below the age of five years and comprises of about 15 % of all paediatric cancer deaths. Tumor initiating cancer stem cells (CSCs) can be targeted for better treatment approaches. BASP1-AS1 is a long non coding (Lnc) RNA that is a divergent LncRNA for its coding gene brain abundant membrane attached signal protein 1 (BASP1). We had earlier demonstrated it to be expressed in foetus derived human neural progenitor cells (hNPCs), where it was a positive regulator of BASP1 and was critical for neural differentiation. In this study, we have investigated the role of BASP1-AS1 in CSCs derived from the human neuroblastoma cell line SH-SY5Y. We cultured SH-SY5Y cells on Poly-d-Lysine coated flasks in serum free media supplemented with growth factors, which led to the enrichment of CSCs as determined by marker expression. When grown on ultra-low attachment flasks, these cells formed CSCs enriched neurospheres. We examined the effects of BASP1-AS1 siRNA mediated knockdown on CSCs enriched SH-SY5Y cells and SH-SY5Y derived neurospheres. BASP1-AS1 knockdown decreased the levels of the corresponding gene BASP1 and the rate of cell proliferation of CSCs enriched cells along with low expression of Ki67. It also reduced the mRNA levels of stem cell and pluripotency gene markers (CD133, CD44, c-KIT, SOX2, OCT4 and NANOG), as also Wnt 2 and the Wnt pathway effector β catenin. It also abrogated the formation of neurospheres in ultra-low attachment flasks. A similar effect on proliferation and stemness related properties was seen on BASP1 knockdown. BASP1-AS1 and its related pathways may provide a point of intervention for the CSCs population in neuroblastoma.

Determining Clinicopathologic Factors That Influence Treatment in Advanced Breast Cancer in Argentina After CDK4/6 Inhibitors.

The optimal treatment sequence for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) after progression on first-line cyclin-dependent kinase 4/6 inhibitor (CDKi) and endocrine therapy is unclear. Clinical and biological factors influencing treatment choices and outcomes in the second-line setting need to be elucidated. This is a retrospective analysis of a real-world cohort including patients with HR+/HER2- ABC who received CDKi and endocrine therapy in the first-line setting and progressed, requiring second-line treatment. Clinical and biological factors were analyzed to evaluate their association with daily treatment decisions and the prognostic role of progression-free survival (PFS) in the second-line setting. Two hundred thirty-five patients were included. Second-line treatments were hormone therapy (HT) based in 60% and chemotherapy based in 40% of patients. The second-line median PFS was 6.6 months, with no difference between treatment types. In multivariable analysis, postmenopausal status, lower Ki-67 expression, and non-de novo stage IV disease were associated with improved second-line (2L) PFS. Menopausal status significantly interacted with treatment type, with reduced PFS in premenopausal patients receiving HT-based treatments (4.7 v 8.7 months, P = .00045). In our study, treatment decisions reflected the current algorithm incorporated in our clinical guidelines, and prior treatment response was the most relevant factor to determine 2L treatment decision. Menopausal status interacted with the subsequent therapy efficacy in this setting. Hence, we consider that menopausal status should be routinely evaluated in the subgroup analysis of clinical trials.

Imaging evaluation focused on microstructural tissue changes using tensor-valued diffusion encoding in breast cancers after neoadjuvant chemotherapy: is it a promising way forward?

Single diffusion encoding is a widely used, noninvasive technique for probing the tissue microstructure in breast tumors. However, it does not provide detailed information about the microenvironmental complexity. This study investigated the clinical utility of tensor-valued diffusion encoding for evaluating microstructural changes in breast cancer after neoadjuvant chemotherapy (NAC). We retrospectively included patients underwent chemotherapy for histologically proven invasive breast cancer between July 2020 and June 2023 and monitored the tumor response with breast magnetic resonance imaging (MRI), including tensor-valued diffusion encoding. We reviewed pre- and post-NAC MRIs regarding chemotherapy in 23 breast cancers. Q-space trajectory imaging (QTI) parameters were estimated at each time-point, and were compared with histopathological parameters. The mean total mean kurtosis (MKT), anisotropic mean kurtosis (MKA), and microscopic fractional anisotropy (µFA) were significantly decreased on post-NAC MRI compared with pre-NAC MRI, with the large effect size (ES) in MKA and µFA (0.81±0.41 vs. 0.99±0.33, ES: 0.48, P=0.03; 0.48±0.30 vs. 0.73±0.27, ES: 0.88, P<0.001; 0.58±0.14 vs. 0.68±0.11, ES: 0.79, P=0.003; respectively). Regarding prognostic factors, tumors with high Ki-67 expression showed significantly lower pre-NAC mean diffusivity (MD) and higher pre-NAC µFA compared to tumors with low Ki-67 expression (0.98±0.09 vs. 1.25±0.20, P=0.002; and 0.72±0.07 vs. 0.57±0.10, P=0.005; respectively). And negative progesterone receptor (PR) group revealed significantly lower MKT, MKA, and isotropic mean kurtosis than positive PR group on the post-NAC MRI (0.60±0.31 vs. 1.03±0.40, P=0.008; 0.36±0.21 vs. 0.61±0.33, P=0.04; and 0.23±0.17 vs. 0.42±0.25, P=0.046; respectively). QTI parameters reflected the microstructural changes in breast cancer treated with NAC and can be used as noninvasive imaging biomarkers correlated with prognostic factors.

Prediction of disease-free survival using strain elastography and diffuse optical tomography in patients with T1 breast cancer: a 10-year follow-up study

BackgroundEarly-stage breast cancer (BC) presents a certain risk of recurrence, leading to variable prognoses and complicating individualized management. Yet, preoperative noninvasive tools for accurate prediction of disease-free survival (DFS) are lacking. This study assessed the potential of strain elastography (SE) and diffuse optical tomography (DOT) for non-invasive preoperative prediction of recurrence in T1 BC and developed a prediction model for estimating the probability of DFS.MethodsA total of 565 eligible patients with T1 invasive BC were enrolled prospectively and followed to investigate the recurrence. The associations between imaging features and DFS were evaluated and a best-prediction model for DFS was developed and validated.ResultsDuring the median follow-up period of 10.8 years, 77 patients (13.6%) developed recurrences. The fully adjusted Cox proportional hazards model showed a significant trend between an increasing strain ratio (SR) (P < 0.001 for trend) and the total hemoglobin concentration (TTHC) (P = 0.001 for trend) and DFS. In the subgroup analysis, an intensified association between SR and DFS was observed among women who were progesterone receptor (PR)-positive, lower Ki-67 expression, HER2 negative, and without adjuvant chemotherapy and without Herceptin treatment (all P < 0.05 for interaction). Significant interactions between TTHC status and the lymphovascular invasion, estrogen receptor (ER) status, PR status, HER2 status, and Herceptin treatment were found for DFS(P < 0.05).The imaging–clinical combined model (TTHC + SR + clinicopathological variables) proved to be the best prediction model (AUC = 0.829, 95% CI = 0.786–0.872) and was identified as a potential risk stratification tool to discriminate the risk probability of recurrence.ConclusionThe combined imaging-clinical model we developed outperformed traditional clinical prognostic indicators, providing a non-invasive, reliable tool for preoperative DFS risk stratification and personalized therapeutic strategies in T1 BC. These findings underscore the importance of integrating advanced imaging techniques into clinical practice and offer support for future research to validate and expand on these predictive methodologies.

Self-enhanced PTX@HSA-HA loaded functionalized injectable hydrogel for effective local chemo-photothermal therapy in breast cancer

Breast cancer is a malignant tumor that poses a significant threat to women's health and single therapy fails to play a good oncological therapeutic effect. Synergistic treatment with multiple strategies may make up for the deficiencies and has gained widespread attention. In this study, sulfhydryl-modified hyaluronic acid (HA-SH) was covalently crosslinked with polydopamine (PDA) via a Michael addition reaction to develop an injectable hydrogel, in which PDA can be used not only as a matrix but also as a photothermal agent. After HSA and paclitaxel were spontaneously organized into nanoparticles via hydrophobic interaction, hyaluronic acid with low molecular weight was covalently linked to HSA, thus conferring effectively delivery. This photothermal injectable hydrogel incorporates PTX@HSA-HA nanoparticles, thereby initiating a thermochemotherapeutic response to target malignancy. Our results demonstrated that this injectable hydrogel possesses consistent drug delivery capability in a murine breast cancer model, collaborating with photothermal therapy to effectively suppress tumor growth, represented by low expression of Ki-67 and increasing apoptosis. Photothermal therapy (PTT) can effectively stimulate immune response by increasing IL-6 and TNF-α. Notably, the treatment did not elicit any indications of toxicity. This injectable hydrogel holds significant promise as a multifaceted therapeutic agent that integrates photothermal and chemotherapeutic modalities.

Prognostic heterogeneity of Ki67 in non-small cell lung cancer: A comprehensive reappraisal on immunohistochemistry and transcriptional data.

In the present study, the debatable prognostic value of Ki67 in patients with non-small cell lung cancer (NSCLC) was attributed to the heterogeneity between lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC). Based on meta-analyses of 29 studies, a retrospective immunohistochemical cohort of 1479 patients from our center, eight transcriptional datasets and a single-cell datasets with 40 patients, we found that high Ki67 expression suggests a poor outcome in LUAD, but conversely, low Ki67 expression indicates worse prognosis in LUSC. Furthermore, low proliferation in LUSC is associated with higher metastatic capacity, which is related to the stronger epithelial-mesenchymal transition potential, immunosuppressive microenvironment and angiogenesis. Finally, nomogram model incorporating clinical risk factors and Ki67 expression outperformed the basic clinical model for the accurate prognostic prediction of LUSC. With the largest prognostic assessment of Ki67 from protein to mRNA level, our study highlights that Ki67 also has an important prognostic value in NSCLC, but separate evaluation of LUAD and LUSC is necessary to provide more valuable information for clinical decision-making in NSCLC.

Loss of CFTR Reverses Senescence Hallmarks in SARS-CoV-2 Infected Bronchial Epithelial Cells.

SARS-CoV-2 infection has been recently shown to induce cellular senescence in vivo. A senescence-like phenotype has been reported in cystic fibrosis (CF) cellular models. Since the previously published data highlighted a low impact of SARS-CoV-2 on CFTR-defective cells, here we aimed to investigate the senescence hallmarks in SARS-CoV-2 infection in the context of a loss of CFTR expression/function. We infected WT and CFTR KO 16HBE14o-cells with SARS-CoV-2 and analyzed both the p21 and Ki67 expression using immunohistochemistry and viral and p21 gene expression using real-time PCR. Prior to SARS-CoV-2 infection, CFTR KO cells displayed a higher p21 and lower Ki67 expression than WT cells. We detected lipid accumulation in CFTR KO cells, identified as lipolysosomes and residual bodies at the subcellular/ultrastructure level. After SARS-CoV-2 infection, the situation reversed, with low p21 and high Ki67 expression, as well as reduced viral gene expression in CFTR KO cells. Thus, the activation of cellular senescence pathways in CFTR-defective cells was reversed by SARS-CoV-2 infection while they were activated in CFTR WT cells. These data uncover a different response of CF and non-CF bronchial epithelial cell models to SARS-CoV-2 infection and contribute to uncovering the molecular mechanisms behind the reduced clinical impact of COVID-19 in CF patients.

The correlation between Ki 67 and Oncotype Dx on HR+, HER2- early breast cancer management: Insights of molecular testing.

e12546 Background: Elevated Ki-67 expression serves as an indicator of tumoral proliferation in breast cancer (BC) and is used in Ecuador for survival estimation, recurrence risk assessment, and guiding chemotherapy decisions. The Oncotype DX Breast Recurrence Score (ODX RS) is a validated 21-gene assay for hormone receptor-positive, HER2-negative invasive BC. It predicts chemotherapy benefits and the risk of distant recurrence over 10 years and is a mortality indicator. ODX RS has the potential to reduce the need for chemotherapy, alleviate financial burdens, and enhance clinical outcomes. Despite conflicting evidence on the significance of Ki-67 in the ODX RS, there is a lack of exploration within Latin populations. This study aims to compare the correlation of immunohistochemical (IHC) measured Ki-67 to the ODX RS in the Ecuadorian population. Methods: A retrospective analysis included women with early BC who underwent ODX RS testing in Ecuador from May 2020 to January 2023. Inclusion criteria: early BC (T1-T3/N0-N1a); IHC estrogen receptor (ER) positive; HER2 negative; and availability of tumor size, grade, lymph node status, and Ki67 proliferation index data. Exclusion criteria: patients with recurrent BC, incomplete pathology, or lacking IHC data. Patients were categorized into low (≤5%), intermediate (6%–29%), and high Ki67 expression groups (≥30%). Using the statistical software SPSS, the correlation between ODX scores and Ki-67 expression was analyzed using Pearson’s correlation coefficient. For risk stratification groups, Spearman's correlation was employed. Results: Among 77 patients undergoing Oncotype DX testing, 64 (with a mean age of 55) met the inclusion criteria. Eighty-six percent of cases were invasive ductal carcinomas (IDC). Seventeen percent exhibited low Ki-67 expression, 61% intermediate, and 20% high. No statistically significant correlation was found between IHC Ki-67 expression and ODX RS (r=0.051; p=0.69), neither when stratified by categories (r=0.086; p=0.50). A subanalysis based on risk categories showed 82% correspondence in the low Ki-67 group, 18% in the intermediate group, and 31% in the high Ki-67 group. No significant correlation was observed when stratified by histological types (invasive ductal carcinoma and invasive lobular carcinoma), nor by sample origin (core biopsy, excisional biopsy). Conclusions: There was no correlation between IHC Ki-67 expression and ODX risk scores in this study involving Ecuadorian patients. Our findings emphasize that IHC Ki-67 expression should not be the sole determinant for guiding therapeutic decisions and predicting recurrence in early breast cancer.[Table: see text]

The value of the malignant subregion-based texture analysis in predicting the Ki-67 status in breast cancer.

To evaluate the value of the malignant subregion-based texture analysis in predicting Ki-67 status in breast cancer. The dynamic contrast-enhanced magnetic resonance imaging data of 119 histopathologically confirmed breast cancer patients (81 patients with high Ki-67 expression status) from January 2018 to February 2023 in our hospital were retrospectively collected. According to the enhancement curve of each voxel within the tumor, three subregions were divided: washout subregion, plateau subregion, and persistent subregion. The washout subregion and the plateau subregion were merged as the malignant subregion. The texture features of the malignant subregion were extracted using Pyradiomics software for texture analysis. The differences in texture features were compared between the low and high Ki-67 expression cohorts and then the receiver operating characteristic (ROC) curve analysis to evaluate the predictive performance of texture features on Ki-67 expression. Finally, a support vector machine (SVM) classifier was constructed based on differential features to predict the expression level of Ki-67, the performance of the classifier was evaluated using ROC analysis and confirmed using 10-fold cross-validation. Through comparative analysis, 51 features exhibited significant differences between the low and high Ki-67 expression cohorts. Following feature reduction, 5 features were selected to build the SVM classifier, which achieved an area under the ROC curve (AUC) of 0.77 (0.68-0.87) for predicting the Ki-67 expression status. The accuracy, sensitivity, and specificity were 0.76, 0.80, and 0.68, respectively. The average AUC from the 10-fold cross-validation was 0.72 ± 0.14. The texture features of the malignant subregion in breast cancer were potential biomarkers for predicting Ki-67 expression level in breast cancer, which might be used to precisely diagnose and guide the treatment of breast cancer.

Vitrification of feline ovarian tissue: Comparison of protocols based on equilibration time and temperature

Global contraction of biodiversity pushed most members of Felidae into threatened or endangered list except the domestic cat (Felis catus) thence preferred as the best model for conservation studies. One of the emerging conservation strategies is vitrification of ovarian tissue which is field-friendly but not yet standardized. Thus, our main goal was to establish a suitable vitrification protocol for feline ovarian tissue in field condition. Feline ovarian tissue fragments were punched with biopsy punch (1.5 mm diameter) and divided into 4 groups. Group 1 was fresh control (Fr), while the other three were exposed to 3 vitrification protocols (VIT_CT, VIT_RT1 and VIT_RT2). VIT_CT involved two step equilibrations in solutions containing dimethyl sulfoxide (DMSO) and ethylene glycol (EG) for 10 min each at 4 °C. VIT_RT1 involved three step equilibration in solutions containing DMSO, EG, polyvinylpyrrolidone and sucrose for 14 min in total at room temperature, while in VIT_RT2 all conditions remained the same as in VIT_RT1 except equilibration timing which was reduced by half. After vitrification and warming, fragments were morphologically evaluated and then cultured for six days. Subsequently, follicular morphology, cellular proliferation (expression of Ki-67, MCM-7) and apoptosis (expression of caspase-3) were evaluated, and data obtained were analysed using generalised linear mixed model and chi square tests. Proportions of intact follicles were higher in Fr (P = 0.0001) and VIT_RT2 (P = 0.0383) in comparison to the other protocols both post warming and after the six-day culture. Generally, most follicles remained at primordial state which was confirmed by the low expression of Ki-67, MCM-7 markers. In conclusion, VIT_RT2 protocol, which has lower equilibration time at room temperature has proven superior thus recommended for vitrification of feline ovarian tissue.

Ki67 Tumor Expression Predicts Treatment Benefit Achieved by Macroscopic Radical Lung-Preserving Surgery in Pleural Mesothelioma-A Retrospective Multicenter Analysis.

Pleural mesothelioma (PM), linked to asbestos-induced inflammation, carries a poor prognosis. Therapy ranges from therapy limitation to aggressive multimodality treatment. Given the uncertainty about treatment benefits for patients, this study aimed to assess the role of Ki67 as a prognostic and predictive parameter in PM. Ki67 was measured in the specimens of 70 PM patients (17 female, 53 male) from two centers and correlated to overall survival (OS) and therapy outcome. The median OS was 16.1 months. The level of Ki67 expression was divided into low (≤15%) and high (>15%). A low value of Ki67 expression was associated with a longer OS (Ki67 ≤ 15%: 31.2 (95% CI 6.5-55.8) months vs. Ki67 > 15%: 11.1 (95% CI 7.7-14.6) months, p = 0.012). The 5-year survival represents 22% in the low Ki67 expression group, in contrast to 5% in the high Ki67 expression group. We found a significant interaction term of Ki67 with multimodality treatment (p = 0.031) translating to an OS of 48.1 months in the low expression Ki67 group compared to 24.3 months in the high Ki67 expression group when receiving surgery within multimodality therapy. Therefore, Ki67 stands out as a validated prognostic and, most importantly, novel predictive biomarker for treatment benefits, particularly regarding surgery within multimodality therapy.

Abstract PO4-03-05: Prognostic value of Ki67 expression in post-treatment tumors of patients with residual triple-negative breast cancer after neoadjuvant chemotherapy

Abstract Introduction Patients with triple-negative breast cancer (TNBC) who do not achieve pathological complete response (pCR) against neoadjuvant chemotherapy (NAC) have a poor prognosis. The prognosis of these patients can be differentiated using various parameters, including the Residual Cancer Burden (RCB) index and tumor-infiltrating lymphocytes. In this study, we took a different angle and aimed to evaluate the prognostic value of post-treatment Ki67 expression, which was examined in tumors following NAC in patients with non-pCR TNBC. Methods A retrospective review of clinical records from February 2008 to December 2021 was conducted of patients from Gangnam Severance Hospital and Asan Medical Center, both in Seoul, South Korea. We included patients with non-metastatic TNBC who underwent NAC including anthracycline and taxane regimens, followed by curative surgery, regardless of adjuvant capecitabine receipt. Ki67 expression and the RCB index were evaluated using residual tumors obtained from surgery. High Ki67 expression was defined as ≥20%. The 5-year recurrence-free survival (RFS) was estimated using Kaplan-Meier analysis, and hazard ratios (HR) were calculated using Cox regression analysis. Results This study included 338 patients with available Ki67 expression data in residual tumors. Among them, 110 patients (30.9%) had low Ki67 expression, while 228 patients (64%) had high Ki67 expression. At a median follow-up of 34 months, those with low Ki67 expression had a 5-year RFS rate of 82.6%, while those with high Ki67 expression had a rate of 58.3%, with a HR of 0.345 (95% CI 0.210-0.565, p&amp;lt; 0.001). When stratified by the RCB index, the 5-year RFS of RCB-I patients was 93%, RCB-II patients 70.2%, and RCB-III patients 40.5%. When assessing survival outcomes based on both Ki67 expression and the RCB index, patients with RCB-I and low Ki67 (n=26) had a 100% 5-year RFS rate. Patients with RCB-I and high Ki67 (n=24) had a rate of 83.3%. Notably, in patients with RCB-III and high Ki67 (n=62), the 5-year RFS rate was 35.5% and there was no significant difference in RFS based on the receipt of adjuvant capecitabine (median RFS: capecitabine - 18 months, observation - 15 months, p-value=0.994). Conclusions Our findings demonstrate the prognostic value of Ki67 expression in residual TNBC after NAC, indicating that cases with low Ki67 expression have a favorable outcome. Combining Ki67 expression with the RCB index allows identification of patients with good residual disease (i.e. low Ki67 expression and RCB-I) who could be potential candidates for de-escalating adjuvant treatments such as capecitabine or pembrolizumab. However, for patients with high Ki67 expression and RCB-III, novel strategies are required to improve survival outcomes beyond the use of capecitabine. Citation Format: Yoonwon Kook, Soo-Young Lee, Seung Ho Baek, Min Ji Kim, Junghyun Kim, Sohyun Moon, Seung Eun Lee, Soong June Bae, Joon Jeong, Sae Byul Lee, Sung Gwe Ahn. Prognostic value of Ki67 expression in post-treatment tumors of patients with residual triple-negative breast cancer after neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-03-05.

Prevalence and risk factors of thyroid nodules in breast cancer women with different clinicopathological characteristics: a cross-sectional study.

Association between breast cancer (BC) and thyroid nodules (TNs) is still unclear. This research was to estimate the prevalence and risk factors of TN in Chinese BC women at initial diagnosis. 1731 Chinese early-stage BC women at initial diagnosis underwent thyroid ultrasound and 1:1 age-matched Chinese healthy women underwent health examination in corresponding period were enrolled for analysis. Prevalence of TN and TI-RADS ≥ 4 TN in BC patients (56.27% and 9.76%) were higher than healthy people (46.04% and 5.49%), respectively, P < 0.001. Among BC patients, prevalence of TN and TI-RADS ≥ 4 TN in hormone receptor (HR)-positive patients (59.57% and 11.81%) were higher than HR-negative patients (48.77% and 5.10%), respectively, P < 0.001, while without difference between HR-negative patients and healthy people. After adjusting for age and BMI, HR-positive patients had higher risk of TN (OR = 1.546, 95%CI 1.251-1.910, P < 0.001) and TI-RADS ≥ 4 TN (OR = 3.024, 95%CI 1.943-4.708, P < 0.001) than HR-negative patients. Furthermore, the risk of TI-RADS ≥ 4 TN was higher in patients with estrogen receptor (ER) positive (OR = 2.933, 95%CI 1.902-4.524), progesterone receptor (PR) positive (OR = 1.973, 95%CI 1.378-2.826), Ki-67 < 20% (OR = 1.797, 95%CI 1.280-2.522), and tumor size < 2cm (OR = 1.804, 95%CI 1.276-2.552), respectively, P < 0.001. Prevalence of TN, especially TI-RADS ≥ 4 TN, in Chinese early-stage BC women was higher than healthy people. HR-positive patients had higher prevalence and risk of TN, while without difference between HR-negative patients and healthy people. The increased risk of TN was correlated with ER-positive, PR-positive, lower Ki-67 expression, and smaller tumor size.

Targeting Unique Features of Quiescent Cancer Stem Cells to Overcome Resistance and Recurrence in Cancer Therapy: A Review

Quiescent cancer stem cells (QCSC) are non-proliferating cells that survive in the G0 phase and have low ki-67 expression and high p27 expression. QCSCs have the ability to evade most chemotherapy, and some subsequent treatments may result in a higher proportion of quiescent cancer stem cells in the tumor. QCSCs are also associated with cancer recurrence rates because they can re-enter the cell cycle to proliferate when tumor environmental conditions are favorable. QCSCs cause high rates of drug resistance and tumor recurrence, therefore it is necessary to understand the properties of QCSCs. QCSCs have a mechanism that regulates the transition between the proliferative phase and the stationary phase in cancer cells, therefore it is necessary to find new treatments to eliminate QCSCs in tumors. In this review, the authors discuss the mechanisms of QCSCs in inducing drug resistance and tumor recurrence as well as therapies to target QCSCs so that the rate of drug resistance and tumor recurrence can be reduced, including in this review: (i) identifying reactive quiescent cancer cells and eliminating them through anticancer reagents. cell cycle dependent; (ii) modulating the transition from the quiescent to the proliferative phase; and (iii) eliminate QCSC by targeting its unique features. Targeting cancer cells that are in proliferating and stationary phase may ultimately be used as a more effective therapeutic strategy for cancer treatment.