High Ki-67 Expression Research Articles

CT feature of irregular extensive ulceration as a predictor of liver metastasis in gastric gastrointestinal stromal tumours.

This study aimed to investigate whether the computed tomography (CT) finding of irregular extensive ulceration (IEU) can serve as a predictor of liver metastasis (LIM) in patients with gastric gastrointestinal stromal tumours (GISTs). This study retrospectively collected clinical and imaging data from 286 patients diagnosed with low-, intermediate-, or high-risk gastric GISTs, or primary lesions with LIM from three medical institutions. The patients were categorised into non-LIM and LIM groups according to whether they had synchronous or metachronous LIM. Multivariate logistic regression analyses were performed to identify significant predictors of LIM. Additionally, receiver operating characteristic (ROC) curve, subgroup, and pathologic-radiologic correlation analyses were conducted. A total of 124 patients were ultimately enroled. There were significant differences in sex, site, growth pattern, size, shape, ulceration and Ki-67 expression between LIM and non-LIM groups. ROC curve analysis demonstrated that IEU had the highest area under the curve for predicting LIM (AUC = 0.842; 95% CI: 0.760-0.924; p < 0.001). Multivariate analysis indicated that IEU was the most significant independent predictor of high LIM risk (OR = 88.62; 95% CI: 2.80-2803.54; p = 0.011). Subgroup analysis showed that IEU was more frequently associated with male sex, age ≤ 55 years, proximal sites, irregular shapes, mixed growth patterns, and a high Ki-67 expression. The CT feature of IEU serves as an independent predictor of LIM in gastric GISTs and is strongly associated with high Ki-67 expression. Question Accurate assessment of LIM risk in patients with gastric GISTs is crucial, yet current non-invasive predictors remain inadequate. Findings IEU on CT is an independent predictor of LIM, with high diagnostic accuracy and a significant association with elevated Ki-67 expression. Clinical relevance IEU on CT scans enables non-invasive risk stratification for LIM in gastric GISTs. Our study refined the assessment of ulceration types, highlighting significant heterogeneity, which may guide personalised treatment strategies.

Clinicopathologic and Genomic Features of Invasive Stratified Mucin-producing Carcinoma of the Uterine Cervix Coexisting With High-grade Squamous Intraepithelial Lesion.

Invasive stratified mucin-producing carcinoma (ISMC) is a specific type of adenocarcinoma of the cervix, which is associated with human papillomavirus infection and often coexists with other types of carcinomas. However, given its rarity, understanding of this disease remains insufficient. We present a unique case of ISMC of the cervix coexisting with a high-grade squamous intraepithelial lesion (HSIL). In addition to histologic and immunohistochemical feature observation, genomic profiling of the 2 lesions was performed. Histologically, the ISMC and HSIL lesions were independent of each other. Aside from the typical morphology, various architectural features of ISMC were observed. Immunohistochemically, the ISMC and HSIL lesions were strongly and diffusely positive for p16 and exhibited high Ki-67 expression. The ISMC lesion was also positive for CK7, MUC5AC, and MUC6, while it was negative for PAX-8. The HSIL lesion was positive for CK5/6 and p40. The combined positive score of PD-L1 was 55. The other markers were all negative in both lesions, and the p53 was wild-type. Next-generation sequencing analysis revealed multiple gene mutations in the ISMC and HSIL lesions. A total of 88 gene mutations were identified in the ISMC lesion, while 20 gene mutations were identified in the HSIL lesion. Three mutations (ERBB2, histidine decarboxylase gene [HDC], and BSN) were detected in the ISMC and HSIL lesions. Both lesions had a low tumor mutation burden and microsatellite-stable status. No copy number-associated variants or structural variations were identified in either lesion. These results suggest that patients with ISMC may benefit from PD-L1 immunotherapy and targeted therapy.

A retrospective study on the prognosis of endoscopic surgery for 385 early glottic cancer patients

Objective: To investigate the prognosis and influencing factors of endoscopic surgery for early glottic carcinoma. Methods: In this retrospective study, we applied the Cox proportional hazards regression model and the random survival forest model to analyze the clinical characteristics of 385 patients [362 males, 23 females, age ranging from 33 to 91 years (62.0±9.6)] who visited the Sixth Medical Center of the General Hospital of the People's Liberation Army from January 2009, to December 2022 and diagnosed with early glottic carcinoma, encompassing variables such as age, gender, T stage, surgical approach, pathological typing, etc. The primary evaluation indicators were overall survival(OS) and disease-free survival rates (DFS). The follow-up duration ranged from 30 to 5,557 days (with a median follow-up time of 1,596 days). Results: After a three-year follow-up, the OS rate for the 385 patients was 95.83%, while the DSF rate was 82.98%. The Cox proportional hazards regression analysis revealed age (HR=2.35, 95%CI: 1.75 to 3.15, P<0.001) and T staging (HR=1.59, 95%CI: 1.13 to 2.23, P=0.019) as predominant factors affecting the OS and DFS. The random survival forest model identified poor tumor differentiation, and high expression of P53 and Ki-67 as predictors of inferior prognosis. Conclusion: Endoscopic surgery for early glottic carcinoma yields favorable short-term OS and reduces short-term recurrence rates, with T-stage emerging as a pivotal factor influencing recurrence. Tumors with poor differentiation and elevated expression of P53 may be indicative of an increased risk of recurrence.

Roles of miR-20a-5p in breast cancer based on the clinical and multi-omic (CAMO) cohort and in vitro studies

MicroRNAs are involved in breast cancer development and progression, holding potential as biomarkers and therapeutic targets or tools. The roles of miR-20a-5p, a member of the oncogenic miR-17-92 cluster, remain poorly understood in the context of breast cancer. In this study, we elucidate the role of miR-20a-5p in breast cancer by examining its associations with breast cancer risk factors and clinicopathological features, and its functional roles in vitro. Tissue microarrays from 313 CAMO cohort breast cancer surgical specimens were constructed, in situ hybridization was performed and miR-20a-5p expression was semiquantitatively scored in tumor stromal fibroblasts, and in the cytoplasm and nuclei of cancer cells. In vitro analysis of the effect of miR-20a-5p transfection on proliferation, migration and invasion was performed in three breast cancer cell lines. High stromal miR-20a-5p was associated with higher Ki67 expression, and higher odds of relapse, compared to low expression. Compared to postmenopausal women, women who were premenopausal at diagnosis had higher odds of high stromal and cytoplasmic miR-20a-5p expression. Cytoplasmic miR-20a-5p was significantly associated with tumor grade. In tumors with high cytoplasmic miR-20a-5p expression compared to low expression, there was a tendency towards having a basal-like subtype and high Ki67. In contrast, high nuclear miR-20a-5p in cancer cells was associated with smaller tumor size and lower odds of lymph node metastasis, compared to low nuclear expression. Transfection with miR-20a-5p in breast cancer cell lines led to increased migration and invasion in vitro. While the majority of our results point towards an oncogenic role, some of our findings indicate that the associations of miR-20a-5p with breast cancer related risk factors and outcomes may vary based on tissue- and subcellular location. Larger studies are needed to validate our findings and further investigate the clinical utility of miR-20a-5p.

Evaluation of Ki-67 expression and large cell content as prognostic markers in MZL: a multicenter cohort study

Marginal zone lymphoma (MZL) can have varied presentations and pathologic features, including high Ki-67 expression ( > 20%) as well as increased numbers of large B cells (LC). However, there are limited data available demonstrating the prognostic significance of these variables in patients with MZL. In this multi-institutional retrospective cohort study of patients with MZL treated at 10 centers, we evaluated the association between the presence of Ki-67 expression and increased LCs on survival and risk of histologic transformation (HT). A total of 785 patients were included (60% with extranodal MZL, 20% with nodal MZL, and 20% with splenic MZL). Among the 440 patients with Ki-67 staining, 22% had high Ki-67 (Ki-67 >20%). The median progression-free survival (PFS) for patients with high Ki-67 was 5.4 years compared to 7.0 years for patients with low Ki-67 (HR = 1.45, 95%CI = 1.03–2.05). Ki-67 > 20% strongly correlated with high LDH level. The risk of HT was higher in patients with increased Ki-67 than those without (5-year risk, 9.8% vs 3.87%, p = 0.01). Twelve percent of patients had LC reported on biopsy with 6% having >10% LC. The presence of LC was associated with high Ki-67 (p < 0.001), but not associated with shorter PFS or overall survival (OS). The cumulative risk for HT was higher in patients with LC compared to those without LC (5-year risk, 9.4% vs 2.9%, p = 0.04). Receipt of anthracycline-based therapy did not impact PFS or OS in either group. Ki-67 staining >20% was a prognostic factor for worse survival and strongly correlated with elevated LDH. Novel therapies should be investigated for their potential ability to overcome the high-risk features in MZL. Our data reinforce the importance of obtaining biopsies at relapse or progression, particularly in patients with baseline high Ki-67 and increased LCs, given their increased risk for HT.

Performance of radiomics in preoperative determination of malignant potential and Ki-67 expression levels in gastrointestinal stromal tumors: a systematic review and meta-analysis.

Empirical evidence for radiomics predicting the malignant potential and Ki-67 expression in gastrointestinal stromal tumors (GISTs) is lacking. The aim of this review article was to explore the preoperative discriminative performance of radiomics in assessing the malignant potential, mitotic index, and Ki-67 expression levels of GISTs. We systematically searched PubMed, EMBASE, Web of Science, and the Cochrane Library. The search was conducted up to 30 September 2023. Quality assessment was performed using the Radiomics Quality Score (RQS). A total of 35 original studies were included in the analysis. Among them, 26 studies focused on determining malignant potential, three studies on mitotic index discrimination, and six studies on Ki-67 discrimination. In the validation set, the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of radiomics in the determination of high malignant potential were 0.74 (95% CI=0.69-0.78), 0.90 (95% CI=0.83-0.94), and 0.81 (95% CI=0.14-0.99), respectively. For moderately to highly malignant potential, the sensitivity, specificity, and AUC were 0.86 (95% CI=0.83-0.88), 0.73 (95% CI=0.67-0.78), and 0.88 (95% CI=0.27-0.99), respectively. Regarding the determination of high mitotic index, the sensitivity, specificity, and AUC of radiomics were 0.86 (95% CI=0.83-0.88), 0.73 (95% CI=0.67-0.78), and 0.88 (95% CI=0.27-0.99), respectively. When determining high Ki-67 expression, the combined sensitivity, specificity, and AUC were 0.74 (95% CI=0.65-0.81), 0.81 (95% CI=0.74-0.86), and 0.84 (95% CI=0.61-0.95), respectively. Radiomics demonstrates promising discriminative performance in the preoperative assessment of malignant potential, mitotic index, and Ki-67 expression levels in GISTs.

High Ki-67 Expression Predicting a Risk Factor for the Progression of Disease within 24 Months and Microenvironment in Follicular Lymphoma

Most follicular lymphomas (FLs) demonstrate an indolent clinical course with favorable outcomes; however, a fraction of patients experiences progression of disease within 24 months (POD24) and has adverse outcomes. This study aimed to determine the predictive risk factors for POD24 in patients with FL, and the characteristics of the microenvironment in FL with POD24. By multivariate analysis, we revealed that increased Ki-67 expression was associated with POD24 events in patients with FL (hazard ratio [HR]: 6.29, 95% confidence interval [CI]: 1.96–20.22, p = 0.0020). Additionally, patients with FL with POD24 demonstrated immune cell reduction by immunohistochemistry analysis. Our results help better understand the therapeutic strategies for FL with POD24.

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.

Expression of histone methyltransferase WHSC1 in invasive breast cancer and its correlation with clinical and pathological data

BackgroundThe WHSC1 protein facilitates specific dimethylation of histone H3 at the K36 position, enhancing gene transcription and expression. Studies have confirmed its high expression in diverse malignant tumors. We aimed to identify novel molecular markers to assess the biological behavior of breast cancer cells. MethodsWe conducted a comprehensive analysis of mRNA expression in breast cancer and adjacent tissues based on TCGA data. We enrolled 141 breast cancer patients treated at the First Affiliated Hospital of Fujian Medical University between 2012 and 2016. Patient clinical information and pathological specimens were obtained. We utilized tissue microarray (TMA) technology. We employed the chi-square test for between-group comparisons, with p < 0.05 indicating statistical significance. Furthermore, we analyzed the associations between WHSC1 expression and clinical or pathological data. ResultsWHSC1 mRNA expression was significantly higher in breast cancer tissues than in adjacent tissues (p < 0.001). Moreover, high WHSC1 protein expression in breast cancer was associated with several important clinical parameters, such as pathological type (p = 0.007), high Ki67 expression(Ki67＞20 %) (p < 0.001), lymph node metastasis (p < 0.001), T stage (p = 0.011), N stage (p < 0.001), postoperative pathological stage (p < 0.001), premenopausal status (p = 0.004), and positive HER2 status (p < 0.001). Multivariate regression analysis showed that high WHSC1 expression, elevated Ki67 levels, and positive HER2 status were independent risk factors for axillary lymph node metastasis in breast cancer patients. ConclusionWHSC1 protein expression is upregulated in breast cancer patients and represents an independent risk factor influencing axillary lymph node metastasis, highlighting its potential significance as a strong candidate biomarker.

Expression of Ki-67 in Invasive Breast Carcinoma and Its Correlation With Different Clinicopathological Features.

Introduction Worldwide, breast cancer is still the most common cancer that affects women. Breastcancer prognosis is based on a number of clinical and pathological indicators. Further features are needed to predict early metastasis andprognosis of patients with breast carcinoma, as the current pathological characteristics, such as tumor differentiation, vascular infiltration, and TNM (tumor, node, and metastasis) staging, cannot fully describe the early metastatic biological behavior in breast carcinoma. High Ki-67 expression is seen to be associated with worse survival in cancer patients. Hence, this study was conducted to study the utility of Ki-67as a prognostic marker in invasive breast carcinoma and its association with known clinicopathological factors. Methodology The study was a hospital-based cross-sectional study carried out in the Histopathology Section of the Department of Pathology, Shri BM Patil Medical CollegeHospital and Research Centre, Bijapur Lingayat District Education (BLDE) (Deemed to be University), Vijayapura. The study was conducted between September 1, 2022, and April 30, 2024. The study population consisted of 55 cases of mastectomy specimens of primary breast cancer admitted to our hospital. Data regarding the patient's age, tumor size, histological type, histological grade, lymph node status, and vascular invasion were noted from medical records. Immunohistochemical staining for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2/neu (HER2/neu) proto-oncogene, and Ki-67 markers was performed according to standard protocol. The relationship of Ki-67with these clinicopathological parameters was analyzed statistically. Results In the current study, high-grade Ki-67 nuclear positivity was seen in 30 cases out of 55 cases, and low-grade Ki-67 was seen in the remaining 25 cases. The association of Ki-67 with tumor size and histological grade showed statistical significancewith a p-value of less than 0.05 and 0.001, respectively. However, no statistical significance was seen with lymph node status, vascular invasion, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2/neu (HER2/neu)proto-oncogene status with p-values greater than 0.05. Conclusion The expression of Ki-67 was statistically significant with histological grading and tumor size in our study. Immunohistochemical determination of the Ki-67 proliferation index should be performed in routine cases of breast cancerto obtain clinically useful information on tumor aggressiveness as reflected in their proliferative rate. Hence, Ki-67 can be used as a predictive and prognostic marker in managing breast cancer patients.

Dynamic Peripheral T-Cell Analysis Identifies On-Treatment Prognostic Biomarkers of Atezolizumab plus Bevacizumab in Hepatocellular Carcinoma

Introduction: Variability in response to atezolizumab plus bevacizumab (AB) treatment of hepatocellular carcinoma (HCC) underscores the critical need for the development of effective biomarkers. We sought to identify peripheral blood biomarkers reflecting response to AB treatment. Methods: We analyzed dynamic changes in peripheral blood mononuclear cells from a prospective, multicenter cohort of 65 patients with HCC, using flow cytometry to evaluate the T-cell population before and 3 weeks after the first AB treatment. Results: We found a unique response of the CD8+ T cells in terms of both frequency and phenotype, in contrast to CD4+ T cells and regulatory T cells. Notably, CD8+ T cells showed significant changes in expression of Ki-67 and T-cell immunoreceptors with Ig and ITIM domains (TIGIT). These distinct responses were observed particularly in the programmed cell death receptor-1 (PD-1)+ subpopulation of CD8+ T cells. Interestingly, the baseline differentiation status of PD-1+CD8+ T cells, particularly the central memory T-cell subset, correlated positively with greater proliferation (higher Ki-67 expression) of PD-1+CD8+ T cells after treatment. Moreover, effector memory cells expressing CD45RA correlated negatively with the increase in TIGIT+/PD-1+CD8+ T cells. The increase in TIGIT+/CD8+ T cells was associated with the development of immune-related adverse events, whereas increase in Ki-67+/PD-1+CD8+ T cells was associated with the better objective response rate. Importantly, dynamic shifts of Ki-67+/PD-1+CD8+ T cells and TIGIT+/CD8+ T cells significantly predicted progression-free survival and overall survival, as confirmed by multivariate analysis. Conclusion: These findings highlight the potential of dynamic changes in CD8+ T cells as an on-treatment prognostic biomarker. Our study underscores the value of peripheral blood profiling as a noninvasive and practical method for predicting the clinical outcomes of AB treatment in patients with HCC.

738. WHICH PATIENTS WITH BARRETT'S ESOPHAGUS ARE MOST LIKELY FOR MALIGNIZATION? UNI AND MULTIVARIANT STUDY. RISK GROUPS

Abstract Background Barrett's esophagus (BE) is a premalignant pathology that can sometimes progress to adenocarcinoma (ADC) of the esophagus. Although the percentage of malignancy is low, one in every 200 patients/year, in the world literature there is great variability (0,1-1 % patients/year). This important discrepancy arises because we know that not all patients with BE have the same risk of malignancy. The objective of this work is allowing us to stratify patients according to their risk of malignancy. Methods We have 147 patients with a mean (range) follow-up is 13.3 years (2-33). During this period, 16 patients progressed to early esophageal ADC (10.8%), malignancy rate of 0.8 patients/year. Two study groups were obtained: 1. Patients with non-malignant BE: 131 (median age 43 years (10-79). 96 men (73%). 2. Patients with malignant BE: 16 (median age 51 years (21-74). 15 men (94%). Statistical method A univariate and multivariate statistical study was carried out to detect which factors have a greater risk of malignancy. We analyzed epidemiological, clinical, endoscopic, histological, functional factors (motility and pH) and therapeutic. RESULTS Age: 22 patients over 65 years, 22.7% of malignancy, and only 8.8% patients under 65 (p=0.05, OR=3.048). Sex 13.5 % men progressed and only 2.8 % women (p=0.045). Familial Barrett's esophagus was positive in 6 patients, 66.6% malignant, while only 8.5% without familial BE progressed (p=0.0001). EB length: patients with metaplastic segments greater than 4 cm have a 12 times greater risk of malignancy. Low grade dysplasia: 39 % patients had a diagnosis of LGD became malignant, and only 7 % patients with not LGD (p&amp;lt;0.0001, OR 8.49). Proliferation Ki67 and p53 high expression patients were malignant in 69.2% and 91.7 % (p&amp;lt;0.0001, OR 29.25 and 242.00). Esophageal functional studies 22.6% patients with esophageal body hypomotility became malignant and only 3.2 % with preserved esophageal body motility (p=0.001, OR 8.75). Neither the mean LES pressure nor the percentage of patients with hypotensive LES were statistically significant. 20.4% patients with severe acid reflux (pH &amp;lt;4 greater than 24%) became malignant versus 6.1 % patients suffered from less reflux (p=0.009, OR 3.93). Type and effectiveness of treatment Malignancy according to treatment, no differences are observed (10 % and 11.6 % en medical and surgical groups). Only 3.9 % patients with effective treatment became malignant, while in 48.1% who failed treatment (p=0.0001, OR 22.9). Multivariate analysis Only LGD reached statistical significance (p=0.007) with an OR 7.18, and the high expression of p53 (p&amp;lt;0.0001) with an OR 89.14. Risk groups Based on statistical analysis, we have established three risk groups (figure 1). We included 5 patients with High Risk (3.5%, F-U 8.6 years), all malignant (100%, 11.6% patients/year). Intermediate Risk 33 patients (22.5%, F-U 11.97 years, with progression in 11 patients (33.3%, 2.7% patients/year). Low Risk to 109 patients (74%), none became malignant. (p&amp;lt;0.0001, OR: 1.78). Conclusion In patients with high and intermediate risk, therapeutic options and endoscopic follow-up should be different than in patients with the absence of these disease characteristics, classified as low risk.

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.

Prognostic and Clinical Significance of the Proliferation Marker MCM7 in Breast Cancer.

Minichromosome maintenance complex component 7 (MCM7) plays an essential role in proliferation and DNA replication of cancer cells. However, the expression and prognostic significance of MCM7 in breast cancer (BC) remain to be defined. In this study, we aimed to evaluate the role of MCM7 in BC. We conducted immunohistochemistry staining of MCM7 in 1,156 operable early-stage BC samples and assessed MCM7 at the transcriptomic levels using publicly available cohorts (n = 13,430). MCM7 expression was evaluated and correlated with clinicopathological parameters including Ki67 labelling index and patient outcome. At the transcriptomic level, there was a significant association between high MCM7 mRNA levels and shorter patient survival in the whole cohort and in luminal BC class but not in the basal-like molecular subtype. High MCM7 protein expression was detected in 43% of patients and was significantly associated with parameters characteristic of aggressive tumour behaviour. MCM7 was independently associated with shorter survival, particularly in oestrogen receptor-positive (luminal) BC. MCM7 stratified luminal tumours with aggressive clinicopathological features into distinct prognostic groups. In endocrine therapy-treated BC patients, high MCM7 was associated with poor outcome, but such association disappeared with administration of adjuvant chemotherapy. Patients with high expression of Ki67 and MCM7 showed worst survival, while patients with double low expression BC showed the best outcome compared with single expression groups. The current findings indicate that MCM7 expression has a prognostic value in BC and can be used to identify luminal BC patients who can benefit from adjuvant chemotherapy.

Homotypic cell-in-cell structure as a novel prognostic predictor in non-small cell lung cancer and frequently localized at the invasive front

Homotypic cell-in-cell structures (hoCICs) are associated with tumor proliferation, invasion, and metastasis and is considered a promising prognostic marker in various cancers. However, the role of hoCICs in non-small cell lung cancer (NSCLC) remains unclear. Tumor tissue sections were obtained from 411 NSCLC patients. We analyzed the relationship between clinicopathological variables and the number of hoCICs. LASSO and multivariate Cox regression analysis were employed to identify prognostic factors for NSCLC. The impact of hoCICs on overall survival (OS) and disease-free survival (DFS) was assessed using the Kaplan–Meier curves and log-rank test. Prognostic models for OS and DFS were developed and validated using the C-index, time-dependent area under the curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), calibration curves and decision curve analysis (DCA). Among the cohort, 56% of patients had hoCICs while 44% did not. Notably, hoCICs were primarily found at the tumor invasion front. Male gender, smoking, squamous cell carcinoma, low differentiation, tumor size ≥ 3 cm, advanced TNM stage, lymph node metastasis, pleural invasion, vascular invasion, necrosis, P53 mutation, and high expression of Ki-67 were identified as relative risk factors for hoCICs. Furthermore, hoCICs was found to be a significant prognostic factor for both OS and DFS, with higher frequencies of hoCICs correlating with poorer outcomes. We constructed nomograms for predicting 1-, 3-, and 5-year OS and DFS based on hoCICs, and the calibration curves showed good agreement between the predicted and actual outcomes. The results of the C-index, time-dependent AUC, NRI, IDI, and DCA analyses demonstrated that incorporating hoCICs into the prognostic model significantly enhanced its predictive power and clinical applicability. HoCICs indicated independent perdictive value for OS and DFS in patients with NSCLC. Furthermore, the frequent localization of hoCICs at the tumor invasion front suggested a strong association between hoCICs and tumor invasion as well as metastasis.

Radiomics nomogram based on CT radiomics features and clinical factors for prediction of Ki-67 expression and prognosis in clear cell renal cell carcinoma: a two-center study

ObjectivesTo develop and validate a radiomics nomogram combining radiomics features and clinical factors for preoperative evaluation of Ki-67 expression status and prognostic prediction in clear cell renal cell carcinoma (ccRCC).MethodsTwo medical centers of 185 ccRCC patients were included, and each of them formed a training group (n = 130) and a validation group (n = 55). The independent predictor of Ki-67 expression status was identified by univariate and multivariate regression, and radiomics features were extracted from the preoperative CT images. The maximum relevance minimum redundancy (mRMR) and the least absolute shrinkage and selection operator algorithm (LASSO) were used to identify the radiomics features that were most relevant for high Ki-67 expression. Subsequently, clinical model, radiomics signature (RS), and radiomics nomogram were established. The performance for prediction of Ki-67 expression status was validated using area under curve (AUC), calibration curve, Delong test, decision curve analysis (DCA). Prognostic prediction was assessed by survival curve and concordance index (C-index).ResultsTumour size was the only independent predictor of Ki-67 expression status. Five radiomics features were finally identified to construct the RS (AUC: training group, 0.821; validation group, 0.799). The radiomics nomogram achieved a higher AUC (training group, 0.841; validation group, 0.814) and clinical net benefit. Besides, the radiomics nomogram provided a highest C-index (training group, 0.841; validation group, 0.820) in predicting prognosis for ccRCC patients.ConclusionsThe radiomics nomogram can accurately predict the Ki-67 expression status and exhibit a great capacity for prognostic prediction in patients with ccRCC and may provide value for tailoring personalized treatment strategies and facilitating comprehensive clinical monitoring for ccRCC patients.

High Expression of Vascular Endothelial Growth Factor, Ki-67, and Protein 53 are Risk Factors for Poor Response of Paclitaxel-Carboplatin Neoadjuvant Chemotherapy in Stadium IB3, IIA2, and IIB Cervical Cancer.

The therapeutic strategy for stage IB3, IIA2, and IIB cervical cancer is still controversial. The modalities are chemoradiation, radical hysterectomy surgery, or administration of neoadjuvant chemotherapy followed by radical hysterectomy. Response to chemotherapy is determined by tumor vascularization or angiogenesis, proliferative activity, and genetic instability of cervical cancer. The marker of tumor cell proliferation is the Ki-67 protein. In cervical cancer, the p53 gene is suppressed by human papillomavirus (HPV). The HPV E6 protein promotes the degradation of p53 thereby inhibiting stabilization and activation of p53. This study aimed to prove that high expression of VEGF, Ki-67, and p53 are risk factors for a poor response to neoadjuvant chemotherapy. This was a case-control study that was conducted at the Department of Obstetrics and Gynecology in one tertiary hospital in Denpasar from October 2021 to April 2022. There were 56 samples included in this study, which were divided into two equal groups, namely good response and poor response to neoadjuvant chemotherapy. Data were analyzed using the software SPSS-24 including the Kolmogorov-Smirnov normality test, Chi-square, and multiple regression logistics. Data were presented in tables and described narratively. It was found that the risk of a poor response to chemotherapy on the expression of VEGF VEGF, Ki-67, and p53 were 11.5, 15.0, and 8.33 times, respectively. We obtained a formula for calculating chemotherapy response, y = -7.3+ 1.6 VEGF + 1.6 Ki-67 + 1.8 p53. High VEGF, Ki-67, and p53 expressions were scored 1, and low expressions were scored 2. The limit value used is 0.05. The result y < 0.05 means the risk of poor response to chemotherapy and the value of y > 0.05 means good response. This formulation can be used as a parameter to assess the risk of poor response to neoadjuvant chemotherapy in stage IB3, IIA2, and IIB cervical cancer which can be applied in clinical practice in the treatment of cervical cancer.

The Prognostic Role of Fibulin-2 and Ki-67 Index in Patients with Meningioma: A Study among Minangkabau Ethnicity.

To analyze the association between fibulin-2 and Ki-67 index with histopathological grade and other clinicopathological factors in patients with meningioma among the Minangkabau ethnic group. This cross-sectional observational study uses 50 specimens comprising 25 low-risk meningioma cases and 25 high-risk meningioma cases obtained at three anatomical pathology laboratories in Padang, West Sumatra, Indonesia, between 2019 and 2022. All samples were stained using an immunohistochemistry procedure with Ki-67 and fibulin-2. The chi-square test was used to assess IBM SPSS statistics version 26 for Windows was used to assess the association of Ki-67 and fibulin-2 with the histopathological grade. The p-value of <0.05 was considered significant. We found a significant association between Ki-67 (p = 0.013) or fibulin-2 (p = 0.001) expression with histopathological grade of meningioma. High histopathological grade has high expression of Ki-67 and fibulin-2, with Odds ratio (OR) of 13.500 (1.556-117.137) and 10.028 (2,738-36,722), respectively. Fibulin-2 expression was also associated with the age of patients (p = 0.020). The low age group (<50) has high expression of fibulin-2 (OR 0.196 (0.056-0.691). Conclusion: Ki-67 and fibulin-2 were associated with the histopathological grade of meningioma, while fibulin-2 is also associated with age in the Minangkabau ethnic group.

Recurrence in Eyelid Sebaceous Carcinoma: A Multicentric Study of 418 Patients.

Local recurrence predicts dismal prognosis in eyelid sebaceous carcinoma (SC). Recurrence predictors vary across studies. Accurate recurrence estimation is essential for individualized therapy in eyelid SC. This study aims to identify recurrence predictors and develop a nomogram for personalized prediction in eyelid SC. We conducted a multicenter retrospective cohort study. Chart reviews were performed in 418 consecutive patients with eyelid SC. All patients were followed up after their initial surgery. Multivariate Cox regression was used to explore the independent predictors of recurrence. A nomogram for recurrence prediction was developed and validated with bootstrap resampling. The predictive accuracy and discriminative ability were compared with the Tumor, Node, Metastasis (TNM) staging system. Over a median of 60-month follow-up, 167 patients (40%) had local recurrence. The median time from diagnosis to recurrence was 14months. The 1-year cumulative recurrence rate was 18%. Diagnostic delay (hazard ratio [HR] = 1.01, 95% confidence interval [CI] = 1.00-1.01, P = 0.001), orbital involvement (HR = 4.47, 95% CI = 3.04-6.58, P < 0.001), Ki67 (HR = 1.01, 95% CI = 1.00-1.02, P = 0.008) and initial surgery of Mohs micrographic surgery with intraoperative frozen section control (HR = 0.53, 95% CI = 0.35-0.80, P = 0.003) were independent influencing factors of recurrence. A nomogram integrating these four factors combined with pagetoid spread displayed satisfactory discriminative ability (C-index = 0.80-0.83; area under the curve [AUC] = 0.82-0.84), which compared favorably than TNM staging (all P < 0.05). The recurrence rate is high in eyelid SC. Early detection and primary resection with Mohs micrographic surgery are recommended in controlling recurrence. Patients with orbital involvement, high Ki67 expression, and pagetoid spread may require adjuvant measures. This nomogram offers more accurate recurrence estimates, aiding in therapeutic decision making.

A Mature Tertiary Lymphoid Structure with a Ki-67-Positive Proliferating Germinal Center Is Associated with a Good Prognosis and High Intratumoral Immune Cell Infiltration in Advanced Colorectal Cancer.

Tertiary lymphoid structures (TLSs) are complex lymphocyte clusters that arise in non-lymphoid tissues due to inflammation or cancer. A mature TLS with proliferating germinal centers is associated with a favorable prognosis in various cancers. However, the effect of TLS maturity on advanced colorectal cancer (CRC) remains unexplored. We analyzed the significance of TLS maturity and tumor Ki-67 expression in surgically resected tumors from 78 patients with pathological T4 CRC. Mature TLS was defined as the organized infiltration of T and B cells with Ki-67-positive proliferating germinal centers. We analyzed the relationship between TLS maturity and intratumoral immune cell infiltration. Mature TLS with germinal center Ki-67 expression was associated with microsatellite instability and improved survival; however, high tumor Ki-67 expression was associated with poor survival in the same cohort. Multivariate analysis identified the absence of mature TLS as an independent predictor of poor post-recurrence overall survival. Intratumoral infiltration of T lymphocytes and macrophages was significantly elevated in tumors with mature TLS compared to those lacking it. High Ki-67 levels and absent mature TLS were identified as poor prognostic factors in advanced CRC. Mature TLS could serve as a promising marker for patients at high-risk of CRC.