Ki-67 Values Research Articles

Retrospective Evaluation of Cases Undergoing Stereotaxic Brain Biopsy.

Objective: The aim of this study is to evaluate the demographic, radiological and histopathological findings, tumoral biomarkers, and survival rates of patients who underwent a stereotactic brain biopsy and those diagnosed with glioblastoma, metastasis, and lymphoma, and the changes in the diagnosis distribution over the years. Materials and Methods: The patients who underwent stereotactic biopsy in our clinic between 2012 and 2020 were evaluated retrospectively. Metastasis, glioblastoma, and lymphoma cases were evaluated as three main groups and the others were excluded. P53 gene expression, isocitrate dehydrogenase (IDH) mutation, and Ki-67 values in glioblastoma cases and Bcl-2, Bcl-6 proteins, and Ki-67 values in lymphomas and their relationship with survival were evaluated. Results: High p53 expression was observed in 27.5% cases diagnosed with glioblastoma. IDH mutation was negative in all glioblastoma cases. Presence of Bcl-2 and Bcl-6 proteins was not associated with survival in lymphomas. Survival rate was significantly higher in cases diagnosed with lymphoma (26.9%) compared to those diagnosed with glioblastoma. A statistically significant increase was determined in patients diagnosed with lymphoma considering the distribution of diseases and incidence and in the distribution of other diagnoses over the years ( p < 0.05). Conclusion: As per the distribution of the disease in recent times, it has been observed that there is an increase in lymphoma cases. Histopathology and biomarkers have great importance in the diagnosis and treatment of cerebral lesions. We think that our findings will be supported by studies in which larger patient population and detailed biomarkers will be studied.

Comparison of Ki67 Proliferation Index in Gastrointestinal Non-Hodgkin Large B-Cell Lymphomas: The Conventional Method of Evaluation or AI Evaluation?

The most common NHL subtype in SEEU is DLBCL (39%), and it manifests with a variety of cellular morphologies and a high proliferation index. Also, the GI tract is the most common site of extranodal NHLs, and most NHLs involving the GI tract are of B-cell lineage, of which diffuse large B-cell lymphoma is the most common subtype, irrespective of location. The last few years have seen digital pathology as a vital technology that has a positive impact on diagnostics, but studies on the use of DP for lymphoma identification, however, are still restricted to only determining whether a tumor is present or absent. Using the example of cases of malignant NHL, we aim to investigate the diagnostic utility of DP using QuPath software in evaluating the proliferation index and the prognostic significance and to show that improved visualization and analysis contribute to the convergence of these complementary diagnostic modalities for lymphomas. The average proliferation index (Ki67) was 58.33% with values between 10% and 85%. After the stratification of the cases, an increased proliferation index was observed in the majority of cases (53.33%), and this aspect was associated with the advanced age of the patients (p = 0.045). Visual assessment provides lower Ki67 values than automated digital image analysis. However, the agreement coefficient between the conventional method and the AI method indicates an excellent level of reliability (ICC1-0.970, ICC2-0.990). The multivariate analysis revealed that in the cases where the proliferation index Ki67 is high (˃70%), the IPI score represents an important risk factor predicting mortality (HR = 10.597, p = 0.033).

The immune microenvironment characterisation and dynamics in hormone receptor-positive breast cancer before and after neoadjuvant endocrine therapy.

Oestrogen receptor positive (ER+)/HER-2 negative breast cancer (BC) is considered to be an immunologically cold tumour compared to triple negative breast cancer. Therefore, the tumour microenvironment (TME) of ER+/HER-2 negative BC is understudied. The aim of this project is to investigate the TME and the immune response during neoadjuvant endocrine therapy (NET) and to correlate this with the treatment response in a real life setting. Expression of immune checkpoint receptors and immune cells was examined immunohistochemically, pre- and post-NET in a cohort of 56 ER+/HER-2 negative BC patients. They were treated with tamoxifen (n = 16), an aromatase inhibitor (n = 40) or a combination of an aromatase inhibitor with a PI3K inhibitor (n = 11) for a median duration of 6 months (range 1-32 months). Immunohistochemical staining with monoclonal antibodies for PDL-1, PD-1, TIM-3, LAG-3, CTLA-4, CD4, CD68 and FOXP3 were performed. All staining procedures were done according to validated protocols, and scoring was done by a pathologist specialized in breast cancer. Positivity was defined as staining >1% on TILs. Response to NET was evaluated according to tumour size change on imaging and Ki-67 change. The median age was 61.02 (37-90) years. Diameter of tumour size decreased with a mean of 8.1 mm (-16 mm to 45 mm) (p < 0.001) during NET and the value of Ki-67 value decreased with a median of 9 after NET (p < 0.001). An increase in PD-L1 expression after NET showed a trend towards significant (p = 0.088) and CD-4+ T cells significantly increased after NET (p = 0.03). A good response to NET defined as a decrease in tumour size and/or decrease of Ki-67 was found to be associated with a longer duration of NET, a change of CD4+ T-cells and a higher number of CD68+ tumour-associated macrophages before the start of NET. The immune microenvironment plays an important role in ER+/HER-2 negative BC. NET influences the composition and functional state of the infiltrating immune cells. Furthermore, changes in the immune microenvironment are also associated with treatment response.

Identifying the optimal cutoff point of Ki-67 in breast cancer: a single-center experience.

Ki-67 is associated with breast cancer subtypes, but the optimal cutoff point of Ki-67 has not been established in our center. We evaluated the cutoff point of Ki-67 in breast cancer and analyzed the associations among Ki-67, clinicopathological features, and prognosis. The clinicopathological data and prognostic information of patients with breast cancer treated in our center were retrospectively collected, and the optimal cutoff point of Ki-67 was determined by univariate and multivariate survival risk analyses. The cutoff point was used to group the patients, and the differences in the clinicopathological features and prognosis were analyzed between the two groups. In total, 609 patients with estrogen receptor-positive and human epidermal growth factor receptor 2-negative primary breast cancer were enrolled. The mean Ki-67 value was 22.3% ± 15.4%, the median was 20%, and a cutoff point of 30% was an independent factor influencing recurrence-free survival. When 30% was used as the cutoff point, patients with a Ki-67 value of ≤30% had a better prognosis and lower tumor malignancy. The optimal cutoff point of Ki-67 in breast cancer in our center is 30%.

Factors Predicting Response in Breast Cancer Receiving Neoadjuvant Therapy and the Role of Ki67 Labeling Index.

To determine the predictive value of Ki67 on pathological complete response (pCR) of breast and axilla regions in breast cancer (BC) patients receiving neoadjuvant therapy (NAT). Descriptive study. Place and Duration of the Study: Departments of Medical Oncology, Sirnak State Hospital, Aydin State Hospital, Manisa Celal Bayar University, and Dokuz Eylul University, from November 2010 to July 2022. PCR and various histopathological parameters were evaluated for BC patients receiving NAT. The Youden Index method was used to find the cut-off value for the Ki67 variable according to the receiver operating characteristic (ROC) curve. This value was obtained as 77.5. Breast and axillary responses were individually evaluated to assess response to NAT. Univariate and multivariate logistic regression analysis were used to predict both breast and axillary pCR. A total number of 280 females receiving NAT for BC were included in the study. Multivariate analysis for breast pCR to NAT showed that Ki67 index (>77.5 vs <77.5, p=0.047) was statistically significant marker. While Ki67 index was significant for breast pCR in both univariate and multivariate analyses, the same was not observed on axillary response (p=0.387). High Ki67 level was significantly associated with breast pCR in BC patients receiving NAT, but a similar effect was not observed on axillary pCR. These findings suggest that breast and axilla tissues have a biological differences in treatment responses. Axillary response, Breast cancer, Ki67 Labeling Index, Neoadjuvant therapy, pathological complete response.

Are we using the right cut-offs to obtain maximum information from Ki-67 in patients with early breast cancer?

e12567 Background: Ki-67 is one of the most critical prognostic proliferation markers in breast cancer, used on a large scale by oncologists to select treatment options. This study aimed to validate Ki-67 as a prognostic marker and establish the optimal Ki67 cut-offs for stratifying patient prognosis and treatment decisions. Methods: Medical files of 582 consecutive patients with early breast cancer (stage IB-IIIA) who underwent surgery as a first treatment in our institution between 2005-2019 were retrospectively reviewed. Values of Ki-67 were divided into 5 categories: 0-9%, 10-19%, 20-29%, 30-39%, and more than 40%. Results: Kolmogorov-Smirnov and Shapiro-Wilk tests showed that the patient’s age (yrs) at diagnostic, Ki-67 (in %), tumor size (in mm), estrogen and progesterone receptors abundance (%), exhibit normal distributions (p &lt; 0.05). Median age at diagnosis was 54.8 (± 11.5) years and mean Ki-67 of 25.5 ± 16.5 and a median value of 20. Stage distribution was: stage IB 5.5%, IC 12%, IIA 46.6%, IIB 20.4%, IIIA 15.5%. The mean tumor dimension at diagnosis was 21.3 mm. After a median follow-up of 48 months (6-118), estimated disease-free survival rates (DFS) for all patients at 3 and 5 years were 92% and 79%. Disease-free survival rates at 5 years was 96% for patients with Ki-67 0-9%, 90% for patients with Ki-67 10-19%, 80% for patients with Ki-67 20-29%, 75% for patients with Ki-67 30-39%, and 72% for patients with Ki-67 more than 40%. The difference between the median DFS and each ki67 category was statistically significant (p &lt; 0.0001). Using the fit of mixture method, we identify a new cut-off of 29% that negatively predicts DSF for patients (HR = 4.51 95% CI = 1.69-12.04, p = 0.001). Pearson correlation coefficients (p &lt; 0.05) for Ki-67 and DFS, age, ER%, PR%, p53, and tumor size were -0.110, -0.096, -0.139, -0.136, 0.301, and 0.175, respectively. Moreover, DFS was also negatively correlated (p &lt; 0.01) with the patient’s age (-0.106) and tumor size (-0.180). Though the correlation coefficients were small, they oriented the creation of linear models of DFS as a dependent variable and Ki-67, tumor size, and age. DFS has a statistically significant dependence only on the first two variables (standardized coefficients -0.103, p = 0.045 and -0.161, p = 0.02). Conclusions: Ki-67 is a strong prognostic factor in early breast cancer patients. New Ki-67 cut-off levels that may be used in clinical practice were identified. In addition, multivariate analysis showed a significant statistical influence of other factors, such as Ki67 and tumor size. Such correlations can be the basis of a scoring system for progression risk.

Comparison of different cyclin-dependent kinase inhibitors and KI-67 levels on survival and toxicity in breast cancer treatment.

As cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors, which play a crucial role in the cell cycle, palbociclib and ribociclib are two novel drugs that are recently being used in the treatment of breast cancer. Despite targeting the same pathway, these agents have different molecular activities and processes. KI-67 is known to play a significant role in cell proliferation that has been related to prognosis. This study investigated the impact of palbociclib, ribociclib, and KI-67 on toxicity and survival in breast cancer treatment.The study included 140 breast cancer patients in total. Patients were divided into groups based on the use of different CDK inhibitors and KI-67 values. Mortality, progression, treatment response rates, frequency, and severity of adverse events were assessed retrospectively.The patients in our study had an average age of 53.62±12.71 years, and 62.9% of them were diagnosed at an early stage. 34.3% (n=48) of the patients progressed after receiving treatment, while 19.3% (n=27) of the patients died. The median follow-up time was 576 days, the maximum follow-up time was 1,471 days, and the median time to progression was 301 days (min=28-max=713). Mortality, progression, and treatment response rate between two different CDK inhibitors or KI-67 groups revealed no statistically significant differences.Our data show a comparison between the effectiveness of palbociclib and ribociclib, and no noticeable difference is found in breast cancer patients' survival, progression, or severity of adverse effects. Likewise, there is no meaningful difference in KI-67 expression subgroups between progression and survival following treatment.

Identifying determinants of pathologic complete response in patients with breast cancer after receiving neoadjuvant systemic therapy.

e12622 Background: In locally advanced breast cancer, neoadjuvant systemic therapy aims to downstage the disease, clear micrometastasis, assess chemosensitivity, and allow for breast conserving surgery. The attainment of a Pathologic Complete Response (pCR) has been associated with improved event free survival (EFS) and improved overall survival (OS) among various studies. We aim to identify clinicopathological factors which may influence pCR. Methods: This is a single center retrospective study of patients diagnosed with locally advanced breast cancer from 2017-2022 who received neoadjuvant therapy and investigating predictors of pCR in this subset of patients. Descriptive statistics were used to summarize the baseline characteristic variables. Variables relating to pCR were analyzed by binary logistic regression and chi-square test. A p-value of &lt; 0.05 was considered statistically significant. Results: Of the 165 patients included, all were female, with a mean age of 50 and majority (97%) with invasive ductal carcinoma (IDC) histology. Baseline characteristics are summarized. 52 had hormone (HR)pos/Her2neg, 51 with triple negative, 47 had HR pos/Her2pos, and 15 had HR neg/Her2pos disease. pCR was seen in 36% of patients. A normal BMI of &lt; 25 (p=0.03), nonsmoker (p=0.01), grade III (p=0.01), HR pos/Her2pos (p=0.02), and HR neg/Her2pos (p=0.0001), were associated with pCR. In patients with triple negative breast cancer, the use of immunotherapy did not influence pCR (p = 0.0565). There were no differences based on age, race, menopausal status, stage, size, presence of LVI or DCIS or multifocal disease. In the 157 patients where Ki-67 was known, tumors with higher Ki-67 values of 30-49% and &gt; 50% achieved pCR compared to those with lower Ki-67 (p = 0.002). Conclusions: Those with normal BMI, non-smokers, and aggressive clinicopathological factors such as Her2 positive, higher Ki67 (30% and above), and grade III disease were more likely to achieve pCR after neoadjuvant systemic therapy. These findings further identify tumor characteristics most likely to respond to neoadjuvant chemotherapy. [Table: see text]

Low expression of Ki-67/MIB-1 labeling index in IDH wild type glioblastoma predicts prolonged survival independently by MGMT methylation status

PurposeThe Ki-67/MIB-1 labeling index (LI) is clinically used to differentiate between high and low-grade gliomas, while its prognostic value remains questionable. Glioblastoma (GBM) expressing wild-type isocitrate dehydrogenase IDHwt, a relatively common malignant brain tumor in adults, is characterized by a dismal prognosis. Herein, we have retrospectively investigated the prognostic role of Ki-67/MIB-1-LI in a large group of IDHwt GBM.MethodsOne hundred nineteen IDHwt GBM patients treated with surgery followed by Stupp’s protocol in our Institution between January 2016 and December 2021 were selected. A cut-off value for Ki-67/MIB-1-LI was used with minimal p-value based approach.ResultsA multivariate analysis showed that Ki-67/MIB-1-LI expression < 15% significantly correlated with a longer overall survival (OS), independently from the age of the patients, Karnofsky performance status scale, extent of surgery and O6-methylguanine (O6-MeG)-DNA methyltransferase promoter methylation status.ConclusionsAmong other studies focused on Ki-67/MIB-1-LI, this is the first observational study showing a positive correlation between OS of IDHwt GBM patients and Ki-67/MIB-1-LI that we propose as a new predictive marker in this subtype of GBM.

Clinical features and prognostic factors in 49 patients with follicular lymphoma at a single center: A retrospective analysis

Follicular lymphoma (FL) is a type of B-cell lymphoma that originates at the germinal center and has a low malignancy rate. FL has become the most common inert lymphoma in Europe and America but has a relatively low incidence in Asia. To explore the clinical features, curative effects, and prognostic factors of FL. Completed medical records of 49 patients with FL who were admitted to the Ningbo First Hospital from June 2010 to June 2021 were examined. These patients were definitively diagnosed by pathological biopsy or immunohistochemical staining. The diagnostic criteria were based on the 2008 World Health Organization classification of lymphomas. Ann Arbor staging was performed according to the imaging and bone marrow examination results. Risk stratification of all patients was performed based on the International Prognostic Index (IPI), age-adjusted IPI, Follicular Lymphoma International Prognosis Index (FLIPI), and FLIPI2 to compare the efficacy of different treatment regimens and analyze the related prognostic factors. The age of onset in patients ranged from 24 to 76 years, with a median age of 51 years. Most patients developed the disease at 40-59 years of age, and the male:female ratio was 1.6:1. No significant difference was noted in the curative effect between the non-chemotherapy, combined chemotherapy, and other chemotherapy regimens (P > 0.05). Hemoglobin (Hb) level < 120 g/L, Ki-67 value > 50%, bone marrow involvement, and clinical stages III-IV were associated with a poor prognosis of FL (P < 0.05). However, the influence of other indicators was not statistically significant. Risk grouping was performed using the FLIPI, and the results showed that 24.5%, 40.8%, and 34.7% of patients were in the low-, moderate-, and high-risk groups, respectively. According to the survival analysis results, the survival rate of patients was lower in the high-risk group than in the other low-risk and moderate-risk groups (P < 0.05). FL mainly occurs in middle-aged and elderly men, primarily affecting lymph nodes and bone marrow. Hb level, Ki-67 value, bone marrow involvement, and clinical staging were used to evaluate prognosis.

Surgical Interest of an Accurate Real-World Prediction of Primary Systemic Therapy Response in HER2 Breast Cancers

Human epidermal growth factor receptor 2 (HER2)-enriched breast cancers (BC) present the highest rates of pathological response to primary systemic therapy (PST), but they are also the ones that tend to be larger at diagnosis, with microcalcifications and, often, with axillary involvement. If we do not have a reliable method to predict the degree of response, we may not be able to transfer the benefits of PST to surgery. The post-PST surgery planning is guided by the findings in the magnetic resonance imaging (MRI), whose predictive capacity, although high, is far from optimal. Thus, it seems interesting to find other variables to improve it. A retrospective observational study including women with HER2 BC treated with PST and further surgery was conducted. Information regarding clinical, radiological, and histopathological variables was gathered from a total of 132 patients included. Radiological complete response (rCR) was achieved in 65.9% of the sample, and pathological complete response (pCR), according to Miller and Payne criteria, in 58.3% of cases. A higher Ki67 value, the absence of Hormonal Receptors expression, and an rCR was significantly related to a pCR finding. This information impacts directly in surgery planning, as it permits adjustment of the breast resection volume.

Stromal Ki67 Expression Might be a Useful Marker for Distinguishing Fibroadenoma From Benign Phyllodes Tumor of the Breast.

Background. Fibroadenoma (FA) and benign phyllodes tumor (PT) of the breast often have similar appearances on imaging. While an exact diagnosis of biopsy specimens is required to choose adequate treatment, including surgical procedures, it is sometimes difficult to pathologically differentiate these 2 tumors due to histological resemblances. To elucidate markers for distinguishing FA from benign PT, we analyzed clinical samples immunohistochemically. Methods. We retrospectively investigated 80 breast fibroepithelial lesions. As a discovery set, 60 surgical excision samples (30 FA and 30 benign PT) were examined. Twenty biopsy samples (10 FA and 10 benign PT) were examined as a validation set. To determine targets for immunohistochemistry, we first tested some proteins based on previous reports. As a result, Ki67 was chosen for differentiating FA and PT; thus further examinations were conducted with this protein. Results. Among the proteins examined, stromal Ki67 was significantly higher in PT than in FA. Benign PT had significantly higher stromal Ki67 expression both at random and at hotspots (p < .001 and <.001, respectively). The receiver operating characteristic curve analysis identified 3.5% and 8.5% (at random spots and hotspots, respectively) as the optimal cutoff values of stromal Ki67 for distinguishing between these 2 tumors. In the validation cohort employing needle biopsy specimens, we confirmed that these 2 cutoff values properly classified these 2 tumors (p = .043 and .029, respectively). Conclusion.We revealed that stromal Ki67 might be a potential marker for distinguishing FA from benign PT.

Recurrence and mortality rate in an Italian multi-center case series of parathyroid atypical adenomas and carcinomas.

There are few data regarding the clinical outcome of patients with parathyroid carcinoma (PC) and atypical adenoma (AA) after surgery. Aim of our study was to investigate disease recurrence and mortality rate as well as their predictors in a series of patients with PC or AA. Clinical and biochemical parameters, histological features, incidence of disease recurrence and mortality rate were retrospectively assessed in 39 patients (51% males, mean age 56.2 ± 17.2 years) diagnosed with PC (n=24) or AA (n=15) and followed up for 6.8 ± 5.0 years after surgery. No differences in baseline characteristics were registered between the two groups, except for higher KI67 values in PC than AA (6.9 ± 3.9% vs 3.4 ± 2.1%, p<0.01). Eight patients (21%) experienced recurrence after a mean follow-up of 5.1 ± 2.7 years, with higher relapse rate in PC than AA (25% vs 13%), though this difference did not reach statistical significance. Mortality rate was 10% in the whole sample, without significant differences between PC and AA. Relapsing cases had been undergone the most extensive surgery more frequently and they had a higher mortality rate in comparison to non relapsing patients (38% vs 6% and 38% vs 3%, respectively, p<0.03 for both). In comparison to survivors, deceased patients were submitted to the most extensive surgery more frequently (50% vs 9%), they were older (74.8 ± 4.6 vs 53.2 ± 16.3 years), and they had higher KI67 values (11.7 ± 4.9 vs 4.8 ± 2.8, p<0.03 for all comparisons). During seven-year follow-up after surgery, no significant differences in recurrence and mortality rate were observed between PC and AA patients. Death was associated with disease relapse, older age and higher KI67 values. These findings suggest a similar and careful long-term follow-up in both parathyroid tumors, especially in older patients, and emphasize the need of further studies in large cohorts to throw light on this crucial clinical issue.

63P Ki67 values and MammaPrint (MP) genomic risk in early breast cancer: Correlation by ductal vs lobular histology

In MINDACT trial, 4 risk categories (RC) by clinical (c) and genomic (g) breast cancer (BC) risk were defined. The study showed that the cHigh/gLow group without chemotherapy (CT) had a 94.8 % (CI 95% 92.9-96-2) 5-year Distant Metastases Free Survival (DMFS), so meeting the trial primary objective. Recently, a MP g group with excellent prognosis, named ultralow (gUL), has been described (15% in MINDACT). However, few data exist regarding the distribution of these 4 MINDACT RC and the proportion of gUL in the invasive lobular carcinoma (ILC) population. Moreover, association of Ki67 values and MP RC is rarely studied, both in general population and, particulary, in ILC pts. We aimed to address all these questions by comparing our series of invasive carcinoma of non-special type (NST) and ILC pts in whom MP was performed. Pts with ER+/PgR±/HER2- early BC diagnosed from 2012 to 2020 in our institution and with MP data were reviewed. Clinical risk was defined as in the MINDACT trial; genomic risk defined by MP score (UL score: 0.355 to 1.00). 152 pts were identified. NST: 85%, ILC: 15%. Median age NST/ICL: 54/59 years. Histological grade (HG) 1/2/3 (NST vs ILC) 19%/73%/8% and 18%/82%/0%, respectively. UL (g) risk: 17 (13.2%) in NST, 3 (13%) in ILC. The distribution of RC is summarized in the table [UL and Low-non-Ultralow (LNUL) combined for small numbers in ILC]. Median Ki67 value by (g) RC (gLow vs High) in the NST group were 12 and 20: (p<0.001). Of note, in ILC pts median Ki67 was 15 for both MP (g) RC (p=0.77). Table: 63POverall (n=151)NST (n=129)CLI (n=22)cLow-gLow (N/%)61 (40.4)51 (39.5)10 (45.5)cLow-gHigh (N/%)39 (25.8)36 (27.9)3 (13.6)cHigh-gLow (N/%)36 (23.8)28 (21.7)8 (36.3)cHigh-gHigh (N/%)15 (9.9)14 (10.8%)1 (4.5) Open table in a new tab Our results suggest a trend for lower genomic RC in ILC population compared to NST pts. As expected, median Ki67 values correlated with MP genomic categories in overall population and in NST but, intriguingly, not in ILC pts. The small number of pts in this latter group limits results. Further data in wider populations are needed to establish the true association of Ki67 with MP categories in ILC population.

Assessment of treatment response to dendritic cell vaccine in patients with glioblastoma using a multiparametric MRI-based prediction model.

Autologous tumor lysate-loaded dendritic cell vaccine (DCVax-L) is a promising treatment modality for glioblastomas. The purpose of this study was to investigate the potential utility of multiparametric MRI-based prediction model in evaluating treatment response in glioblastoma patients treated with DCVax-L. Seventeen glioblastoma patients treated with standard-of-care therapy + DCVax-L were included. When tumor progression (TP) was suspected and repeat surgery was being contemplated, we sought to ascertain the number of cases correctly classified as TP + mixed response or pseudoprogression (PsP) from multiparametric MRI-based prediction model using histopathology/mRANO criteria as ground truth. Multiparametric MRI model consisted of predictive probabilities (PP) of tumor progression computed from diffusion and perfusion MRI-derived parameters. A comparison of overall survival (OS) was performed between patients treated with standard-of-care therapy + DCVax-L and standard-of-care therapy alone (external controls). Additionally, Kaplan-Meier analyses were performed to compare OS between two groups of patients using PsP, Ki-67, and MGMTpromoter methylation status as stratification variables. Multiparametric MRI model correctly predicted TP + mixed response in 72.7% of cases (8/11) and PsP in 83.3% (5/6) with an overall concordance rate of 76.5% with final diagnosis as determined by histopathology/mRANO criteria. There was a significant concordant correlation coefficient between PP values and histopathology/mRANO criteria (r = 0.54; p = 0.026). DCVax-L-treated patients had significantly prolonged OS than those treated with standard-of-care therapy (22.38 ± 12.8 vs. 13.8 ± 9.5months, p = 0.040). Additionally, glioblastomas with PsP, MGMT promoter methylation status, and Ki-67 values below median had longer OS than their counterparts. Multiparametric MRI-based prediction model can assess treatment response to DCVax-L in patients with glioblastoma.

Meningiomlarda Ki-67 Proliferasyon İndeks Pozitiflik Sınır Değeri

Meningiomas are usually slow-growing grade 1 tumors according to World Health Organization (WHO) classification. Histological and molecular criterias were defined for the determination of meningiomas of high grade and more aggressive. The proliferation activity is also considered among histopathological criterias. A commonly used parameter for determining proliferation activity is the Ki-67 index. This study was formed retrospectively to identife the positivity limit (cut-off) value of the Ki-67 proliferation index in cases diagnosed with meningioma. The Ki-67 indices of a total 190 patients diagnosed with meningioma was compared with the histological degrees of the tumors. The ROC analysis method was used in the statistical analysis for Ki-67 values. The mean Ki-67 proliferation index was found to be 3% for grade 1, 8% for grade 2 and 17% for grade 3 in the cases diagnosed with meningioma in our center. The Ki-67 proliferation index, which can be used in addition to histopathological findings in the distinction of grade 1 and grade 2 meningiomas in our laboratory, was determined as a positivity limit value of 6,5 (p&amp;gt;0,05).

How successful is the volumetric ADC value in forecasting isocitrate dehydrogenase mutation status of adult-type diffuse glioma?

BackgroundGliomas are the most common central nervous system tumours. The 2021 fifth edition of the World Health Organization Classification of Tumors of the Central Nervous System introduced significant changes in molecular features of tumours such as IDH types. We aim to investigate the relationship between the ADC value measured in preoperative diffusion-weighted imaging and the IDH profile in patients diagnosed with adult-type diffuse glioma. Forty patients who were operated on for diffuse glioma were included in the study and were divided into two groups, 'wild-type' (group 1) and 'mutant-type' (group 2), according to their Isocitrate dehydrogenase (IDH) profiles based on The fifth edition (2021) of the World Health Organization Classification of Tumors of the Central Nervous System. Preoperative MRI images of the patients were evaluated for tumour side, location and apparent diffusion coefficient (ADC) values. In addition, ADC values were analysed and compared in both groups.ResultsThe mean age of the patients was 61.17 ± 14.24 years. Twenty-seven patients (67.5%) were diagnosed as IDH-wild tumours, and 13 (32.5%) patients were diagnosed as IDH-mutant. In comparison between the two groups, there was no statistical difference between ADCmean, ADCmin, ADCmax and Ki67 values (p:0.931; p:0.820; p:0.519 and p:0.159, respectively).ConclusionsIt is obvious that effective and minimally invasive measurements such as ADC will take part in managing intracranial tumours. However, in this technique, closely related to cellular intensity, it is not always possible to distinguish subtyping at the molecular level, such as IDH.

Clinico-pathologic relationships with Ki67 and its change with short-term aromatase inhibitor treatment in primary ER + breast cancer: further results from the POETIC trial (CRUK/07/015)

PurposeKi67 assessed at diagnosis (Ki67baseline) is an important prognostic factor in primary oestrogen receptor-positive (ER +) breast cancer. Proportional change in Ki67 after 2 weeks (∆Ki672week) is associated with clinical benefit from endocrine therapies and residual Ki67 (Ki672week) with recurrence-free survival. The aim was to define the association between Ki67baseline and after aromatase inhibitor (AI) exposure ∆Ki672week and Ki672week with key prognostic and biologic factors utilising data from the POETIC study.Patients and methodsIn POETIC 4480 postmenopausal patients with primary ER and/or PgR + breast cancer were randomised 2:1 to 2 weeks’ presurgical AI (anastrozole or letrozole) or no presurgical treatment (control). Ki67 was measured centrally in core-cut biopsies taken prior to AI and in core-cuts or the excision biopsy at surgery. Relationships between the Ki67 and biologic factors were explored using linear regression.ResultsEstablished associations of Ki67baseline with biologic factors including PgR status, tumour grade, tumour size, histological subtype, nodal status, and vascular invasion were confirmed in the HER2- subpopulation. In the HER2 + subpopulation only grade and tumour size were significantly associated with Ki67baseline. In control group Ki672week was 18% lower than Ki67baseline (p < 0.001) when Ki672week was measured in excision biopsies but not when measured in core-cuts. Median suppression by AIs (∆Ki672week) was 79.3% (IQR: −89.9 to −54.6) and 53.7% (IQR: −78.9 to −21.1) for HER2-negative and HER2-positive cases, respectively. Significantly less suppression occurred in PgR- vs PgR + and HER2 + vs HER2- tumours which remained apparent after adjustment for 2-week sample type.ConclusionsThe magnitude of this study allowed characterisation of relationships between Ki67baseline, ∆Ki672week and Ki672week with high degrees of confidence providing a reference source for other studies. Lower values of Ki67 occur when measured on excision biopsies and could lead to apparent but artefactual decreases in Ki67: this should be considered when either ∆Ki672week or Ki672week is used in routine clinical practice to aid treatment decisions or in clinical trials assessing new drug therapies.

Expression levels of Ki-67 and cyclin D1 in advanced nasopharyngeal carcinoma and its prognosis

Introduction and Aim: Nasopharyngeal cancer (NPC) prognosis has been associated with cyclin D1 and Ki-67. These tumor markers had never been tested in NPC patients in Indonesia before. Therefore, this study aims to evaluate the relationships between Ki-67 and cyclin D1 expression levels and the clinicopathological features of nasopharyngeal cancer (NPC) patients. Materials and Methods: During the years 2015 until 2018, thirty-one nasopharyngeal cancer patients were studied in a cohort study at RSUPN Dr. Cipto Mangunkusumo. Patients aged 18 years, diagnosed with NPC according to the histopathological results, metastasis NPC, Eastern Cooperative Oncology Group 0–1, and those who had completed first-line chemotherapy treatment with 5–fluorouracil were included in this study. The Ki-67 and cyclin D1 expression levels were evaluated with the h-score. The NLR values were collected prior to the treatment. The 2-year survival rate was analyzed based on the optimal cut-off value obtained. The optimal cut-off values of Ki-67 and cyclin D1 were categorized into high- and low-expression groups to observe the 2-year mortality. Results: The relationships between Ki-67 and cyclin D1, clinical, pathological, and prognosis of patients were examined. Patients with Ki-67 high expression had a worse 2-year survival rate than those with low expression (p0.05). Ki-67 expression was found to be significantly related to adverse outcomes (p0.05, OR: 41.107, 95% CI: 2.600–649.940), while the cyclin D1 expression was not significantly related to adverse outcomes (p0.05). Conclusion: Ki-67 expression was associated with poor prognosis in NPC patients. Nevertheless, further research is required to explore the specific mechanism of cyclin D1 expression in NPC prognosis.

Intrathyroid thymic carcinoma: clinicopathological features and whole exome sequencing analysis.

Intrathyroid thymic carcinoma (ITC) is a rare malignant tumour. We present nine cases of ITC that were analysed by immunohistochemical staining, of which five were analysed using whole exome sequencing (WES). These cases included six women and three men with an age range of 31-66years. The average postoperative follow-up term was 37.8months (range, 7-95months), and all patients survived well except for one case with lung metastasis. Microscopically, ITC showed solid islands of tumour cells separated by fibrous connective tissue containing lymphocytes and other inflammatory cells. Tumour cells strongly expressed Ckpan (AE1/AE3), P63, and CD117. And all cases but one were positive for CD5. The median value of Ki-67 was 32% (range 10-60%). We observed partial positivity of Syn and CgA in only one case. ITC shares morphological and immunohistochemical similarities with thymic squamous cell carcinoma. In situ hybridization of EBER showed negative results. All cases were microsatellite stable, and the tumour mutational burden of the 5 cases was all < 1 mutations/Mb. WES showed higher mutation rates for N4BP1 (2/5), and many genetic alterations were related to the NF-kB signalling pathway, which is crucial for insight into the molecular mechanisms of the occurrence and development of ITC.