High Level Of Ki-67 Expression Research Articles

Evaluation of Ki67 Biomarker as a Prognostic Marker in Breast Invasive Ductal Carcinoma in Khartoum State in Sudan

Introduction: Worldwide, breast cancer is the most prevalent cancer among women to be diagnosed, and it is the primary cause of cancer-related mortality, coming in second only to lung cancer. High levels of Ki67, a nuclear marker of cell proliferation, in breast cancer are linked to worse outcomes. Methods and materials: This retrospective cross-sectional laboratory investigation aimed to examine Ki67 expression as a prognostic predictor in invasive ductal carcinoma (IDC) utilizing manual tissue microarrays (MTMAs) technology. The study was done from June 2018 to July 2019 at the Elrahman Health Centre in Khartoum, Sudan, using thirty-five paraffin block samples collected from patients previously diagnosed with invasive ductal carcinoma (IDC). The study population ranged in age from 31 to 71 years. Results: The study found that 94.3% (n=33/35) of the tissues were positive for the Ki67 antigen, while 5.7% (n=2/35) were negative. Age and score correlation is (P=0.047), and a favorable prognosis could be the cause of the two unfavorable results. Conclusion: This study highlights the importance of the Ki67 biomarker as a prognostic indicator in invasive ductal carcinoma (IDC) of the breast. High levels of Ki67 expression (94.3%) were associated with more aggressive tumors and poorer prognostic outcomes. However, there was no significant correlation between Ki67 scores and patient age, indicating age does not influence the prognostic value of Ki67 in this cohort.

Prediction of Ki-67 expression in bladder cancer based on CT radiomics nomogram.

This study aimed to create and validate a radiomics nomogram for non-invasive preoperative Ki-67 expression level prediction in patients with bladder cancer (BCa) using contrast-enhanced CT radiomics features. A retrospective analysis of 135 patients was conducted, 79 of whom had high levels of Ki-67 expression and 56 of whom had low levels. For the dimensionality reduction analysis, the best features were chosen using the least absolute shrinkage selection operator and one-way analysis of variance. Then, a radiomics nomogram was created using multiple logistic regression analysis based on radiomics features and clinical independent risk factors. The performance of the model was assessed using the Akaike information criterion (AIC) value, the area under the curve (AUC) value, accuracy, sensitivity, and specificity. The clinical usefulness of the model was assessed using decision curve analysis (DCA). Finally, to establish a radiomics nomogram, the best 5 features were chosen and integrated with the independent clinical risk factors (T stage) and Rad-score. This radiomics nomogram demonstrated significant correction and discriminating performance in both the training and validation sets, with an AUC of 0.836 and 0.887, respectively. This radiomics nomogram had the lowest AIC value (AIC = 103.16), which was considered to be the best model. When compared to clinical factor model and radiomics signature, DCA demonstrated the more value of the radiomics nomogram. Enhanced CT-based radiomics nomogram can better predict Ki-67 expression in BCa patients and can be used for prognosis assessment and clinical decision making.

A Study of Ki-67 Immunostaining in Prostate Carcinomas and Its Correlation with Gleason's Score and Prognosis: An Experience at a Tertiary Centre in the Himalayan Foothills.

Prostate cancer is a significant cause of cancer-related mortality among men worldwide, necessitating the exploration of prognostic biomarkers to aid in accurate risk assessment and treatment decision-making. This cross-sectional study aimed to comprehensively evaluate the role of Ki-67 as a prognostic marker in prostate cancer by examining its association with clinicopathological parameters. A total of 102 archived cases of prostate core biopsy specimens, histopathologically reported as prostate carcinoma, were included in this study. Histopathological grading was conducted using Gleason's scoring and grading system based on morphology. The statistical software "R" was utilized for data analysis. Kruskal-Wallis test and Fisher's exact test were employed to analyze the association between Ki-67 expression and clinicopathological parameters. The study revealed significant correlations between Ki-67 expression and various clinicopathological parameters in prostate cancer cases. High Ki-67 expression levels were associated with higher Gleason scores, increased incidence of perineural invasion, advanced T stages, lymph node metastasis, presence of distant metastasis, and higher prognostic stage groups. The findings of this cross-sectional study support the potential of Ki-67 as a prognostic marker in prostate cancer. The significant associations observed between Ki-67 expression and clinicopathological parameters indicate its usefulness in risk stratification and treatment decision-making. The incorporation of histopathological grading, including Gleason scoring, and analysis of perineural invasion strengthens the validity of the study. Ki-67, in combination with morphological assessments, provides valuable prognostic information for prostate cancer patients.

Quantitative parameters in novel spectral computed tomography for assessing gastric cancer and cell proliferation

ObjectivesTo investigate the diagnostic ability of novel spectral CT-derived parameters for gastric cancer histological types and Ki-67 expression. MethodsA total of 72 patients with histologically proven gastric cancer (GC) were retrospectively included in this study. All patients underwent dual-phase enhanced abdominal spectral CT. The arterial (AP) and venous phase (VP) slope of the spectral curve (λHU), iodine concentration (IC), normalized IC (NIC), effective atomic number (Zeff) and iodine-no-water concentration were retrospectively compared between patients with low and high Ki-67 expression levels and with different histological types in GC patients. The ROI was outlined independently by two senior physicians, and the average of three measurements at the largest level was taken. In addition, interobserver reproducibility was assessed by Bland-Altman analysis. Correlations between quantitative parameters and Ki-67 expression levels were assessed by Spearman's correlation coefficients. ResultsThe values between the mucinous group and nonmucinous carcinoma group were significantly different in both phases. The IC, NIC, and iodine-no-water concentration in the VP were significantly different among the Ki-67_L, Ki-67_M, and Ki-67_H groups. Spearman rank correlation analysis demonstrated a positive correlation between Ki-67 expression levels and IC, NIC, and iodine-no-water concentration in the VP, with correlation coefficients of 0.304, 0.424, and 0.322, respectively. ConclusionQuantitative spectral parameters can discriminate between low and high Ki-67 expression and different histological types in GC. The NIC, IC and iodine-no-water concentration can be useful parameters for evaluating of Ki-67 expression levels.

Conventional Tools for Predicting Satisfactory Response to Neoadjuvant Chemotherapy in HR+/HER2− Breast Cancer Patients

Aim: The aim of the study was to assess the role of Magee Equation 3 (MagEq3), IHC4 score, and HER2-low status in predicting “satisfactory response (SR)” to neoadjuvant chemotherapy (NAC) in HR+/HER2− breast cancer (BC) patients. Methods: In a retrospective study, female patients of any age with T_1–4, N_0–2, M₀ HR+/HER2− BC who received NAC and underwent adequate locoregional surgical treatment were included. Patients were grouped according to 2 outcomes: (a) overall response to NAC in breast and axilla by using residual cancer burden (RCB) criteria and (b) axillary downstaging after NAC by using N staging. 2 cohorts for overall response were overall SR (RCB 0–1) and no SR (RCB 2–3). On the other hand, for axillary downstaging, 2 cohorts constituted from axillary SR (ypN₀ and ypN_0i+) and no SR (ypN_mic-N3). MagEq3 and IHC4 scores were calculated from their pathological tumor slides in each patient. HER2 status was categorized as either “no” or “low.” In addition, patient age, family history, tumor histology, stage at admission, and Ki-67 status were compared between cohorts according to predefined outcomes. Results: In a total of 230 BC patients, 228 patients were included to compare according to their RCB levels. The mean age of patients with overall SR was significantly lower than those without. Patients with high Ki-67 expression, high (>30) MagEq3 score, high ICH4 quartile, and HER2-low status had significantly more overall SR. On the other hand, only patients with high Ki-67 expression had significantly more axillary SR. MagEq3 score levels, ICH4 quartiles, and HER2 status were similar between patients with axillary SR and not. Conclusion: MagEq3 and IHC4 tools seemed to be useful to predict those HR+/HER2− BC patients who are most likely to get benefit from NAC. But, only high Ki-67 expression level significantly predicted satisfactory axillary downstaging in HR+/HER2− BC patients.

Development of an ultrasound-based radiomics nomogram to preoperatively predict Ki-67 expression level in patients with breast cancer.

ObjectiveTo develop and validate a radiomics nomogram that could incorporate clinicopathological characteristics and ultrasound (US)-based radiomics signature to non-invasively predict Ki-67 expression level in patients with breast cancer (BC) preoperatively.MethodsA total of 328 breast lesions from 324 patients with BC who were pathologically confirmed in our hospital from June 2019 to October 2020 were included, and they were divided into high Ki-67 expression level group and low Ki-67 expression level group. Routine US and shear wave elastography (SWE) were performed for each lesion, and the ipsilateral axillary lymph nodes (ALNs) were scanned for abnormal changes. The datasets were randomly divided into training and validation cohorts with a ratio of 7:3. Correlation analysis and the least absolute shrinkage and selection operator (LASSO) were used to select the radiomics features obtained from gray-scale US images of BC patients, and each radiomics score (Rad-score) was calculated. Afterwards, multivariate logistic regression analysis was used to establish a radiomics nomogram based on the radiomics signature and clinicopathological characteristics. The prediction performance of the nomogram was assessed by the area under the receiver operating characteristic curve (AUC), the calibration curve, and decision curve analysis (DCA) using the results of immunohistochemistry as the gold standard.ResultsThe radiomics signature, consisted of eight selected radiomics features, achieved a nearly moderate prediction efficacy with AUC of 0.821 (95% CI:0.764-0.880) and 0.713 (95% CI:0.612-0.814) in the training and validation cohorts, respectively. The radiomics nomogram, incorporating maximum diameter of lesions, stiff rim sign, US-reported ALN status, and radiomics signature showed a promising performance for prediction of Ki-67 expression level, with AUC of 0.904 (95% CI:0.860-0.948) and 0.890 (95% CI:0.817-0.964) in the training and validation cohorts, respectively. The calibration curve and DCA indicated promising consistency and clinical applicability.ConclusionThe proposed US-based radiomics nomogram could be used to non-invasively predict Ki-67 expression level in BC patients preoperatively, and to assist clinicians in making reliable clinical decisions.

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

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

Prognostic value of tumor-infiltrating lymphocytes in estrogen receptor-positive and human epidermal growth factor receptor 2-negative breast cancer.

Tumor-infiltrating lymphocytes (TILs) are a significant prognostic factor in triple-negative breast cancer. However, the clinicopathological significance of TILs in estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer remains unclear. The purpose of the present study was to evaluate the role of TILs in the prognosis of ER-positive and HER2-negative breast cancer. A total of 65 consecutive patients with ER-positive and HER2-negative breast cancer were examined. TILs in stromal tissue (str-TILs) were graded using the International TILs Working Group criteria. The association between several clinicopathological factors and TIL grade were investigated, and the prognostic impact of TILs was compared between luminal A-like and luminal B-like breast cancer. A total of 51 patients (78.5%) had low-grade (0-10%), 11 (16.9%) had intermediate (10-40%) and 3 (4.6%) had high-grade (40-90%) str-TIL levels. There was a significant association between high levels of Ki67 expression and a high str-TIL count. Relapse-free survival was significantly worse in patients with luminal B-like cancer compared with that in patients with luminal A-like cancer. Patients with an intermediate or high str-TIL count had a better prognosis compared with those with a low str-TIL count. All patients with luminal B-like cancer and intermediate or high str-TIL levels developed no recurrence during follow-up. In conclusion, there was a significant correlation between high-grade str-TIL levels and high tumor cell proliferation rate, as well as high levels of Ki67 expression.

Ki-67 proliferative index correlation to the immunohistochemistry profile in early female breast cancer: a review of 515 cases

Introduction: Many biological markers are used as prognostic and predictive indicators in invasive breast cancers management. Among them, tumour size, grade, patho-morphological subtype, hormone receptors status and HER2 receptor expression in addition to Ki-67 proliferative index. Also, they play a key role in adjuvant treatment decision making. Our aim was to evaluate the association between Ki-67 proliferative index and breast cancer immunological subtype. Material and methods: A total of 515 early invasive patients were enrolled, tumour biological characteristics as histopathological subtype, immune-histo-chemistry (ER,PR,HER2) status and Ki-67 proliferation index values have been collected. The Ki-67 index level of 20%, was used as the cut-off point to differentiate between low and high Ki-67 expression levels. Statistical analysis has been performed using the Chi square test online tool. Results: In this cohort, about 42%, 33%, 7%, and 18% of the cases were grouped as luminal A-like, luminal B-like, HER2 enriched subtype, and triple-negative, respectively. All luminal A-like patients had Ki-67 level less than 20%. About 3% of the cohort, are luminal B-like tumours with Ki-67 level less than 20%, where 30.3% of the patients were luminal B-like tumours with Ki-67 level ≥ 20%. In HER2 enriched subtype, Ki- 67 of < 20% level seen in 1.9% of cases, and Ki-67 levels ≥ 20% was observed in 5.2% of the cases. In the triple-negative group, Ki-67 was 20% or higher in 16% of cases, and only 1.7% of patients had Ki-67 level less than 20%. Conclusion: Luminal A-like tumours were the most frequently encountered subtype, they have low Ki-67 levels and are known to be of a low histological grade tumour, and usually associated with a good prognosis. Also, data indicates that high Ki-67 levels are seen more often in Luminal B-Like breast cancers as well as in triple-negative breast cancers and HER2 enriched tumours.

Analysis of the Predictive Value of EZH2 Expression Level on the Clinical Efficacy and Long-term Prognosis of Patients with Primary Gastrointestinal Diffuse Large B-cell Lymphoma

To investigate the predictive value of methyltransferase EZH2 expression level on the clinical efficacy and long-term prognosis of patients with primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL). 161 patients with newly treated PGI-DLBCL in our hospital from August 2013 to July 2019 were selected. The expression level of EZH2 protein was detected by immunohistochemistry, and the short-term efficacy and long-term survival differences of patients with different levels of EZH2 were compared. The predictive values of EZH2 expression level on the short-term efficacy and long-term prognosis of PGI-DLBCL patients were analyzed by Log-rank test and COX risk proportional regression model. Chi-square test and Logistic regression analysis were used to analyze the influencing factors of EZH2 expression level. The complete response (CR) and overal response(OR) rates of those with high EZH2 expression were significantly lower than those with low EZH2 expression (P<0.001). The median OS and PFS of EZH2 high-level and low-level expression group was 37, 31 months and 49, 42 months, respectively. The cumulative OS and PFS rates of the high-level expression group were significantly lower than those of the low-level expression group, and the differences were statistically significant (P<0.05). The high expression levels of H3K27me3, EZH2, BCL-2, BCL-6, c-MYC were closely related to the shortening of OS and PFS, while the high expression level of Ki-67 was closely related to the shortening of OS (P<0.05), of which the high expression levels of H3K27me3, EZH2, BCL-2, and BCL-6 were independent risk factors for shortening of OS and PFS. The expression level of EZH2 was positively correlated with the expression level of H3K27me3, BCL-6, c-MYC and Ki-67 (r=0.741, r=0.837, r=0.809, r=0.772), and the high expression levels of H3K27me3, BCL-6 and Ki-67 were independent factors influencing the high expression of EZH2. In patients with PGI-DLBCL, the high expression of EZH2 significantly reduces the short-term CR and OR rates, which is an independent risk factor for the shortening of long-term OS and PFS rates, and it is independently related to the high expression of H3K27me3 and BCL6.

Brown adipose tissue (BAT) activation at 18F-FDG PET/CT: correlation with clinicopathological characteristics in breast cancer

BackgroundThere is conflicting results of few published human 18F-FDG PET/CT studies about BAT activation in breast cancer (BC). The aim of the study is to evaluate the association between the levels of BAT metabolic activity detected by 18F-FDG PET/CT and clinicopathological characteristics of a tumor in patients with primary BC.ResultsBAT was activated in 16 out of 157 (10.2%) consecutive female patients with BC who underwent 18F-FDG PET/CT for initial evaluation. The majority of patients (15/16) had bilateral uptake in the supraclavicular regions. The mean values of the highest SUVmax and total metabolic activity (TMA) of activated BAT were 13.3 ± 9.9 and 79.6 ± 45, respectively. Median outdoor temperature was significantly lower in the activated BAT group (P value=0.035). Patients with BAT activation tended to have a lower median primary tumor size and primary SUVmax, but not statistically significant than those without BAT activation. BAT activation was significantly more frequent among younger age groups (14/16) and patients with lower body mass index (BMI) (10/16), but it was insignificantly more frequent among estrogen receptor-positive (ER+), progesterone receptor-positive (PR+), human epidermal growth factor receptor2 negative (HER2-), invasive ductal carcinoma (IDC), grade II, luminal B subtype, high Ki-67 expression level, patients with positive nodal metastasis, and in patients without distant metastasis. TMA was significantly higher among HER2+ patients (P value=0.019), but insignificantly higher among the younger age groups, stages I and II, invasive lobular carcinoma (ILC), grade I, luminal B subtype, ER+, PR−, higher Ki-67 expression level, patients with positive nodal, and distant metastasis. BMI and patient’s age were the significant independent predictor factors for BAT activation on multivariate regression analysis.ConclusionBAT activation in young age females is sex hormone-dependent, positively associated with less aggressive molecular subtypes of BC, less frequent in patients with distant metastasis. BAT activation may be a prognostic factor that carries a better prognosis in BC.

Prognostic and clinical significance of focal adhesion kinase expression in breast cancer: A systematic review and meta-analysis.

BackgroundThe prognostic significance of focal adhesion kinase (FAK) in breast cancer remains controversial. Here, we conducted a meta-analysis to explore the prognostic value of FAK expression in breast cancer.Materials and methodsPossible prognostic significance of protein or mRNA expression of FAK in breast cancer was investigated with searches of electronic databases for relevant publications. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were extracted from eligible studies.ResultsA total of eight eligible studies which included 2604 participants were analyzed in this meta-analysis. Increased expression of FAK protein was found to significantly correlate with shorter overall survival (OS) (HR = 1.43, 95% CI: 1.12–1.83; P = 0.004), and not with disease-free survival (HR = 1.31, 95% CI: 0.92–1.85; P = 0.14). Elevated FAK protein expression was also associated with negative estrogen receptor (ER) expression (OR, 1.34; 95% CI, 1.06–1.68; P = 0.01), negative progesterone receptor (PR) expression (OR, 1.54; 95% CI, 1.22–1.93; P < 0.001), positive human epidermal growth factor receptor 2 (HER2) expression (OR, 1.64; 95% CI, 1.28–2.09; P < 0.001), triple-negative breast cancer (TNBC) (OR, 1.57; 95% CI, 1.14–2.17; P = 0.006), high nuclear grade (OR, 1.70; 95% CI, 1.05–2.78; P = 0.03), high Ki-67 expression level (OR, 2.87; 95% CI, 1.94–4.24; P < 0.001), and positive p53 status (OR, 2.28; 95% CI, 1.58–3.29; P < 0.001).ConclusionOur meta-analysis identifies an association between increased FAK protein expression and worse OS among breast cancer patients. Moreover, enhanced FAK expression is associated with negative ER expression, negative PR expression, positive HER2 expression, TNBC, high nuclear grade, high Ki-67 expression level, and positive p53 status in breast carcinoma.

115P - Expression of Ki-67 as a prognostic factor in patients with colorectal cancer

BackgroundColorectal cancer is in fourth place due to mortality worldwide. In order to improve the diagnosis of colorectal cancer, immunohistochemical studies are becoming increasingly popular. The available literature contains a number of publications devoted to the study of the prognostic value of the expression of various biomarkers. However, the value of expression levels of the proliferation marker Ki-67 in colorectal cancer remains poorly understood. In this regard, the purpose of our study was to study the clinical significance of the expression of Ki-67 as a prognostic factor in patients with colorectal cancer. MethodsTo study the clinical significance of the expression of Ki-67 as a prognostic factor in patients with colorectal cancer, we examined 201 patients with colorectal cancer who were undergoing surgical treatment in combination with chemotherapy. ResultsA study of the proliferative activity of tumor glandular epithelial cells using patient Ki-67 proliferation marker showed that low or medium expression level (≤ 30%) was observed in 138 (68.9%) patients, while high (> 30%) - in 63 patients (31.1%). Binary logistic regression made it possible to establish links between the expression level of Ki-67 and the tumor stage, the presence of metastases in regional lymph nodes, the presence of distant metastases and the degree of tumor differentiation. In particular, patients with stage II, III, and IV stages of cancer had a higher chance of having a high level of Ki-67 expression than patients with stage I disease — 2.63, 3.16, and 3.97 times, respectively. The presence of 4 or more regional lymph nodes (N2) was accompanied by higher chances (6.6 times) to have a high level of expression of Ki-67, and the presence of distant metastases (M1) - by 1.92 times. Patients with low-differentiated cancer had a 5.1- times higher chance of being in the group with a high level of Ki-67 expression than patients with highly differentiated cancer. ConclusionsThe results of the research on finding the most informative and effective methods for predicting and diagnosing colorectal cancer among residents of the studied region will allow developing and introducing methods for complex primary and secondary prevention. Legal entity responsible for the studyThe author. FundingHas not received any funding. DisclosureThe author has declared no conflicts of interest.

Prognostic effect of Ki-67 in common clinical subgroups of patients with HER2-negative, hormone receptor-positive early breast cancer.

Several clinical trials have investigated the prognostic and predictive usefulness of molecular markers. With limited predictive value, molecular markers have mainly been used to identify prognostic subgroups in which the indication for chemotherapy is doubtful and the prognosis is favorable enough for chemotherapy to be avoided. However, limited information is available about which groups of patients may benefit from additional therapy. This study aimed to describe the prognostic effects of Ki-67 in several common subgroups of patients with early breast cancer. This retrospective study analyzed a single-center cohort of 3140 patients with HER2-, hormone receptor-positive breast cancer. Five-year disease-free survival (DFS) rates were calculated for low (< 10%), intermediate (10-19%), and high (≥ 20%) Ki-67 expression levels, as assessed by immunohistochemistry, and for subgroups relative to age, body mass index, disease stage, tumor grade, and (neo-)adjuvant chemotherapy. It was also investigated whether Ki-67 had different effects on DFS in these subgroups. The 5-year DFS rates for patients with low, intermediate, and high levels of Ki-67 expression were 0.90, 0.89, and 0.77, respectively. Ki-67 was able to further differentiate patients with an intermediate prognosis into different prognostic groups relative to common clinical parameters. Patients with stage II breast cancer had 5-year DFS rates of 0.84, 0.88, and 0.79 for low, intermediate, and high levels of Ki-67 expression. Ki-67 had different prognostic effects in subgroups defined by age and tumor grade. Ki-67 may help identify patients in intermediate prognostic groups with an unfavorable prognosis who may benefit from further therapy.

The clinicopathological analysis of receptor tyrosine kinases in meningiomas: the expression of VEGFR-2 in meningioma was associated with a higher WHO grade and shorter progression-free survival.

WHO grade II/III meningiomas recur frequently and there is currently no established molecular target therapy for meningioma. No previous studies have revealed the association between receptor tyrosine kinases (RTKs) and the recurrence of meningiomas. This study aims to elucidate the association between RTKs and the clinicopathological characteristics and recurrence of meningioma. We investigated the immunohistochemical expression of RTKs (VEGFR-1/2/3, PDGFR-alpha/beta and c-Kit) in 81 meningiomas (WHO grade I, n = 64, WHO grade II/III, n = 17) in 74 patients. Immunohistochemistry revealed that 29 WHO grade I (45%), 10 WHO grade II (77%), and 4 WHO grade III (100%) tumors were VEGFR-2-positive, and that the VEGFR-2 expression was significantly correlated with the WHO grade. In univariate analyses to investigate the clinicopathological factors associated with recurrence, Simpson grade IV/V resection, a larger tumor size, a high VEGFR-2 expression level, WHO grade II/III, a high Ki-67 expression level, and the non-expression of PgR were identified as significant factors. Furthermore, patients with VEGFR-2-positive meningiomas showed significantly shorter progression-free survival. In the multivariate analysis, WHO grade II/III and the location were significantly associated with recurrence. In conclusion, our study suggests that VEGFR-2 inhibitors might be one of the best candidates for molecular therapy against recurrent meningiomas.

Prognostic Value of the PRAME Gene Expression in T-Cell Lymphoproliferative Disorders

Background. T-cell lymphomas (T-CL) represent a heterogeneous group of malignant lymphoproliferative disorders characterized by unfavorable prognosis. The cancer-testis PRAME gene is notable for its spontaneous expression in transformed cells as observed in solid tumors, B-cell lymphoproliferative and chronic myeloproliferative diseases. Activity and clinical significance of PRAME in T-CL was not studied before, which determines the relevance and provides ground for the present trial. Aim. To assess the clinical significance of the PRAME gene expression in T-CL. Materials &amp; Methods. PRAME gene expression level was measured in samples of lymph nodes, blood, and bone marrow from 35 T-CL patients. Among them 3 patients received allogeneic hematopoietic stem cell transplantation, and 6 patients received autologous hematopoietic stem cell transplantation. A correlation was established between the PRAME expression in bone marrow and peripheral blood with morphological markers of disseminated disease with bone marrow lesions and leukemic blood. PRAME expression level was correlated with survival parameters and tumor proliferative activity (Ki-67). Results. PRAME activity was observed in 21 (60 %) patients. PRAME hyperexpression is associated with advanced stages of disease (p = 0.0734), bone marrow lesions (p = 0.0289), leukemic blood (p = 0.0187), worsening of the overall survival (OS) (p = 0.0787) and event-free survival (EFS) (p = 0.7185), also after hematopoietic stem cell transplantation (p = 0.2661 for OS and p = 0.0452 for EFS), and with a high Ki-67 expression level (p = 0.0155). Conclusion. PRAME expression in T-CL is often observed and related with unfavorable clinical prognosis.

Development of a radiomics signature to predict Ki-67 expression level in non-small cell lung cancer

To develop a radiomics signature based on CT image features to estimate the expression level of Ki-67 in non-small cell lung cancer (NSCLC). Methods: A total of 108 NSCLC patients, who underwent non-enhanced and contrast-enhanced CT scan in our hospital from January 2014 to November 2017, were retrospectively analyzed. They were confirmed by histopathological examination and undergone Ki-67 expression level test within 2 weeks after CT examination. The non-enhanced and contrast-enhanced CT three-dimensional structural images of the lesions were manually delineated by MaZda software, and the texture features of the region of interest were extracted. Combination of feature selection and classification methods were used to build radiomics signatures, and the classification were assessed using misclassification rates. The MaZda software provides texture feature selection methods including mutual information (MI), Fisher coefficients (Fisher), classification error probability combined with average correlation coefficients (POE+ACC), and Fisher+POE+ACC+MI (FPM), and texture feature analysis including raw data analysis (RDA), principal component analysis (PCA), linear classification analysis (LDA) and nonlinear classification analysis (NDA). Results: Among the 108 patients, 50 cases were at high levels of Ki-67 expression and 58 cases were at low levels of Ki-67 expression, respectively. The differences of gender, age and pathological type between the two groups were statistically significant (P<0.05). The radiomics signature built by FPM feature selection combined with NDA feature analysis based on non-enhanced CT images achieved the best performance for predicting the level of Ki-67 with a misclassification rate of 14.81%. However, radiomics signature based on contrast-enhanced CT images did not reduce the misclassification rate. Conclusion: The radiomics signature based on conventional CT image texture features is helpful to predict the expression of Ki-67 in NSCLC lesions, which can provide a non-invasive technique for assessing the invasiveness and prognosis for NSCLC.

Role of dynamic contrast-enhanced MRI in evaluating the association between contralateral parenchymal enhancement and survival outcome in ER-positive, HER2-negative, node-negative invasive breast cancer.

Background parenchymal enhancement (BPE) on dynamic contrast-enhanced (DCE)-MRI has been associated with breast cancer risk, both based on qualitative and quantitative assessments. To investigate whether BPE of the contralateral breast on preoperative DCE-MRI is associated with therapy outcome in ER-positive, HER2-negative, node-negative invasive breast cancer. Retrospective. In all, 289 patients with unilateral ER-positive, HER2-negative, node-negative breast cancer larger than 5 mm. 3T, T1 -weighted DCE sequence. BPE of the contralateral breast was assessed qualitatively by two dedicated radiologists and quantitatively (using region-of-interest and automatic breast segmentation). Cox regression analysis was used to determine associations with recurrence-free survival (RFS) and distant metastasis-free survival (DFS). Interobserver variability for parenchymal enhancement was assessed using kappa statistics and intraclass correlation coefficient (ICC). The median follow-up time was 75.8 months. Multivariate analysis showed receipt of total mastectomy (hazard ratio [HR]: 5.497) and high Ki-67 expression level (HR: 5.956) were independent factors associated with worse RFS (P < 0.05). Only a high Ki-67 expression level was associated with worse DFS (HR: 3.571, P = 0.045). BPE assessments were not associated with outcome (RFS [qualitative BPE: P = 0.75, 0.92 for readers 1 and 2; quantitative BPE: P = 0.38-0.99], DFS, [qualitative BPE: P = 0.41, 0.16 for readers 1 and 2; quantitative BPE: P = 0.68-0.99]). For interobserver variability, there was good agreement between qualitative (κ = 0.700) and good to perfect agreement for most quantitative parameters of BPE. Contralateral BPE showed no association with survival outcome in patients with ER-positive, HER2-negative, node-negative invasive breast cancer. A high Ki-67 expression level was associated with both worse recurrence-free and distant metastasis-free survival. 3 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2018;48:1678-1689.

The clinical observation of human papillomavirus positive breast tumor

In this manuscript, a unique case of HPV16-positive breast cancer is examined. The presence of HPV infection in the tumor is confirmed by two independent methods (PCR and immunohistochemistry). It is shown that in the presence of adverse factors of prognosis (lymphogenous metastasis, high level of Ki67 expression, presence of chromotrypsis in the tumor, and high level of genetic instability), a patient with a HPV-positive breast tumor has more than 8-year disease-free survival.

Prevalence and Prognostic Role of PIK3CA/AKT1 Mutations in Chinese Breast Cancer Patients.

PurposeThe prevalence of PIK3CA in Chinese breast cancer patients may be underestimated. Therefore, we investigated the distribution of somatic PIK3CA/AKT1 mutations in Chinese breast cancer patients and explored their roles in tumor phenotypes and disease prognosis.Materials and MethodsTumors from 507 breast cancer patients were prospectively collected from the West China Hospital between 2008 and 2013. Whole exons of AKT1 and PIK3CA were detected in fresh-frozen tumors using next-generation sequencing, and correlations between PIK3CA/AKT1 mutations and clinicopathological features were analyzed.ResultsThe AKT1 mutation was found in 3.6% (18/507) of patients. Tumors from patients that carried the AKT1 mutation were estrogen receptor (ER)+/progesterone receptor (PR)+/human epidermal growth factor receptor 2 (HER2)‒ and were more likely to have high expression levels of Ki67. The prevalence of the PIK3CA mutation was 46.5% (236/507), and 35 patients carried two or three variants of the PIK3CA gene. PIK3CA mutations were associated with ER+/PR+/HER2‒ status. The prognosis of patients with one mutation in PIK3CA (or PIK3CA/AKT1) was not significantly different than that of patients with wild-type PIK3CA (or PIK3CA/AKT1), while patients with two or three variants in PIK3CA (or PIK3CA/AKT1) exhibited poorer outcomes in the entire group and in all three subgroups (ER+, HER2‒, Ki67 high), particularly with respect to overall survival.ConclusionA high frequency of somatic PIK3CA mutations was detected in Chinese breast cancer patients. In addition to the mutation frequency, the tumor mutational burden of the PIK3CA and AKT1 genes should also be of concern, as they may be associated with poor prognosis.