Ki-67 Proliferation Index Values Research Articles

Prognostic value of KI-67 proliferation index in luminal breast cancers

Prognostic value of KI-67 proliferation index in luminal breast cancers

Apparent diffusion coefficient values effectively predict cell proliferation and determine oligodendroglioma grade

This study aims to evaluate the value of conventional magnetic resonance imaging (MRI) features and apparent diffusion coefficient (ADC) values in differentiating oligodendroglioma of various grades and explore the correlation between ADC and Ki-67. The preoperative MRI data of 99 patients with World Health Organization (WHO) grades 2 (n = 42) and 3 (n = 57) oligodendroglioma confirmed by surgery and pathology were retrospectively analyzed. Conventional MRI features, ADCmean, ADCmin, and normalized ADC (nADC) were compared between the two groups. A receiver operating characteristic curve was used to evaluate each parameter's diagnostic efficacy in differentiating the two tumor types. Each tumor's Ki-67 proliferation index was also measured to explore its relationship with the ADC value. Compared with WHO2 grade tumors, WHO3 grade tumors had a larger maximum diameter and more significant cystic degeneration/necrosis, edema, and moderate/severe enhancement (all P < 0.05). The ADCmin, ADCmean, and nADC values of the WHO3 and WHO2 grade tumors were significantly different, and the ADCmin value most accurately distinguished the two tumor types, yielding an area under the curve value of 0.980. When 0.96 × 10-3 mm2/s was used as the differential diagnosis threshold, the sensitivity, specificity, and accuracy of the two groups were 100%, 93.00%, and 96.96%, respectively. The ADCmin (r = -0.596), ADCmean (r = - 0.590), nADC (r = - 0.577), and Ki-67 proliferation index values had significantly negative correlations (all P < 0.05). Conventional MRI features and ADC values are beneficial in the noninvasive prediction of the WHO grade and tumor proliferation rate of oligodendroglioma.

Correlation Between Apparent Diffusion Coefficient and the Ki-67 Proliferation Index in Grading Pediatric Glioma.

This study aimed to investigate the correlation between apparent diffusion coefficient (ADC) and the Ki-67 proliferation index with the pathologic grades of pediatric glioma and to compare their diagnostic performance in differentiating grades of pediatric glioma. Magnetic resonance imaging examinations and histopathologies of 121 surgically treated pediatric gliomas (87 low-grade gliomas [LGGs; grades 1 and 2] and 34 high-grade gliomas [HGGs; grades 3 and 4]) were retrospectively reviewed. The mean tumor ADC (ADCmean), minimum tumor ADC (ADCmin), tumor/normal brain ADC ratio (ADC ratio), and value of the Ki-67 proliferation index of LGGs and HGGs were compared. Correlation coefficients were calculated for ADC parameters and Ki-67 values. The receiver operating characteristic curve was used to determine the diagnostic value of ADCmean, ADCmin, ADC ratio, and Ki-67 proliferation index for differentiating LGGs and HGGs. The ADC values were significantly negatively correlated with glioma grade, and the Ki-67 proliferation index had a significant positive correlation with glioma grade. A significant negative correlation was observed between ADCmean and Ki-67 proliferation index, between ADCmin and Ki-67 proliferation index, and between ADC ratio and Ki-67 proliferation index. The receiver operating characteristic analysis demonstrated moderate to good accuracy for ADCmean in discriminating LGGs from HGGs (area under the curve [AUC], 0.875; sensitivity, 79.3%; specificity, 82.4%; accuracy, 80.2%; positive predictive value [PPV], 92.0%; and negative predictive value [NPV], 60.9% [cutoff value, 1.187] [×10-3 mm2/s]). Minimum tumor ADC showed very good to excellent accuracy with AUC of 0.946, sensitivity of 86.2%, specificity of 94.1%, accuracy of 88.4%, PPV of 97.4%, and NPV of 72.7% (cutoff value, 0.970) (×10-3 mm2/s). The ADC ratio showed moderate to good accuracy with AUC of 0.854, sensitivity of 72.4%, specificity of 88.2%, accuracy of 76.9%, PPV of 94.0%, and NPV of 55.6% (cutoff value, 1.426). For the parameter of the Ki-67 proliferation index, in discriminating LGGs from HGGs, very good to excellent diagnostic accuracy was observed (AUC, 0.962; sensitivity, 94.1%; specificity, 89.7%; accuracy, 90.9%; PPV, 97.5%; and NPV, 78.0% [cutoff value, 7]). Apparent diffusion coefficient parameters and the Ki-67 proliferation index were significantly correlated with histological grade in pediatric gliomas. Apparent diffusion coefficient was closely correlated with the proliferative potential of pediatric gliomas. In addition, ADCmin showed superior performance compared with ADCmean and ADC ratio in differentiating pediatric glioma grade, with a close diagnostic efficacy to the Ki-67 proliferation index.

Prognostic value of KI-67 proliferation index in luminal breast cancers.

This study aimed to examine the prognostic significance of the KI-67 proliferation index, especially in breast cancer (BC) patients without HER-2 expression and no nodal involvement. The database of hormone-receptor-positive patients who underwent surgery for BC in our Surgical Oncology Clinic between 2008 and 2020 was retrospectively reviewed and recorded. Patients were categorized based on their KI-67 level, considering the cutoff value of 20%. Our study revealed that tumors with high KI-67 levels were more likely to have a more advanced histological grade (p = 0.00) and size (p = 0.038). In the univariant analysis, KI-67 level was effective on overall survival (p = 0.044) and disease-free survival (p = 0.048). However, we found that there was no independent prognostic factor in the multivariant analysis. Although the Ki-67 proliferation index does not yet have an agreed threshold value and scoring methodology, it can also be used to determine prognosis and evaluate treatment response in some patients.

Minimal apparent diffusion coefficient in predicting the Ki-67 proliferation index of pancreatic neuroendocrine tumors.

To investigate the diagnostic performance of the minimal apparent diffusion coefficient (ADCmin) to distinguish between pancreatic neuroendocrine tumors (Pan-NETs) with low and high Ki-67 proliferation index values and to evaluate the relationship between ADCmin and the Ki-67 proliferation index. Pre-operative magnetic resonance imaging data and postoperative Ki-67 proliferation index data of 42 patients with primary neuroendocrine tumor of the pancreas from November 2014 to March 2021 were included in this retrospective study. According to the Ki-67 proliferation index value, Pan-NETs were divided into a high-expression group (Ki-67 ≥ 10%, n = 17) and low-expression group (Ki-67 < 10%, n = 25), and mean ADC (ADCmean) and ADCmin values were compared between groups using receiver operating characteristic (ROC) curves to evaluate the performance of ADCmean and ADCmin in judging the expression level of Ki-67 proliferation index. The relationship between ADCmin and the Ki-67 proliferation index was also evaluated. The ADCmin was significantly higher in the low-expression group (Z = - 3.537, p < 0.01). The area under the ROC curve (AUC) for ADCmin was 0.825, which was higher than that for ADCmean (0.781). Using 1.32 × 10-3 mm2/s as the optimal discriminating threshold, the sensitivity, specificity, accuracy, and positive and negative predictive values of the two groups were 80%, 88.2%, 83.3%, 90%, and 75%, respectively. The ADCmin of Pan-NETs showed a significant negative correlation with the Ki-67 proliferation index (rs = - 0.634, p < 0.001). The ADCmin is a potential imaging biomarker, which may be helpful for non-invasive preoperative prediction of the Ki-67 proliferation index of Pan-NETs and the subsequent planning of appropriatetreatment.

Prognostic utility of Ki-67 in gastric carcinoma

Introduction: Gastric carcinoma represents the third leading cause of cancer related mortality worldwide. Most of cases are diagnosed at the time of tumor metastasis. There is a discrepancy in the results regarding the role of Ki-67 proliferation index as a prognostic factor in gastric carcinoma. Objectives: To assess the prognostic value of Ki-67 proliferation index and correlate Ki-67 expression with the overall survival (OS) in patients with gastric carcinoma. Patients and Methods: This retrospective study included fifty cases collected randomly from archival paraffin blocks of gastric carcinoma. Cases were collected during the period from 2013 to 2018. Sections were prepared and the slides were immunohistochemically stained with Ki-67 antibody. Results: This study showed a statistically significant correlation between higher percentage of Ki-67 expression and cases with tumors located in the fundus and body of the stomach and with distant metastasis. Also a statistically significant correlation between higher mean of Ki-67 positive cell % and cases of adenocarcinoma with pT1 tumors and with loco-regional recurrence (P &lt; 0.001, P=0.02). A higher percentage of Ki-67 expression was found in cases of adenocarcinoma grade III and cases with positive perineural invasion compared to other cases, yet the correlation was statistically insignificant. According to survival analysis, OS rate was 34.0% and the median OS time was 14.6 months. There was no statistically significant association between Ki-67 proliferation index and disease free survival (DFS) and OS. Conclusion: Ki-67 proliferation index can be used as a predictor for distant metastasis and loco-regional recurrence of gastric cancer.

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.

Diagnostic and Interventional Role of Endoscopic Ultrasonography for the Management of Pancreatic Neuroendocrine Neoplasms.

Pancreatic neuroendocrine neoplasms (PanNENs) are relatively rare, but their incidence has increased significantly in the last decades. Precise diagnosis and prognostic stratification are crucial for proper patient management. Endoscopic ultrasound (EUS) is the modality of choice for diagnosis of solid pancreatic tumors, showing a higher tumor detection rate than other imaging modalities, especially for small size lesions. EUS also serves as a guide for preoperative sampling and other interventions. EUS-tissue acquisition is a safe and highly accurate technique for cyto/histological diagnosis of PanNENs with a well-demonstrated correlation between Ki-67 proliferation index values and tumor grading on EUS and surgical specimens according to the WHO 2017 classification. Furthermore, the possibility of a preoperative EUS-guided fine needle tattooing or fiducial markers placement may help the surgeon to locate small and deep tumors, thus avoiding formal pancreatic resections in favor of parenchymal-sparing surgery. Finally, locoregional ablative treatments using either ethanol injection or radiofrequency ablation have been proposed in recent studies with promising results in order to control symptoms or reduce tumor burden in selected patients unfit for surgery with functioning or non-functioning PanNENs. This article review highlights the current role of EUS in PanNENs management, focusing on the present and future applications of EUS-guided interventions.

Ki-67 Proliferasyon İndeksi ve p53 Gen Ekspresyonunun Hipofiz Makroadenomalarının Hormon Profilleri, İnvazyon Dereceleri ve Operasyon Öncesi ve Sonrası Değerlendirilmesindeki Klinik Önemi

Objective: The aim of this study was to investigate the clinical significance of Ki-67 proliferation index and p53 gene expression in the pre-operative and post-operative evaluation of pituitary macroadenomas. Material and Methods: We retrospectively evaluated 81 pituitary macroadenoma patients, where pre-operative, six-month and one-year follow-up post-operative dynamic contrastenhanced magnetic resonance imaging examinations were present in our picture archiving and data system. All patients underwent surgical tumor removal and were pathologically diagnosed as having macroadenomas. Results: In Ki-67 positive macroadenoma cases, maximal tumor diameter was found significantly higher than in Ki-67 negative adenoma cases. When tumor invasiveness was compared based on Hardy's classification with the Ki-67 proliferation index values of macroadenomas, no statistically significant correlation was found between tumor invasiveness and Ki-67 values. We can state that there is a strong correlation between Ki-67 positiveness and increase in residual tumor dimensions. In p53 negative and positive macroadenoma cases, there was no significant correlation between p53 gene expression and maximal tumor diameter. When we compared the tumor invasiveness was compared based on Hardy's classification with the p53 gene expression of macroadenomas, no statistically significant correlation was found between tumor invasiveness and p53 values. We can say that there is a strong correlation between p53 gene expression positiveness and increase in residual tumor dimensions. Conclusion: Ki-67 proliferation index and p53 gene expression level determination of macroadenomas and their association with the hormone profiles, invasiveness, preoperative primary tumor and post-operative residual tumor dimension parameters can be combined in order to predict early tumor progression and patient prognosis.

Diagnostic role of apparent diffusion coefficient combined with intratumoral susceptibility signals in differentiating high-grade gliomas from brain metastases.

The aim of this study was to assess whether tumoral and peritumoral apparent diffusion coefficient values and intratumoral susceptibility signals on susceptibility-weighted imaging could distinguish between high-grade gliomas and brain metastases, and to investigate their associations with the Ki-67 proliferation index. Fifty-seven patients with pathologically confirmed diagnoses of either high-grade glioma or brain metastasis were enrolled in this study (23 with high-grade gliomas and 34 with brain metastases). The minimum and mean apparent diffusion coefficients in the enhancing tumoral region (ADCmin and ADCmean) and the minimum apparent diffusion coefficient in the peritumoral region (ADCedema) were measured from apparent diffusion coefficient maps, and intratumoral susceptibility signal grades acquired by susceptibility-weighted imaging were calculated. Ki-67 proliferation index values were obtained from the hospital database. These parameters were evaluated using the Mann-Whitney U test, independent-sample t-test, Spearman correlation analysis, receiver operating characteristic curve, and logistic regression analyses. ADCmean, ADCmin values, and intratumoral susceptibility signal grades in brain metastases were significantly lower than those in high-grade gliomas (all p < 0.05). Ki-67 proliferation index values showed significant correlations with ADCmean, ADCmin, and intratumoral susceptibility signal grade in brain metastases (all p < 0.05), but no correlation was found in high-grade gliomas (all p > 0.05). According to receiver operating characteristic curve analysis, ADCmean achieved the highest diagnostic performance for discriminating high-grade gliomas from brain metastases. Furthermore, the combination of tumoral apparent diffusion coefficient parameters with intratumoral susceptibility signal grade provided a higher area under the curve than univariate parameters. The combination of tumoral apparent diffusion coefficient with intratumoral susceptibility signal grade can offer better diagnostic performances for differential diagnosis. Apparent diffusion coefficient and intratumoral susceptibility signal may reflect cellular proliferative activity in brain metastases, but not in high-grade gliomas.

Correlation of folate receptor alpha expression with clinicopathological parameters and outcome in triple negative breast cancer

Folate receptor alpha (FRα) is a membrane-bound protein with a high affinity for folate, which is necessary for the biosynthesis of amino acids and nucleotide bases. It has been shown to be a potential prognostic and therapeutic target, primarily in lung and ovarian cancer, as well as in breast cancer. The aim of this study was to examine FRα expression in a cohort of patients with triple negative breast cancer (TNBC), in correlation with clinicopathological parameters and prognostic factors. By using polyclonal FRα antibody on archival paraffin blocks immunohistochemistry was performed. To evaluate the expression of FRα, H-score was used, which marks both the proportion of stained cells and the intensity of staining. Statistical analysis correlating FRα expression with clinicopathologic parameters and clinical outcome were performed. FRα was expressed in most of the patients (85%). Significant correlation of expression and histologic grade (Mann Whitney U test, P = 0,03) and type of tumor (P = 0,02), was found. It was noticed that with higher Ki-67 proliferation index values, H-score has lower values (r = −0,284, P = 0,006). Multivariant regression analysis (Cox regression, Stepwise method) showed H-score as a significant predictor for the risk of disease recurrence (OR = 1,005, P = 0,04). No correlation between FRα expression and overall survival (OS) and disease-free survival (DFS) was found.In conclusion, FRα is highly expressed in TNBC, and, given the correlation with clinicopathological parameters, subpopulation of patients could be identified that could be potential targets for new therapeutic perspectives in the treatment of this breast cancer subtype.

Prognostic relevance of the Ki-67 proliferation index in patients with mantle cell lymphoma.

BackgroundA high Ki-67 proliferation index (PI) in neoplastic cells is associated with poor survival in mantle cell lymphoma (MCL). We aimed to determine the cut-off values for the Ki-67 PI as a prognostic factor in MCL according to bone marrow findings.MethodsImmunohistochemical (IHC) staining for Ki-67 was performed on formalin-fixed paraffin-embedded biopsy tissues from 56 patients with MCL. Patients were grouped based on their Ki-67 PI values. Survival analyses were carried out and the cut-off value for the Ki-67 PI was determined.ResultsOf the 56 patients, 39 (69.6%) showed bone marrow involvement of MCL; 21 of these patients had leukemic manifestations at the time of diagnosis. The results of the Ki-67 IHC staining were as follows: ≤10% in 22 patients, 11–20% in 14 patients, 21–30% in 3 patients, 31–40% in 4 patients, 41–50% in 4 patients, and >50% in 9 patients. A cut-off value of 20% revealed significantly different survival rates with mean survival times of 69.8 months (Ki-67 PI≤20%) and 47.9 months (Ki-67 PI>20%), irrespective of bone marrow findings (P=0.034). Clinical outcomes did not differ, regardless of bone marrow findings. However, in cases with bone marrow involvement, the Ki-67 cut-off value of 30% for overall survival was required to yield statistical significance (P=0.033).ConclusionThe 20% cut-off value for the Ki-67 PI was clinically meaningful, regardless of bone marrow involvement of MCL. For patients with bone marrow involvement, the statistically significant cut-off value increased to 30%.

Relation of apparent diffusion coefficient with Ki-67 proliferation index in meningiomas.

The purpose of this study was to investigate the relationship between Ki-67 proliferation indexes and apparent diffusion coefficient (ADC) values of low-grade and atypical/anaplastic (high-grade) meningiomas. Pre-operative diffusion-weighted imaging and histopathological evaluation of 44 patients with meningiomas were performed retrospectively. Regions of interest (ROIs) were manually drawn on the ADC images. In total six ROI measurements were taken in three consecutive slices, and the average of the mean ADC value was used. The relationship between the ADC and Ki-67 values was investigated, and the ADC values of the low-grade and high-grade meningiomas were compared. 31 (70%) patients had low-grade the meningiomas. 10 (23%) patients had atypical and 3 (7%) had anaplastic meningiomas. ADC values of the low-grade and high-grade meningiomas were 0.81 ± 0.12 × 10(-3) and 0.66 ± 0.08 × 10(-3) mm(2) s(-1), respectively. Ki-67 proliferation indexes were 2.19% ± 1.14% for low-grade and 11.20% ± 9.80% for high-grade meningiomas. A statistically significant negative correlation between Ki-67 proliferation index and ADC values of the low-grade and high-grade meningiomas was detected (r(2) = 0.326, p < 0.001). High-grade meningiomas had lower ADC values than that of low-grade meningiomas. There was statistically significant difference between the ADC values of the low-grade and high-grade meningiomas (p < 0.001). Our data provide an inverse correlation between the ADC and Ki-67 proliferation index values of meningiomas. ADC values can be used for histopathological characterization of the meningiomas and pre-surgical planning. The purpose of this study was to investigate the relationship between Ki-67 proliferation indexes and ADC values of low-grade and atypical/anaplastic (high-grade) meningiomas. In addition, we compared the ADC and Ki-67 proliferative index values of the low-grade and atypical/anaplastic (high-grade) meningiomas. We concluded that there was an inverse correlation between the ADC and Ki-67 proliferation index values in meningiomas, and we have found statistically significant difference between the ADC values of the low-grade and high-grade meningiomas. ADC values can be used for histopathological characterization of the meningiomas and pre-surgical planning.

The influence of Ki-67 proliferation index on Tc-99m-EDDA-HYNIC-TOC somatostatin receptor scintigraphy in patients with carcinoids

Abstract The aim of this paper is to determine the influence of Ki-67 proliferation index on somatostatin receptor scintigraphy (SSRS) with Tc-99m-EDDA-HYNIC-TOC (Tc-99m-Tektrotyd) somatostatin analogue in patients with carcinoid tumors. Sixty-one patients (31 female, 30 male; age range: 33-76 years) were examined: 13 patients highly suspected of having a carcinoid, and 48 patients who had undergone the surgical removal of the tumor. Whole body SSRS at 4 h postinjection, spot scintigrams and SPECT of the selected regions were obtained for all patients. Tc-99m-Tektrotyd scintigraphy was classified as true positive in 26 out of 30 and true negative in 24 out of 28 patients. The sensitivity of Tc-99mTc-Tektrotyd scintigraphy was found to be as high as 94.74% in the group of patients with low mitotic index Ki67 (&lt;2%), and it progressively decreased in patients with higher mitotic index (77.78% for Ki67 2-15% and 20% for Ki67% &gt;20%). The likelihood of Tc-99m-Tektrotyd scan being positive when a carcinoid is present was found to be inversely proportional to the value of Ki67 proliferation index. The results showed that Tc-99m-Tektrotyd SSRS is a sensitive method for diagnosing and staging patients with well-differentiated carcinoid tumors. However, in poorly differentiated tumors with high Ki67 proliferation index, additional analyses are necessary for precise staging.

Correlation of apparent diffusion coefficient with Ki-67 proliferation index in grading meningioma.

A noninvasive method to predict aggressiveness of high-grade meningiomas would be desirable because it would help anticipate tumor recurrence and improve tumor management and the treatment outcomes. The Ki-67 protein is a marker of tumor proliferation, and apparent diffusion coefficient (ADC) is related to tumor cellularity. Therefore, we sought to determine whether there is a statistically significant correlation between ADC and Ki-67 values in meningiomas and whether ADC values can differentiate various meningioma subtypes. MRI examinations and histopathology of 68 surgically treated meningiomas were retrospectively reviewed. Mean ADC values were derived from diffusion imaging. Correlation coefficients were calculated for mean ADC and Ki-67 proliferation index values using linear regression. An independent unpaired Student t test was used to compare the ADC and Ki-67 proliferation index values from low-grade and more aggressive meningiomas. A statistically significant inverse correlation was found between ADC and Ki-67 proliferation index for low-grade and aggressive meningiomas (r(2) = -0.33, p = 0.0039). ADC values (± SD) of low-grade meningiomas (0.84 ± 0.14 × 10(-3) mm(2)/s) and aggressive (atypical or anaplastic) meningiomas (0.75 ± 0.03 × 10(-3) mm(2)/s) were significantly different (p = 0.0495). Using an ADC cutoff value of 0.70 × 10(-3) mm(2)/s, the sensitivity for diagnosing aggressive meningiomas was 29%, specificity was 94%, positive predictive value was 67%, and negative predictive value was 75%. ADC values correlate inversely with Ki-67 proliferation index and help differentiate low-grade from aggressive meningiomas.