Ki-67 In Breast Carcinoma Research Articles

Expression of p53 and ki-67 in Breast Carcinomas and Their Association with Histopathological Type, Grade, and Stage

Background & objective: Recently many laboratories are evaluating the usefulness of determining p53, and Ki67 proliferation activities using immunohistochemical techniques in cancer. Although the available studies suggest that these factors might help make treatment decisions in cancer patients, their clinical usefulness is still controversial. The present study was undertaken to see the expression of p53 and Ki-67 in breast carcinoma and their associations with histopathological variables. Methods: This cross-sectional analytical study was conducted in the Department of Pathology, in collaboration with the Department of Surgery, Rajshahi Medical College Hospital and the Department of Pathology, Bangobandhu Sheikh Mujib Medical University (BSMMU), Dhaka over a period of one and a half year from July 2018 to December 2019. Resected specimens of breast tissue, histopathologically confirmed as breast carcinoma, were the study population. Histological grading of breast carcinoma was done according to Nottingham modification of the Bloom-Richardson system, while staging was done using Tumor-Node-Metastasis (TNM) classification of malignant tumors, as recommended by the Union for International Cancer Control (UICC). The Ki67 and p53 expressions were assessed by immunohistochemistry. Based on the Ki67 labeling index (Ki67-LI), the patients were divided into two groups – Ki 67 > 30% (considered as over-expressed) and ≤ 30% (considered as less expressed). Likewise, p53 immuno-expression was grouped as over-expressed (score ≤ 8) and low-expressed (score > 8). The histological grade, type, and stage were then compared between patients with tumours of high and low proliferating activities to find the associations of Ki67 and p53 with tumor grade, type, and stage. Result: In the present study, almost three-quarters (74%) of the specimen of the breast had high Ki67-LI and 26% intermediate and low Ki67-LI. The p53 was found to be highly expressed in the majority (86%) of the cases. Analyses of the association of biomarkers with histological grade, stage, and type revealed that advanced-stage breast cancers (Stage-IIIA) were more likely to be associated with high Ki67-LI than the early-stage breast cancers (Stage-IIA and Stage-IIB) (p = 0.023). Poorly differentiated (G3) carcinoma also more often tends to be associated with high Ki67-LI than with low and intermediate Ki67-LI (p = 0.066). Likewise, stage IIIA tumors and poorly differentiated carcinoma were also considerably higher in the p53 over-expressed group (23.3%) than in the low p53 expression group (14.3%) (p = 0.023). Conclusion: The study concluded that a substantial proportion of breast carcinomas demonstrates high Ki67-LI. The p53 overexpression is also found in the majority (86%) of the breast carcinoma cases. Both Ki67 and p53 proliferation activities show their significant presence in high-grade and advanced-stage tumours. Ibrahim Card Med J 2023; 13 (1&2): 11-18

TRIPLE MARKERS (ER, PR, HER 2 NEU) AND THEIR RELATIONSHIP WITH KI67 EXPRESSION IN BREAST CARCINOMA - AN OBSERVATIONAL STUDYIN NORTH EAST INDIA

Background:Breast cancer is the most common and deadly malignancy of women globally. Breast cancer is called ER/PR positive if it has receptors for hormone estrogen/progesterone. Similarly HER2neu positive status of breast carcinoma means that HER2neu gene is making too many HER2neu proteins. Hormone receptor studies with ER, PR & HER2neu are routinely done in breast carcinoma. Ki67 is an independent factor to predict tumour grade. Breast carcinoma can therefore be classified based on expression patterns of ER, PR, HER2neu & correlated with Ki67 into various molecular subtypes. Objectives:(1) To determine the association between expression patterns of ER, PR and HER2neu with Ki67 in breast carcinoma in patients attending our hospital. (2) To estimate the proportion of different molecular subtypes of breast carcinoma. Materials & Methods: It was an observational cross sectional study done on 122 cases for a period of 2 years(July 2020- June 2022) and surgical specimens from patients operated for breast carcinoma of all ages along with true cut biopsies were included. Immunohistochemical study for ER, PR, HER2Neu & Ki67 were performed on breast tissue specimens received. Results:The study found inverse correlation of Ki67 with ER, PR and its direct correlation with Her2Neu. TNBC (Triple Negative Breast Carcinoma) was the most predominant molecular subtype. Conclusion:High Ki67 is considered as an unfavourable factor influencing tumour progression and is associated with poor prognosis. Ki67 is a potential prognostic biomarker in breast cancers and such prognostic information could be beneficial for development of therapeutic strategy.

A study on the role of proliferative index marker Ki67 in breast carcinoma

Background. Breast cancer is the most common malignancy and the leading cause of cancer death among women worldwide. This study was conducted to establish early diagnosis and therapy, thus improving prognosis and overall survival rate. Objectives. To assess the levels of proliferation index marker Ki67 and hormone receptor status in patients with breast carcinoma and to correlate Ki67 with ER, PR, Her2neu status, as well as to correlate Ki67 and hormone receptor status with onco-pathological parameters. Materials and Methods. 392 patients diagnosed with breast carcinoma over a period of four years were included in the study. Data regarding patient’s identification, history, clinical finding, investigations and histopathological report were recorded in a specific proforma. Result. Breast cancer was seen to affect people in the older age group, and invasive ductal carcinoma of nonspecific type was the most common type. Most patients had unifocal tumor with grade 2 disease. Stage II disease was most common stage among the patients studied and Luminal B subtype was the predominant type of molecular subtype. Most of the patients were Ki67 positive, i.e., Ki67 >14%. The correlation of Ki67 with estrogen receptor, progesterone receptor, tumor size, mitotic count, lymph node ratio, lymphovascular invasion and extra-nodal extension was found to be statistically significant. Conclusions. There exists a statistically significant, positive correlation between breast cancers, its onco-pathological parameters, proliferation index marker Ki67 and hormone receptor status. Therefore, the judicious use of these tests (Ki67 is an old marker of proliferation but not routinely used) will help in the early appropriate treatment of patients and contribute to the assessment of treatment response and prognosis.

A study on Nottingham prognostic index and its correlation with ER, PR, HER-2/NEU AND KI-67 in breast carcinomas

Aim: Carcinoma of the breast is one of the most common malignancy in women. Considering the tumour size, histological grade and number of lymph nodes involved, Nottingham Prognostic index (NPI) is calculated. This study has been designed to acquire information about various parameters in breast carcinomas and to calculate NPI score in each case and determine the relationship of NPI with various prognostic markers in breast carcinomas. Materials and Methods: The present study was undertaken in the Department of Pathology, Father Muller Medical College, Mangalore for a period of two years. Breast cancers, diagnosed as Invasive carcinoma breast of no special type on lumpectomy and mastectomy was studied and cases were assessed with regard to age, laterality, quadrant involved, size of the tumour, lymph node status, modified SBR grade, hormonal receptor status (ER, PR), HER-2/Neu, Ki-67 and NPI status of the tumour. Statistics: Cross tabulation was done to check for correlation and Kappa statistics was done to check the level of agreement between NPI and modified SBR grade, ER, PR, HER-2/Neu and Ki-67. Results and Conclusion: This study included a total of 100 infiltrating ductal carcinomas of the breast. The mean age of presentation was 52.05 years. On cross tabulation of NPI with pathological parameters only modified SBR grade showed statistically significant association with NPI at 5% level of significance(‘p’ Keywords: Breast neoplasms, Carcinoma, Ductal, NPI.

An Advanced Automated Image Analysis Model for Scoring of ER, PR, HER-2 and Ki-67 in Breast Carcinoma

Immunohistochemistry (IHC) plays an important role in evaluating the status of ER, PR, Ki-67 and human epidermal growth factor receptor 2 (HER-2) during diagnosis of breast cancer. Although some existing automated approaches can solve the high time-consumption and inter-/intra-observer variability drawbacks to a certain extent, most of them are can’t analyze both nuclear staining and cell membrane staining using the same method. This is attributed to the difference in localization of the positive signal of immunohistochemical staining in different biological markers. The present study proposes a novel automated image analysis model for scoring and grading of ER, PR, Ki-67 and HER-2 immunohistochemical images based on whole tissue sections in breast cancer. The scoring results of the trained model and manual interpretation of ER, PR, Ki-67 and HER-2 were then finally analyzed and compared. Experimental results show that the F1-measure was 0.8450, 0.8533 and 0.7962 for nuclear recognition of Ki-67, ER/PR and HER-2 respectively. For stain grading of Ki-67, ER/PR and HER-2, the F1-measure was 0.9776, 0.8306 and 0.9573 respectively. The scoring consistency of ER/PR, Ki-67 and HER-2 between our model and expert interpretation was 0.9279, 0.9712 and 0.8046 respectively. Our results demonstrate that artificial intelligence technology is a feasible and accurate method for accurate quantitative immunohistochemical analysis that can solve the drawbacks of low repeatability and time consumption brought by manual counting. The main contribution of our proposed model is that it can recognize both nuclear staining and cell membrane staining and grade the staining intensity as a sequential learning task.

Role of Ki67 in breast carcinoma and its association with clinicopathological parameters and luminal subtypes in a tertiary health care center

Introduction & Objectives: In clinical practice, the evaluation of the breast tumour proliferative fraction is of important for the treatment decision, which is commonly performed by the immunohistochemical staining of a proliferation marker, the Ki67 antigen. The main objective of the current study was to analyze and evaluate the associations between Ki-67 and common histopathological parameters and luminal subtypes in the routine clinical setting. Materials and Methods: A total of seventy cases were enrolled in the study. The surgical specimens were evaluated and histopathological reporting was done according to College of American Pathologists (CAP) guidelines. Suitable blocks were selected and immunostaining was performed with ER, PR, Her2/neu and Ki67 markers. The association between the Ki-67 and histopathological parameters [age, histological type, nuclear grade, tumor size, multifocality, an in situ component, lymphovascular invasion (LVI), estrogen and progesterone receptor (ER/PR) expression, human epidermal growth factor receptor (HER-2) status, axillary involvement and tumor stage] were evaluated in each group. The data thus obtained was analyzed by SPSS-20 software with chi square test. Results: The intended age of presentation in the current study was 48.6613.05 years and most common histological type was invasive ductal carcinoma of no special type (IDC-NST). Tumor size was found to have an association with Ki67 expression status with significant p value (0.003), were as tumor grade and pT category did not find any significant association with Ki67 expression. Luminal subtypes and ki67 expression status was seen to have an association with significant p value. Conclusion: Ki67 was considered as important marker to predict the prognosis for better management of breast cancer patients. Keywords: Histopathological parameters, immunohistochemistry, proliferation marker.

CD10 expression by stromal cells in carcinoma of breast and its correlation with ER, PR, HER2neu and Ki67-A tissue microarray study in a tertiary care hospital

Introduction: CD10 is a metalloproteinase (Zinc dependent) which is expressed in stroma of various epithelial malignancies. It is associated with biological aggressiveness of the tumor. Till now very few studies has been undertaken correlating CD10 with other prognostic markers like lymphnode status, tumor grade, stage, ER, PR, HER2-neu and ki67 in breast carcinoma. Aim: To see the CD10 expression in breast carcinoma and correlate it with ER, PR, HER2 neu and ki67. Materials and Methods: 55 cases of carcinoma breast were diagnosed on histology. Tissue microarray blocks were prepared and Immunohistochemistry was performed for ER, PR, HER2neu, Ki67 and CD10. Result: 32(58%) cases are CD10 positive and 23 (42%) cases are CD10 negative. Out of this 32 positive cases, 12 (22%) cases are weak positive and 20 (36%) cases are strong positive. CD10 is positively correlated with tumor grade.CD10 is negatively correlated with ER and PR status which is not statistically significant and no correlation is found between CD10 and HER2-neu. A positive correlation is seen between CD10 and ki67, but it is not statistically significant. Conclusion: CD10 expression is positively correlated with Ki67 and increasing tumor grade and whereas inversely correlated with ER and PR status. No correlation is seen between CD10 with lymph node status and HER2-neu. Keywords: Breast carcinoma, Histomorphology, IHC, Tissue microarray.

The Correlation between Traditional Ultrasound Features and the Expression of Estrogen Receptor, Progesterone Receptor, Human Epidermal Growth Factor Receptor-2, and Ki-67 in Breast Carcinoma

The Correlation between Traditional Ultrasound Features and the Expression of Estrogen Receptor, Progesterone Receptor, Human Epidermal Growth Factor Receptor-2, and Ki-67 in Breast Carcinoma

The Reliability of Core-Needle Biopsy in Assessment of Hormone Receptor, HER2, and Ki-67 in Breast Carcinoma

Objective: The purpose of this study was to compare the estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) status and Ki-67 index by immunohistochemical (IHC) analysis in breast carcinoma to determine the level of concordance between core-needle biopsy (CNB) and surgical specimens. Summary of Background: Accurate preoperative diagnosis of a breast lesion has recently been considered essential to the treatment strategy to achieve optimal treatment without delay. However, the reliability of using CNB specimens for IHC assessment is in relatively small number of cases and differing results between previous studies. Methods: The patients included in this study were 255 patients with primary breast carcinoma who had CNB and subsequent surgical resection at the Hospital of Dokkyo Medical University between 2010 and 2016. We compare the ER, PgR, HER2 status, and Ki-67 index by IHC analysis in breast carcinoma between CNB and surgical specimens. Results: There was a concordance rate between the ER, PgR, HER2, and Ki-67 IHC assessment of CNB and surgical specimens in 99.0%, 92.1%, 86.3%, and 91.5%, respectively. We also found small numbers of discordant cases in the estimation for which a discrepancy in determination led to a change in treatment. Conclusions: Our results do not entirely invalidate the use of CNB for assessment if they are the only source of tumor tissue available, but suggest a more cautious approach in their interpretation when clinical decisions are being made.

Abnormal expression of miR-1 in breast carcinoma as a potent prognostic factor.

Metastatic breast cancer remains a highly lethal disease, and it is very important to evaluate the biomarkers associated with the distant metastasis. MicroRNA (miRNA) are small non-protein coding RNA that regulate various cellular functions. Recent investigations have demonstrated the importance of some miRNA in breast cancer, but the significance of the great majority of miRNA remains largely unclear in breast cancer metastasis. Therefore, in this study, we first examined expression profiles of miRNA in stageIV breast carcinoma tissues, comparing stageI-III cases by miRNA PCR array, and identified miR-1 as the miRNA which was the most associated with the distant metastasis. However, miR-1 has not yet been examined in breast carcinoma tissue, and its significance remains unknown. Therefore, we further examined miR-1 expression in breast carcinoma using insitu hybridization (ISH). miR-1 was localized in carcinoma cells in 20% of breast carcinoma cases, but it was negligible in non-neoplastic mammary glands or stroma. miR-1 ISH status was significantly associated with stage, pathological T factor, lymph node metastasis, distant metastasis, histological grade, estrogen receptor, progesterone receptor and Ki-67 in breast carcinoma. Moreover, the miR-1 status was demonstrated using multivariate analysis as an independent worse prognostic factor for both disease-free and breast cancer-specific survival. These findings suggest that abnormal miR-1 expression is associated with an aggressive phenotype of breast carcinoma and that miR-1 status is a potent prognostic factor in human breast cancer patients.

Hexokinase II is a prognostic factor associated with HIF‐1α and Ki‐67 in breast carcinoma. Immunohistochemistry for hexokinase II in the invasive edge of breast carcinoma.See also Sato‐Tadano, A., et al.

Cancer ScienceVolume 104, Issue 10 p. October cover-October cover Cover ImageOpen Access Hexokinase II is a prognostic factor associated with HIF-1α and Ki-67 in breast carcinoma. Immunohistochemistry for hexokinase II in the invasive edge of breast carcinoma.See also Sato-Tadano, A., et al. Akiko Sato-Tadano, Akiko Sato-TadanoSearch for more papers by this authorTakashi Suzuki, Takashi SuzukiSearch for more papers by this authorMasakazu Amari, Masakazu AmariSearch for more papers by this authorKiyoshi Takagi, Kiyoshi TakagiSearch for more papers by this authorYasuhiro Miki, Yasuhiro MikiSearch for more papers by this authorKentaro Tamaki, Kentaro TamakiSearch for more papers by this authorMika Watanabe, Mika WatanabeSearch for more papers by this authorTakanori Ishida, Takanori IshidaSearch for more papers by this authorHironobu Sasano, Hironobu SasanoSearch for more papers by this authorNoriaki Ohuchi, Noriaki OhuchiSearch for more papers by this author Akiko Sato-Tadano, Akiko Sato-TadanoSearch for more papers by this authorTakashi Suzuki, Takashi SuzukiSearch for more papers by this authorMasakazu Amari, Masakazu AmariSearch for more papers by this authorKiyoshi Takagi, Kiyoshi TakagiSearch for more papers by this authorYasuhiro Miki, Yasuhiro MikiSearch for more papers by this authorKentaro Tamaki, Kentaro TamakiSearch for more papers by this authorMika Watanabe, Mika WatanabeSearch for more papers by this authorTakanori Ishida, Takanori IshidaSearch for more papers by this authorHironobu Sasano, Hironobu SasanoSearch for more papers by this authorNoriaki Ohuchi, Noriaki OhuchiSearch for more papers by this author First published: 03 October 2013 https://doi.org/10.1111/cas.12242AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume104, Issue10October 2013Pages October cover-October cover RelatedInformation

Triple Negative Breast Carcinoma: A Comparative Study between Breast Lesion and Lymph Node Metastases: A Preliminary Study

Aims and Background. Triple negative breast carcinoma is a genetic and molecular subtype of breast carcinoma with poor prognosis. Some immunohistochemistry studies have been proposed to identify BLBC. Most studies consider primary breast carcinoma but not metastases.Methods. Immunohistochemical characteristics in 11 triple negative breast carcinomas were studied in both primary lesions and lymph node metastases. All cases were reevaluated to estrogen and progesterone receptors and HER2-Neu. An FISH probe for HER2/neu was also performed. Immunohistochemical studies were performed with cytokeratin 5/6, 17, Cam 5.2, p63, EGFR, and Ki-67 in breast carcinoma and lymph node metastases.Results. The age of the patients ranged between 42 and 73 years (mean 53), and the mean followup was 68.25 months. A total of 54.55% of the patients were disease-free, and 45.45% died of carcinoma. Axillary lymph nodes maintained triple negative phenotype (11/11). Metastatic tumors showed CAM 5.2 (81.83%) and EGFR (72.73%) expression. Basal marker expression was variable in primary carcinoma and lymph node metastases (63.64%).Conclusions. Triple negative breast carcinomas maintained this immunoprofile at lymph node metastases. Triple negative carcinomas showed variable expression of basal cell markers.

Prognostic Value of Estrogen Receptor and Ki-67 Index after Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer Expressing High Levels of Proliferation at Diagnosis

Purpose: Breast cancers expressing high levels of Ki-67, a nuclear marker of cell proliferation, are associated with worse outcome. Recent data from neoadjuvant studies indicate that a single measurement of the nuclear proliferation marker Ki-67 in breast carcinoma during neoadjuvant therapy is strongly predictive of long-term outcome. Secondly, recent literature data indicate that prognostic evaluation with Ki-67 may be better after pre-surgical therapy. A retrospective study from a prospectively maintained clinical database to compare the predictive and prognostic significance of biological markers, assessed before and after neoadjuvant chemotherapy, in locally advanced breast cancer, was performed. Patients and Methods: The following parameters were considered before and after chemotherapy for their relationship with treatment response and disease-free survival in 64 patients with locally advanced breast cancer: clinical stage, clinical and pathological lymph node involvement, Ki-67, estrogen receptor (ER), progesterone receptor (Pgr), Her2, tumor grade, clinical response, type of surgery performed, and number of chemotherapy cycles administered. The expression of Ki-67 was assessed using immunohistochemistry in pre-therapy tru-cut and post-therapy surgical excision specimens after neoadjuvant chemotherapy; only patients with breast tumors expressing high baseline Ki-67 (≧15%) were included in the analysis. In addition, the correlation between pre-chemotherapy biological markers and clinical and pathological response was reported. Results: Post-chemotherapy Ki-67 proliferation index decrease, pre-chemotherapy ER expression and post-chemotherapy ER expression were the only significant prognostic factors adversely influencing disease-free survival in univariate analysis. Her2 overexpression was the only factor to impact on the clinical response. Conclusions: Post-treatment Ki-67 and ER status were predictors of outcome for patients with locally advanced breast cancer and a high pre-chemotherapy proliferation index.

Expression of Ki-67 in breast carcinomas and its relationship with others prognostic variables

Expression of Ki-67 in breast carcinomas and its relationship with others prognostic variables