Clinicopathological Parameters Of Breast Cancer Research Articles

Clinico-pathological association of BCL2 in invasive breast carcinoma: A study from tertiary care health centre in Northern India.

B-cell lymphoma 2 (Bcl-2) is an antiapoptotic protein and an important clinical breast cancer prognostic marker. The aim of this study was to evaluate the relationship between the BCL2 expression and clinico-pathological parameters in breast cancer. Present study is observational cross-sectional study of 100 biopsy proven cases of breast cancer, and cases with resection specimens were included. IHC analyses for ER, PR, Her2neu, Ki67 and Bcl2 were performed in each case. Bcl2 expression was seen in 52% cases. BCL2-positive expression was associated with lower histological grade (0.026), low Ki-67 level (<14%, P < 0.001), hormone receptor positivity (P < 0.001) and luminal breast cancer (P < 0.001) but no association with tumour size, lymphovascular invasion, perineural invasion and TNM stage. Expression of Bcl-2, an antiapoptotic protein, is associated with low-grade, slowly proliferating, luminal A-type BC. IHC analysis of Bcl-2 is simple, inexpensive, readily available test to stratify early-stage hormone-positive patients who can be included in clinical trials for Bcl-2 inhibitors.

Immunohistochemical Expression of Cyclooxygenase 2 (COX-2) as a Prognostic Marker and Its Correlation With Clinicopathological Parameters in Breast Cancer.

Introduction Breast cancer is considered the most common cancer among women. According to the literature, cyclooxygenase-2 (COX-2) expression in breast carcinoma is associated with aggressive tumor biology and acts as an independent prognostic marker. As COX-2 is a newly identified marker, studies are required to understand its immunoexpression and correlation with hormone receptor status and other prognostic factors, which helps in the therapeutic management of patients. Hence, this study evaluates the expression of COX-2 in breast carcinoma. Methods A hospital-based cross-sectional study was done on 55 mastectomy specimens collected at the Histopathology and Surgical Pathology Section of the Department of Pathology. The patient's age, histological type, tumor size, lymph node status, histological grade, and vascular invasion were noted. Immunohistochemical staining for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2/neu protooncogene (HER2/neu), and COX-2 markers was performed, and its results were compared with these clinicopathological and prognostic parameters. Results were subjected to statistical analysis. Results COX-2 expression was seen in 37 out of 55 cases (67.2%). Expression of COX-2 showed a statistically significant correlation with vascular invasion, ER-negative status, and PR-negative status. No statistical association was found between other parameters like age, tumor size, histological type, histological grade, lymph node status, and HER2/neu status. Conclusion The expression of COX-2 correlated strongly with well-established poor prognostic markers, such as vascular invasion, ER-negative status, and PR-negative status. Thus, expression of COX-2 suggests aggressive tumor biology, and it can be used as an independent prognostic marker.

CLINICOPATHOLOGICAL STUDY OF BREAST CANCER AND IMMUNOHISTOCHEMICAL EXPRESSION OF BRCA 1 AND BRCA2 – A PROSPECTIVE STUDY

Objectives: The aim of this study was to study morphological features of breast cancer (BRCA), to grade according to Nottingham’s modification of Bloom Richardson (BR) grading system and to detect the immunohistochemical (IHC) expression of BRCA 1 and BRCA 2 proteins among the clinicopathological parameters of BRCA as age, menopausal status, tumor size, histopathological grade, and lymphnode status. Methods: This is a prospective and observational study conducted in the Department of Pathology from January 2015 to October 2016, Histopathological examination of 79 cases of Breast carcinoma was conducted and IHC using BRCA 1 and BRCA2 was done in 40 cases. Results: Out of 79 invasive breast carcinoma, the most common age group for breast carcinoma was 40–49 (40.5%) years. The most common histological subtype was invasive carcinoma-NST, 77(97.4%) cases. Forty cases studied for both BRCA-1 and BRCA 2 expression, regarding BRCA-1 expression, 11 cases showed score 1, 19 cases were of score 2, and eight cases belonged to score 3. Two cases did not show any expression. A positive statistical correlation existed between the size of the tumor, modified BR grade of tumor with BRCA-1 expression. Regarding BRCA-2 expression, 12 cases showed score 1, 17 cases was of score 2, and 10 cases belonged to score 3. One case did not show any expression. Conclusion: BRCA gene participates in the pathogenesis of breast carcinomas. It is an indicator of poor prognosis. BRCA positivity decreased with increase in age, size of tumor, lymphnodes showing metastasis, and higher grade of the tumor. The present study indicates that BRCA is a powerful predictor of prognosis.

Hyperglycemia induces PFKFB3 overexpression and promotes malignant phenotype of breast cancer through RAS/MAPK activation

BackgroundBreast cancer is the most common tumor in women worldwide. Diabetes mellitus is a global chronic metabolic disease with increasing incidence. Diabetes mellitus has been reported to positively regulate the development of many tumors. However, the specific mechanism of hyperglycemic environment regulating breast cancer remains unclear. PFKFB3 (6-phosphofructose-2-kinase/fructose-2, 6-bisphosphatase 3) is a key regulatory factor of the glycolysis process in diabetes mellitus, as well as a promoter of breast cancer. So, we want to explore the potential link between PFKFB3 and the poor prognosis of breast cancer patients with hyperglycemia in this study.MethodsCell culture was utilized to construct different-glucose breast cancer cell lines. Immunohistochemistry was adopted to analyze the protein level of PFKFB3 in benign breast tissues, invasive ductal carcinoma with diabetes and invasive ductal carcinoma without diabetes. The Kaplan–Meier plotter database and GEO database (GSE61304) was adopted to analyze the survival of breast cancer patients with different PFKFB3 expression. Western blot was adopted to analyze the protein level of PFKFB3, epithelial–mesenchymal transition (EMT)-related protein and extracellular regulated protein kinases (ERK) in breast cancer cells. Gene Set Cancer Analysis (GSCA) was utilized to investigate the potential downstream signaling pathways of PFKFB3. TargetScan and OncomiR were utilized to explore the potential mechanism of PFKFB3 overexpression by hyperglycemia. Transfections (including siRNAs and miRNA transfection premiers) was utilized to restrain or mimic the expression of the corresponding RNA. Cell functional assays (including cell counting, MTT, colony formation, wound-healing, and cell migration assays) were utilized to explore the proliferation and migration of breast cancer cells.ResultsIn this study, we demonstrated that the expression of PFKFB3 in breast cancer complicated with hyperglycemia was higher than that in breast cancer with euglycemia through cell experiment in vitro and histological experiment. PFKFB3 overexpression decreased the survival period of breast cancer patients and was correlated with a number of clinicopathological parameters of breast cancer complicated with diabetes. PFKFB3 promoted the proliferation and migration of breast cancer in a hyperglycemic environment and might be regulated by miR-26. In addition, PFKFB3 stimulated epithelial-mesenchymal transition of breast cancer in a hyperglycemic environment. In terms of downstream mechanism exploration, we predicted and verified the cancer-promoting effect of PFKFB3 in breast cancer complicated with hyperglycemia through RAS/MAPK pathway.ConclusionsIn conclusion, PFKFB3 could be overexpressed by hyperglycemia and might be a potential therapeutic target for breast cancer complicated with diabetes.

A degradome-based prognostic signature that correlates with immune infiltration and tumor mutation burden in breast cancer.

Female breast cancer is the most common malignancy worldwide, with a high disease burden. The degradome is the most abundant class of cellular enzymes that play an essential role in regulating cellular activity. Dysregulation of the degradome may disrupt cellular homeostasis and trigger carcinogenesis. Thus we attempted to understand the prognostic role of degradome in breast cancer by means of establishing a prognostic signature based on degradome-related genes (DRGs) and assessed its clinical utility in multiple dimensions. A total of 625 DRGs were obtained for analysis. Transcriptome data and clinical information of patients with breast cancer from TCGA-BRCA, METABRIC and GSE96058 were collected. NetworkAnalyst and cBioPortal were also utilized for analysis. LASSO regression analysis was employed to construct the degradome signature. Investigations of the degradome signature concerning clinical association, functional characterization, mutation landscape, immune infiltration, immune checkpoint expression and drug priority were orchestrated. Cell phenotype assays including colony formation, CCK8, transwell and wound healing were conducted in MCF-7 and MDA-MB-435S breast cancer cell lines, respectively. A 10-gene signature was developed and verified as an independent prognostic predictor combined with other clinicopathological parameters in breast cancer. The prognostic nomogram based on risk score (calculated based on the degradome signature) showed favourable capability in survival prediction and advantage in clinical benefit. High risk scores were associated with a higher degree of clinicopathological events (T4 stage and HER2-positive) and mutation frequency. Regulation of toll-like receptors and several cell cycle promoting activities were upregulated in the high-risk group. PIK3CA and TP53 mutations were dominant in the low- and high-risk groups, respectively. A significantly positive correlation was observed between the risk score and tumor mutation burden. The infiltration levels of immune cells and the expressions of immune checkpoints were significantly influenced by the risk score. Additionally, the degradome signature adequately predicted the survival of patients undergoing endocrinotherapy or radiotherapy. Patients in the low-risk group may achieve complete response after the first round of chemotherapy with cyclophosphamide and docetaxel, whereas patients in the high-risk group may benefit from 5-flfluorouracil. Several regulators of the PI3K/AKT/mTOR signaling pathway and the CDK family/PARP family were identified as potential molecular targets in the low- and high-risk groups, respectively. In vitro experiments further revealed that the knockdown of ABHD12 and USP41 significantly inhibit the proliferation, invasion and migration of breast cancer cells. Multidimensional evaluation verified the clinical utility of the degradome signature in predicting prognosis, risk stratification and guiding treatment for patients with breast cancer.

Evaluation oncotype DX® 21-gene recurrence score andclinicopathological parameters: a single institutional experience.

Oncotype DX recurrence score (RS) is a clinically validated assay, which predicts the likelihood of disease recurrence in oestrogen receptor-positive/HER2-negative (ER+/HER2-) breast cancer (BC). In this study we aimed to compare the performance of Oncotype DX against the conventional clinicopathological parameters using a large BC cohort diagnosed in a single institution. A cohort (n= 430) of ER+/HER2- BC patients who were diagnosed at the Nottingham University Hospitals NHS Trust and had Oncotype DX testing was included. Correlation with the clinicopathological and other biomarkers, including the proliferation index, was analysed. The median Oncotype DX RS was 17.5 (range=0-69). There was a significant association between high RS and grade 3 tumours. No grade 1BC or grade 2 tumours with mitosis score 1 showed high RS. Low RS was significantly associated with special tumour types where none of the patients with classical lobular or tubular carcinomas had a high RS. There was an inverse association between RS and levels of ER and progesterone receptor (PR) expression and a positive linear correlation with Ki67 labelling index. Notably, six patients who developed recurrence had an intermediate RS; however, four of these six cases (67%) were identified as high-risk disease when the conventional clinical and molecular parameters were considered. Oncotype DX RS is correlated strongly with the conventional clinicopathological parameters in BC. Some tumour features such as tumour grade, type, PR status and Ki67 index can be used as surrogate markers in certain scenarios.

Associations Between Serum Soluble Toll-like Receptors 4 and 9 and Breast Cancer in Egyptian Patients.

Toll-like receptors (TLRs) play an important role in regulation of immune cells and are vital in tumorigenesis due to its crucial role in inflammatory microenvironment regulation, as they promote the synthesis and release of inflammatory cytokines and chemokines. Toll-like receptors 4 and TLRs 9 were found to be highly expressed in breast cancer. The aim of this study is to investigate the soluble toll-like receptors 4 and 9 (sTLR4 and sTLR9) as potential biomarkers for diagnosis and prognosis of breast cancer and their association with the clinicopathological parameters of breast cancer. In this retrospective case-control study, 186 female subjects were recruited and divided into three groups, Group I: 62 healthy control, Group II: 62 subjects diagnosed with non-metastatic breast cancer, and Group III: 62 subjects diagnosed with metastatic breast cancer. Enzyme-linked immunosorbent assay (ELISA) technique was used to quantify the levels of sTLR4 and sTLR9 in serum. Both non-metastatic and metastatic groups showed significant higher levels of both serum sTLR4 and sTLR9 expression compared to healthy controls. Only sTLR9 was significantly increased among metastatic patients compared to non-metastatic group. Serum levels of sTLR9 and sTLR4 were still significantly associated with breast cancer in a multiple logistic regression model (P = <.001). ROC curves showed that both sTLR4 and sTLR9 can be a significant parameter to discriminate between normal females and breast cancer patients. Soluble toll-like receptors 4 and sTLR9 are over-expressed in patients with metastatic and non-metastatic BC than in benign cases. The expression levels of sTLR4 and TLR9 have clinical interest as indicators of tumor aggressiveness suggested to be prognostic biomarkers. Toll-like receptors may represent therapeutic targets in breast cancer.

P16 Expression in Human Breast Carcinoma and its Relationship to Clinicopathological Parameters.

p16 is a cyclin-dependent kinase inhibitor and a cardinal regulator of the cell cycle. The relationship between p16 overexpression and poor prognosis of breast cancer has been reported in some studies. This study aimed to evaluate p16 expression in breast cancer in comparison to normal breast tissue and determine the association between p16 expression and clinicopathological parameters in breast cancer. Paraffin blocks of 110 samples were studied. These included 40 invasive breast carcinoma (tumor group) and normal tissue adjacent to the tumor (tumor control), as well as 30 normal mammoplasty specimens (normal control). Samples were from the pathology archive of Alzahra Hospital, Isfahan, Iran, from 2016 to 2020. p16 expression was studied and compared in these three groups using the immunohistochemistry technique. Moreover, the relationship between p16 expression and age, tumor size, carcinoma subtype, tumor grade, and lymph node involvement was investigated in the tumor group. SPSS version 16 was used to analyze data. p16 expression showed a significant difference between the tumor group and the two control groups with a significantly higher expression in the tumor group. There was a significant direct relationship between the intensity of p16 expression and the number of involved lymph nodes (P < 0.001). No significant relationship was detected between p16 expression and other clinicopathological factors. p16 seems to have a rather significant expression in breast cancer in comparison to normal breast parenchyma. However, among clinicopathological parameters, we found only a direct relationship between lymph node involvement and intensity of p16 expression.

CD47 expression and tumor-associated immune cells in breast cancer and their correlation with molecular subtypes and prognostic factors.

Breast cancer is the most common malignancy in women and a heterogeneous disease at the molecular level. Since most breast cancer cases are not of a special type, it is suggested that tumor-associated macrophages and tumor-infiltrating lymphocytes, which are involved in tumor growth, invasion, angiogenesis, and metastasis, may be important factors that should be evaluated together with standard criteria to determine the prognosis of cancer and assist in treatment decisions and outcome stratification. In this study, CD47 expression, which is involved in macrophage-mediated immune escape, tumor-infiltrating lymphocytes, and tumor-associated macrophages were evaluated in breast cancer molecular subgroups and correlated with prognostic factors. The immunohistochemistry of CD47, CD163, and CD3 was analyzed on the tissue microarrays of 278 invasive breast cancer cases. The CD47, CD163, and CD3 expressions were found to be correlated with various clinicopathological parameters in breast cancer. High levels of CD47, CD163, and CD3 expressions had a significant correlation with the ER status and PR status, Ki-67 proliferation index, and molecular subtype (P<0.05). The CD47 expression had a significant correlation with the CD3 and CD163 expressions (p=0.021 and p=0.001, respectively). Our results suggest that CD47, CD163, and CD3 may be among the prognostic factors of breast cancer. The combined use of CD47, CD163, and CD3 can be a new prognostic factor for patients with breast cancer, especially as a therapeutic target in hormone receptor-negative breast cancer cases and those with a high proliferation index.

The role of exosomal survivin in the diagnosis of breast cancer

Breast cancer is the leading cause of death in women across the globe. The aim of this study is to compare exosomal survivin levels in breast cancer patients and healthy population. It is also to investigate the relationship between clinicopathological parameters of breast cancer and exosomal survivin levels. Patients who were diagnosed with histopathologically confirmed breast cancer and healthy volunteers were included in the study. Serum samples from patients and healthy volunteers were stored at -80℃. Exosomes were isolated from these serum samples. The integrity of the exosomes was disrupted. Survivin levels were measured by Enzyme Linked Immuno Sorbent Assay. Data on clinicopathological parameters were obtained from patient files and compared statistically.

Comprehensive analysis of the large and small ribosomal proteins in breast cancer: Insights on proteomic and transcriptomic expression patterns, regulation, mutational landscape, and prognostic significance

Several evidence has demonstrated the involvement of the ribosomal proteins (RPs) in many malignancies, however, the function and clinical relevance of the RPs in breast cancer remains unclear. The present study aims to contribute to the understanding of the role of the RPs in breast tumorigenesis and its clinical implications in the field of biomarker discovery and outcome prediction. We investigated the proteomic and transcriptomic expression of the RPs in non-tumor and tumor tissues of different breast cancer subtypes, and integrated bioinformatics approaches and online databases to comprehensively evaluate the potential functions, regulatory networks, mutational landscape, and prognostic values of the ribosomal proteins in breast cancer. Our results show that 33 RPs have deregulated expression in breast cancer and its subtypes and that 26 RPs have potential as prognostic markers in a subtype-dependent way, with mutations in RP genes being frequent in breast tumors and related to overall survival and relapse-free status. Our RP gene regulatory network indicates the transcription factors MYC, ETS1, and SPI1, and the miRNAs has-let-7c-5p, has-mir-20b-5p, and has-mir-4668–3p as regulators of the RPs expression in breast cancer. The RPs were associated with several clinicopathological parameters of breast cancer and predicted to be involved in ribosomal-independent mechanisms such as regulation of the SLITS-ROBO pathway. This study comprehensively investigated the ribosomal proteins in breast cancer, suggesting that the RPs have clinical potential as biomarkers of diagnostic and prognostic, also providing an in-depth view of the RPs significance in breast cancer.

Study of GATA-3 Expression in Breast Carcinoma in a Tertiary Care Hospital in Eastern India

Background: Transcription factor GATA3 is a relatively new and specific biomarker for breast carcinoma that regulates luminal cell differentiation. However, further studies that elucidate its role and diagnostic utility in breast cancer is desired. Therefore, this study was conducted to assess GATA3 expression in breast carcinoma and determine its association with various known prognostic and predictive factors of breast carcinoma. Methods: This is a cross-sectional, observational study where 110 breast carcinoma cases were examined histologically on H&amp;E stained slides for routine parameters such as tumor morphological type and histologic grade.ER/PR/Her-2-neu/ki67 and GATA3 expression was determined using immunohistochemistry. All cases were assessed to determine the association of GATA3 with different established clinicopathological parameters in breast cancer such as patient age, axillary lymph node status, tumor grade, lymphovascular invasion, molecular subtype etc. The results were statistically analyzed and P value &lt; 0.05 was considered to be significant. Results: 97 cases (88.1%) expressed GATA3 and it was significantly associated with most of the established clinico-pathological parameters like family history of breast cancer, tumour size and histology grade, lymph node and margin status, presence of lymphovascular invasion and carcinoma in-situ component .GATA3 expression was also significantly associated with ER/PR/Her2neu/ki67 expression. Conclusion: GATA3 expression is significantly associated with the different established clinicopathological parameters of breast cancer. Therefore, it may be considered as a relevant marker more routinely. Further studies of GATA3 in breast cancer may refine prognostic models, predict clinical outcomes and modify treatment guidelines in future

The prognostic importance of PD-L1, PTEN, PHH3, and KI-67 expressions in invasive breast carcinoma.

The aim of this study was to investigate the relationship of PD-L1, PTEN, PHH3, and Ki-67 immunohistochemical stain expressions with prognostic clinicopathological parameters in breast cancer. Lumpectomy and mastectomy materials from 85 patients operated at the Department of Pathology, Bolu Abant Izzet Baysal University, Faculty of Medicine between 2014 and 2019 were retrospectively reviewed. PD-L1, PTEN, PHH3, and Ki-67 expressions were examined. Immunohistochemical staining results were compared with clinicopathological parameters and found to be associated with prognosis. A statistically significant correlation was found between PD-L1 and large tumor size, high histological grade, multifocality, and lymphovascular invasion. A statistically significant correlation was found between the loss of PTEN and large tumor size and histological grade. There was a statistically significant correlation between PHH3 and advanced age, large tumor size, and high histological grade. A statistically significant correlation was found between Ki-67 and large tumor size, high histological grade, and lymphovascular invasion. PD-L1, PTEN, PHH3, and Ki-67 are regarded as potential biomarkers that can be used to predict the prognosis of breast cancer and to develop targeted therapies.

Expression of tissue PSA in breast cancer is associated with less aggressive disease and lower chance of tumor relapse

Background: Human kallikrein 3 (hK3), also known as Prostatic specific antigen (PSA), was considered as one of the most useful markers for the detection as well as management of prostate cancer. While PSA was thought to be a prostatic tissue-specific protein, many reports suggest the presence of extraprostatic PSA in different tissues, including the breast. Few reports showed PSA immunoreactivity in breast cancer tissues and suggest a favorable prognostic role of PSA in breast cancer. However, most of those studies were not conclusive or restricted to small scale studies limiting their clinical significance. Methods: We used a bioinformatical approach to investigate the association between tissue PSA expression levels and different clinicopathological parameters in breast cancer using different publicly available databases. Further validation was done using our patient cohort of 40 surgical breast samples obtained from patients attending Al Kadhemyia Teaching Hospital – Iraq. Results: Using a cohort of 593 breast lesion samples extracted from the TCGA database using the ONCOMINE database, our results showed no significant upregulation of PSA mRNA levels in breast cancer samples compared to healthy tissue (P = 0.1). The same trend was also observed in our patient cohort with positive immunoreactivity in 50% (5 samples) of benign lesions compared to 36.66% (11 samples) in breast cancer samples. In addition, investigating the correlation between mRNA PSA expression and different clinicopathological parameters using the Breast Cancer Gene-Expression Miner v4.0 database and ONCOMINE databases, revealed a significant association between PSA expression and tumor grade (P = 0.0001), breast cancer subtype (P < 0.0001), in addition to early-stage disease presented as smaller tumor size and absence of LN involvement. The same trend confirmed with our patient cohort. Moreover, our analysis using KM plotter (4000 breast cancer samples) showed a significant association between higher PSA mRNA levels and favorable patient outcomes presented as prolonged relapse-free survival (RFS) (P < 0.0001). Conclusions: Our results clearly demonstrate the possibility of using tissue mRNA and protein levels of PSA as a marker to identify patients with a favorable outcome and lower risk of tumor recurrence. Our results also highlight the need for more efforts to investigate the biological role of PSA in breast cancer.

Expression of Poly(Adenosine Diphosphate-Ribose) Polymerase Protein in Breast Cancer.

The use of poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors for breast cancer (BC) therapy is the subject of debate, and there is an urgent need to understand much the expression and prognostic role of the PARP1 protein. In this study, we have compared the expression of PARP between BC and benign breast disease (BBD) patients and also analyzed the association of PARP expression with clinicopathological parameters in BC. The study consists of 30 patients with newly diagnosed operable BC who were planned for surgery without neoadjuvant chemotherapy and 15 patients of BBD as a control between 2019 and 2021. Immunohistochemical analyses were performed prospectively on tissue samples. Anti-human PARP1 rabbit polyclonal antibody gives strong nuclear positivity. Internal control was the adipose tissue and the BBD acted as the external control. PARP1 expression was evaluated using the multiplicative quickscore method. The mean age for BC patients was 51.30 ± 10.694 years (range: 25-75 years) while BBD was below 30 years. Overexpression of PARP was present in 25 (83.3%) and weak expression in 5 (16.7%) of BC patients compared to BBD, only 2 (13.3%) patients demonstrated an overexpression of PARP, and 13 (86.6%) patients showed weak expression which showed significant association (P < 0.001). In BC, nuclear PARP (nPARP) overexpression was seen in 22 (73.3%) patients and weak expression of nPARP in 8 (26.7%), whereas 5 (16.7%) patients showed cytoplasmic overexpression. On comparing expression of PARP with clinicopathological parameters, PARP overexpression was significantly associated with older population (age >50 years) (P = 0.002), postmenopausal women (P = 0.029), higher TNM stage (Stage II and III) (P = 0.014), higher histological grade (grade 2) (P = 0.043), and presence of lymphovascular invasion (P = 0.015). Enhanced PARP1 expression is closely correlated with positive estrogen receptor status (P = 0.001) and PR status (P = 0.001). Overall PARP and nPARP overexpression was significantly associated with ER- (P = 0.006 and P = 0.008) and PR-positive (P = 0.006 and P = 0.008) patients. The PARP and nPARP overexpression was significantly associated with nontriple-negative BC patients (P = 0.001 and P = 0.001). We have not come across any study in the literature to compare PARP expression in BC and BBD patients. On the basis of our observations, we concluded that PARP overexpression is a poor prognostic marker in BC.

The Oncogenic Roles of JC Virus T Antigen in Breast Carcinogenesis.

Purpose: JC virus (JCV) infects 80–90% of the population and results in progressive multifocal leukoencephalopathy upon immunodeficiency. The study aimed to pathologically clarify the oncogenic roles of T antigen in human breast cancers.Methods: Breast cancer, dysplasia, and normal tissues were examined for T antigen of JCV by nested and real-time PCR. The positive rate or copy number of T antigen was compared with clinicopathological parameters of breast cancer. JCV existence was morphologically detected by immunohistochemistry and in situ PCR. T antigen was examined by Western blot using frozen samples of breast cancer and paired normal tissues.Results: According to nested PCR, the positive rate of breast ductal or lobular carcinoma was lower than that of normal tissue (p < 0.05). T antigen existence was negatively correlated with E-cadherin expression and triple-negative breast cancer (p < 0.05), but positively correlated with lymph node metastasis and estrogen receptor and progestogen receptor expression (p < 0.05). Quantitative PCR showed that JCV copies were gradually decreased from normal, dysplasia to cancer tissues (p < 0.05). JCV T antigen copy number was lower in ductal adenocarcinoma than in normal tissue (p < 0.05), in line with in situ PCR and immunohistochemistry. JCV copies were negatively correlated with tumor size and E-cadherin expression (p < 0.05), but positively correlated with G grading of breast cancer (p < 0.05). Western blot also indicated weaker T antigen expression in breast cancer than normal tissues (p < 0.05).Conclusion: JCV T antigen might play an important role in breast carcinogenesis. It can be employed as a molecular marker for the differentiation and aggressive behaviors of breast cancer.

CORRELATION OF GATA-3, E-CADHERIN, P53 AND KI-67 EXPRESSION WITH HISTOLOGICAL TYPE/MOLECULAR SUBTYPE AND CLINICOPATHOLOGICAL PARAMETERS IN BREAST CANCER

Aims&#x0D; The purpose of our study is to examine immunohistochemically the correlation of GATA binding protein 3 (GATA3), E-cadherin, p53 and Ki-67 expression with histological type/molecular subtype and clinicopathological parameters in breast cancer. &#x0D; Methods and results&#x0D; 120 patients diagnosed with breast cancer were retrospectively investigated between 2018 May and 2021 January. We used the GATA3, E-cadherin, P53, Ki67 antibody by immunohistochemical analysis in breast tumors. GATA3 was positive in 100% (107/107) of the luminal A, luminal B and HER2 overexpressing groups and 79.9% (10/13) of the triple negative (TN) group. It is less common in the TN group (p 20% was higher in human epidermal growth factor receptor 2 (HER2) overexpressing and TN groups compared to luminal A and luminal B subtypes (p

Expression of long-form prolactin receptor is associated with lower disease-free and overall survival in node-negative breast cancer patients

Breast cancer is the most frequent female malignancy in Thailand. Prolactin (PRL) and prolactin receptor (PRLR) play an important role in normal breast development and carcinogenesis of breast cancer. There are two major isoforms of PRLR, consisting of long-form (LF-PRLR) and short-form (SF-PRLR) that stimulate different signaling pathways. This study aims to explore the associations between all PRLR isoforms (all-PRLR) and LF-PRLR with clinicopathological parameters in breast cancer patients. A total of 340 patients were recruited from January 2009 to December 2015. Expressions of PRLR in breast cancer tissue were determined by immunohistochemistry using specific antibodies that recognize different domains of PRLR (B6.2 for all-PRLR and H-300 for LF-PRLR). The associations between all-PRLR and LF-PRLR expressions with clinicopathological parameters were evaluated. Expression of all-PRLR was observed in 86.2% of all patients while LF-PRLR expression was observed in 54.4%. All-PRLR was co-expressed with estrogen receptor (ER) and progesterone receptor (PR). LF-PRLR expression was associated with high grade tumor and human epidermal growth factor receptor-2 (HER2) overexpression (P=0.010 and <0.001, respectively). Subgroup analysis revealed that LF-PRLR expression was the independent predictor for lower disease-free survival (DFS) in node-negative breast cancer patients with high expression of all-PRLR [hazard ratio (HR): 5.224, 95% confidence interval (CI): 1.089-25.064, P=0.039]. The presence of LF-PRLR in the patients with high expression of all-PRLR was associated with adverse outcome. Evaluation of all-PRLR and LF-PRLR might be used as novel prognosticators in node-negative breast cancers.

Correlation between numerical and categorical immunohistochemical score of Ki-67 and HER2 with clinicopathological parameters of breast cancer.

Aim To evaluate the relationship between numerical and categorical immunohistochemical score of Ki-67 and human epidermal growth factor of receptor 2 (HER2) with clinicopathological parameters of breast cancer (BC). Methods The study included 311 patients with invasive BC diagnosed at the Department of Pathology, School of Medicine in Sarajevo, Bosnia and Herzegovina, during the period 2015-2019. The expression level of Ki-67 and HER2 was detected by immunohistochemical analysis. Results The expression of Ki-67, as a numerical variable correlated significantly with tumour grade (p=0.025), progesterone receptor (PR) (p=0.034) and categorical score of HER2 (p=0.028). When Ki-67 was categorized into high (>14%) and low (≤14%) level groups, a statistically significant association was found between Ki-67 level groups and HER2 status (categorical and numerical) (p=0.001 and p=0.043, respectively), as well as significant negative linear correlation with PR (p=0.037). The expression of HER2, as a numerical variable, showed a statistically significant correlation with tumour grade (p=0.038), PR (p=0.025) and categorical Ki-67 (p=0.043). Categorical score of HER2 correlated significantly with age (p=0.025), histologic type (p=0.039), tumour grade (p=0.016), estrogen receptor (ER), (p=0.002) progesterone receptor (PR) (p=0.0001), and categorical and numerical value of Ki-67 (p=0.0001 and p=0.0001, respectively). Conclusion The results demonstrated that the categorical immunohistochemical score of HER2 provided a greater association with clinicopathological parameters than numerical score of BC. Furthermore, a slightly better correlation with clinicopathological parameters was shown by the numerical value than by the categorical score of Ki-67 by applying a cut-off value of 14%.

The Clinical Relevance and Function of Krüppel-Like Factor 16 in Breast Cancer.

BackgroundKrüppel-like factor 16 (KLF16), a member of the KLF family, is involved in metabolism and regulation of the endocrine system and has emerging roles in tumor progression. However, the expression of KLF16 and its role in breast cancer are elusive.MethodsWe investigated the expression and prognostic value of KLFs in breast cancer using data acquired from the TCGA BRCA dataset and the Kaplan–Meier plotter dataset. The protein levels of KLF16 in breast specimens were detected by immunohistochemistry (IHC). KLF16 silencing using shRNAs was performed to explore the effects of KLF16 on breast cancer cell growth, migration, and invasion. The expression of EMT markers in cells manipulated for KLF16 expression was assessed by Western blotting.ResultsUsing publicly available dataset and specimens from breast cancer patients, we found that the expression levels of KLF16 were significantly higher in tumor tissues and that high levels of KLF16 were associated with poor prognosis in breast cancer patients. Moreover, KLF16 expression levels had relation to several clinicopathological parameters of breast cancer, including the molecular subtype and histological grade. Importantly, knockdown of KLF16 dramatically suppressed cell proliferation both in vitro and in vivo. Also, KLF16 deletion impaired migration, and invasion in breast cancer cells, and suppressed epithelial–mesenchymal transition (EMT).ConclusionOur results suggest that KLF16 has important oncogenic functions in breast cancer and that the expression levels of KLF16 are associated with prognosis in breast cancer patients. Our findings also suggest that KLF16 is involved in proliferation, migration, and invasion in breast cancer cells. Thus, KLF16 might be a promising prognostic marker and a therapeutic target for breast cancer.