Prognosis Of Breast Carcinoma Research Articles

A STUDY OF OCT3/4 EXPRESSION IN HER2/NEU POSITIVE BREAST CANCER PATIENTS

Oct3/4 is found in germ cells is crucial to control pluripotency during normal development. There is mounting evidence for an association between Oct3/4 and carcinogenesis. Thus Oct3/4 immunohistochemistry has been found in studies to be a useful diagnostic technique for pluripotent germ-cell cancers, providing fresh insights into the cancer's histological heterogeneity. The aim is to study role of Oct3/4 expression in HER2/neu positive breast cancer patients. Paraffin embedded breast tumour tissues from 50 HER2/neu positive female breast cancer patients were enrolled in the study. Oct3/4 expression was studied by immunohistochemistry method and correlated with clinical and pathological parameters as well as disease status. Oct3/4 positivity was seen in 16% of HER2/neu positive breast cancer patients. No significant correlation of Oct3/4 expression with age, menopausal status, tumour size, histopathology, grade and BR score was observed. A trend of higher incidence of Oct3/4 expression was noted with lymph node positive (30%) than lymph node negative patients (07%). A significant higher incidence of Oct3/4 expression was noted in patients with advanced stage of disease (32%) as compared to patients with early stage of disease (04%) and in patients with relapse (44%) than patients in remission (10%). A significant higher incidence Oct3/4 expression was observed with respect to disease free survival in univariate survival analysis. In multivariate survival analysis, for disease free survival metastasis entered at step 1 and grade entered at step 2. For overall survival, metastasis is entered at step 1 as significant factor. The Oct3/4 gene expression may be implicated in self-renewal and tumorigenesis via activating its downstream target genes. It might serve as an important biomarker for contemplating the carcinogenesis, progression, metastasis, or invasive potential and prognosis of breast carcinoma. A larger prospective follow-up studies are recommended to further explore Oct3/4 significance.

Overexpression of HMGB3 and its prognostic value in breast cancer.

High mobility group protein B3 (HMGB3) is abundantly expressed in a number of malignancies, contributing to tumor cell growth and predicting poor outcomes. More research on the connection between HMGB3 and breast cancer is needed. The prognostic significance of HMGB3 in breast cancer was examined and validated in this study. Using The Cancer Genome Atlas (TCGA) database RNA sequencing and clinical data, we investigated the associations between HMGB3 expression and tumor mutations, prognosis, and immune infiltration in breast cancer. The Gene Expression Profiling Interactive Analysis (GEPIA), Tumor Immune Estimation Resource (TIMER), breast cancer gene-expression miner (bc-GenExMiner), UALCAN, OncoLnc, cBio Cancer Genomics Portal (cBioPortal), and LinkedOmics databases were applied to examine the levels of expression, mutation, coexpression, and immune correlation of HMGB3 in breast cancer. cBioPortal and the Database for Annotation, Visualization, and Integrated Discovery (DAVID) were used for coexpression and enrichment analyses, respectively. Experimental tests and a separate cohort of breast cancer patients in our center were used for validation. To determine independent risk factors affecting breast carcinoma prognosis, multivariate Cox regression analysis was performed. The Kaplan-Meier method was applied to analyze the connection between HMGB3 expression and overall survival time in breast cancer. Pan-cancer investigation using the GEPIA and UALCAN databases revealed a high level of HMGB3 expression in different malignancies, including breast cancer. HMGB3 might be a potential diagnostic biomarker, according to the receiver operating characteristic (ROC) curve (AUC=0.932). And immunohistochemistry confirmed higher HMGB3 protein expression in breast cancer tissues in clinical samples. Experimental tests also showed that breast cancer cells have higher expression of HMGB3, and knockdown of HMGB3 can promote the proliferation of breast cancer cells and increase sensitivity to chemotherapy. Human epidermal growth factor receptor 2 (HER2), Nottingham Prognostic Index (NPI), basal-like status, nodal status (N+), triple-negative status, and Scarff-Bloom-Richardson (SBR) grade all showed positive correlations with HMGB3 expression. Conversely, HMGB3 expression was negatively associated with the expression of estrogen receptor (ER) and progesterone receptor (PR) in breast cancer. Breast cancer patients with high HMGB3 expression had poor overall survival, which was validated by an analysis of a separate cohort of breast cancer patients in our center. Cox regression analysis identified high HMGB3 expression as an independently associated risk factor for breast carcinoma. The amount of immunological infiltration was substantially linked with the high expression of HMGB3. The chromosome centromeric region, ATPase activity, and the cell cycle are critical areas where HMGB3 is involved, according to enrichment analysis. Therefore, we suspected that HMGB3 might be a potential biomarker for detecting and treating breast carcinoma. Breast cancer tissues had higher HMGB3 expression than normal breast tissues. HMGB3 overexpression may serve as an indicator for poor breast cancer outcomes.

Circulatory RNA based non-invasive detection and diagnosis of breast cancer

Breast carcinoma is the most prevalent and lethal form of carcinoma in women, as well as the most prominent source of cancer-related mortality in women. The most widespread form of non-invasive breast carcinoma is ductal carcinoma in situ (DCIS). Early detection of breast carcinoma improves the chances of rehabilitation and survival, lowering mortality rates. Limitations of mammography as a screening test have made it imperative to develop new, non-invasive, and more convenient alternatives for the prognosis of breast carcinoma. Circulatory RNAs (miRNAs) have been included in a novel category of non-coding, endogenous, small RNA fragments that can be considered gene expression regulators, influencing key processes in cancer development. Peculiar expressions and firmness of circulatory RNAs exhibit a promising possibility of their use as biomarkers in the prognosis of mammary tumor.

The presentation, management and outcome of patients with ductal carcinoma in situ (DCIS) with microinvasion (invasion ≤1 mm in size)—results from the UK Sloane Project

BackgroundThe diagnosis, management and prognosis of microinvasive breast carcinoma remain controversial.MethodsWe analysed the outcomes of patients with DCIS with and without microinvasion diagnosed between 2003 and 2012 within the Sloane project.ResultsMicroinvasion was recorded in 521 of 11,285 patients (4.6%), with considerable variation in reported incidence among screening units (0–25%). Microinvasion was associated with high-grade DCIS, larger DCIS size, comedo necrosis and solid, cribriform architecture (all P < 0.001). Microinvasion was more frequent in patients who underwent mastectomy compared with breast-conserving surgery (BCS) (6.9% vs 3.6%, P < 0.001), and in those undergoing axillary nodal surgery (60.4% vs 30.3%, P < 0.001) including the subset undergoing BCS (43.4% vs 8.5%, P < 0.001). Nodal metastasis rate was low and not statistically significant difference from the DCIS only group (P = 0.68). Following median follow-up of 110 months, 3% of patients had recurrent ipsilateral high-grade DCIS, and 4.2% developed invasive carcinoma. The subsequent ipsilateral invasion was of Grade 3 in 71.4% of patients with microinvasion vs 30.4% in DCIS without microinvasion (P = 0.02). Distant metastasis and breast cancer mortality were higher with microinvasion compared with DCIS only (1.2% vs 0.3%, P = 0.01 and 2.1% vs 0.8%; P = 0.005).ConclusionsThe higher breast cancer mortality with microinvasion indicates a more aggressive disease.

116P Expression of Her2/Neu and Ki-67 proliferation index in gall bladder carcinomas: Clinicopathological significance

Gall bladder carcinomas (GBC) are one of the most common and aggressive biliary tract malignancies causing significant mortality in South-East Asia and South America as a result of advanced stage at presentation, early metastases, and poor outcomes with standard chemotherapy. Overexpression of Her2/Neu is associated with poor prognosis in breast and gastric carcinomas, which is also being studied for GBC. Ki 67 proliferation index, a marker of replicative potential, is high in higher-grade and aggressive tumors.

Increased expression of SYCP2 predicts poor prognosis in patients suffering from breast carcinoma.

Overexpression of synaptonemal complex protein-2 (SYCP2) has been identified in various human papillomavirus (HPV)–related carcinomas, whereas its significant role in breast carcinoma remains unclear. The aim of this study was to elucidate the prognostic value and potential function of SYCP2 in breast carcinoma. Herein, data for breast carcinoma patients from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas database (TCGA) were analyzed. The enrichment analysis of SYCP2 including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Friends, and GSEA was performed. Kaplan–Meier analysis, Cox regression, and receiver operating characteristic (ROC) curves were employed for determining the predictive value of SYCP2 on clinical outcomes in patients suffering from breast carcinoma. A nomogram was generated to predict the effect arising from SYCP2 on prognosis. The association analysis of SYCP2 gene expression and diverse immune infiltration levels was conducted through ssGSEA and ESTIMATE analysis, which consisted of dendritic cell (DC), neutrophil, eosinophil, macrophage, mast cell, NK cell, and other 18 cell subtypes. The results showed that SYCP2 expression was significantly elevated in breast carcinoma tissues as compared with that of normal tissues (p < 0.001). SYCP2 plays a certain role in pathways related to DNA methylation, keratinocyte differentiation, steroid hormone biosynthesis, and immune infiltration. The high expression of SYCP2 had a significant relationship to age, pathological type, ER expression, and PR expression (p < 0.001). Kaplan–Meier survival analysis showed that patients suffering from breast carcinoma characterized by high-SYCP2 expression had a poorer prognosis than patients with low-SYCP2 expression (p = 0.005). Univariate and multivariate Cox regression analyses revealed that SYCP2 had an independent relationship to overall survival (p = 0.049). Moreover, ROC curves suggested the significant diagnostic ability of SYCP2 for breast carcinoma, and as time went on, SYCP2 had more accurate prognostic efficacy. Furthermore, a high level of SYCP2 expression was found to have a relationship to poor prognosis of breast carcinoma in the subgroups of T3, N0, and M0, and infiltrating ductal carcinoma (HR > 1, p < 0.05). The calibration plot of the nomogram indicated that the SYCP2 model has an effective predictive performance for breast carcinoma patients. Conclusively, SYCP2 plays a vital role in the pathogenesis and progression of human breast carcinoma, so it may serve as a promising prognostic molecular marker of poor survival.

Differences of Clinicopathological Features between Metaplastic Breast Carcinoma and Nonspecific Invasive Breast Carcinoma and Prognostic Profile of Metaplastic Breast Carcinoma.

Introduction Metaplastic breast carcinoma is a rare special type of breast cancer, which has distinguished clinical characteristics. We aimed to evaluate the clinicopathological features of metaplastic breast carcinoma compared with nonspecific invasive breast carcinoma and study the prognosis of metaplastic breast carcinoma. Methods We reviewed metaplastic breast carcinoma cases (n = 37) from January 2000 to December 2021 and nonspecific invasive breast carcinoma cases (n = 433) from January 2019 to December 2020 extracted from our institution retrospectively. The following variables were recorded, including the patients' general information, complications, T stage, expression of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, Ki-67, molecular subtyping, lymph node status, skin or chest wall involvement, vessel carcinoma embolus, therapy modality (surgical treatments, chemotherapy, and radiotherapy), and survival. Results Patients with metaplastic breast carcinoma had more advanced disease than patients with nonspecific invasive breast carcinoma (T stage: P=0.0011). A greater proportion of metaplastic breast carcinoma presented with triple-negative breast cancer than nonspecific invasive breast carcinoma (79.41% vs. 12.47%, P ≤ 0.001). Our study showed that the skin or chest wall invasion was more frequent in metaplastic breast carcinoma patients (11.76% vs. 1.62%, P=0.005). The 5-year survival rate for metaplastic breast carcinoma patients was 57.66% (95% CI: 0.3195∼0.7667). No local recurrence was observed while distant metastasis occurred in 33.33% of patients with metaplastic breast carcinoma. Death due to disease occurred in 24.24% of patients with metaplastic breast carcinoma. Conclusion The majority of metaplastic breast carcinoma patients had more advanced disease and triple-negative disease than nonspecific invasive breast carcinoma patients. Also, metaplastic breast carcinoma patients had frequent skin or chest wall invasion and a high rate of distant metastasis and mortality.

Histological and Clinical Stage Profiles of Young-aged Breast Carcinoma

Background: Breast cancer is the most common type of malignancy in women. Many studies report that the characteristics and prognosis of young-aged breast carcinoma are worse than in old age. Data on young-aged breast carcinoma in Indonesia is relatively lacking and always needs updates.Objective: To determine the incidence and distribution based on histological profiles and clinical stage, as well as the association between molecular subtype with grade and clinical stage of young-aged breast carcinoma (&lt;40 years old) at Dr. Kariadi General Hospital Center in 2018-2020.Methods: This research was an observational descriptive study using medical records of young-aged breast carcinoma patients which were recorded at Dr. Kariadi General Hospital Center from 1st January 2018 until 31st December 2020. The data were processed with Microsoft Excel and SPSS.Results: The results showed that there were 110 patients consisting of 25 people in 2018, 37 people in 2019, and 48 people in 2020. The most common histological and clinical stage was IBC-NST with 75 people (68,18%), Luminal B with 53 people (48,18%). grade II with 71 people (64,65%), and stage IV with 45 people (40,09%). There is a significant association between molecular subtype and grade (p=0.003). There is no significant association between molecular subtype and clinical stage (p=0.704).Conclusion: The incidence of young-aged breast carcinoma at Dr. Kariadi General Hospital Center in 2018-2020 was increasing every year. The most common histological profiles and clinical stage during that period were IBC-NST, Luminal B, grade II, and stage IV. There is a significant association between molecular subtype and grade.Keywords: Breast carcinoma, clinical stage, grade, histological type, molecular subtype, young age

The expression landscape of FOXP3 and its prognostic value in breast cancer.

BackgroundForkhead Box Protein 3 (FOXP3), as an essential marker of regulatory T cell (Treg) development, is reportedly overexpressed in invasive breast carcinoma (BRCA) and could be a potential prognostic factor for BRCA. However, the biological function of FOXP3 in BRCA is still unclear. In this study, we comprehensively explored the expression landscape of FOXP3 and its prognostic value in BRCA.MethodsFOXP3 transcriptomic expression data were mainly obtained from The Cancer Genome Atlas (TCGA). The Kaplan-Meier plotter and receiver operating characteristic (ROC) curve were used to assess the prognostic and diagnostic value of FOXP3 in BRCA. UALCAN, cBio-Portal, and MethSurv were used to evaluate the genomic variation of FOXP3. Gene set enrichment analysis (GSEA) was performed to explore the FOXP3 pathways involved in BRCA. Morover, we detected the expression of FOXP3 in 123 BRCA specimens and 5 BRCA cell lines to verify the biological value of FOXP3 in BRCA. The Kaplan-Meier method was adopted for the overall survival (OS) analysis, and a Cox proportional hazards model was used to estimate the hazard ratio (HR) for OS.ResultsFOXP3 was more highly expressed in BRCA than in normal tissues (2.808±1.020 vs. 1.409±0.656, P<0.001), and overexpressed FOXP3 was associated with a better prognosis. The ROC curve demonstrated a significant diagnostic value of FOXP3 in BRCA (area under the ROC curve, AUC: 0.877). Genomic analysis revealed that promoter hypomethylation of FOXP3 may be the underlying mechanism of FOXP3’s upregulation in BRCA. GSEA found that FOXP3 coexpressed genes were mainly involved in the Toll-like receptor pathway, JAK/STAT pathway, cell cycle, and apoptosis. Moreover, high FOXP3 expression was an independent protective factor for OS in our 123 BRCA tissues (HR: 0.367; P=0.036). In vitro, we found that FOXP3 knockdown with siRNA promoted migration and invasion in MCF-7 cells.ConclusionsThis study demonstrated that FOXP3 shows prognostic and diagnostic value for BRCA. We provided evidence that promoter hypomethylation and a high expression of FOXP3 were both related to a favorable prognosis in BRCA, which maybe associated with the Toll-like receptor pathway, JAK/STAT pathway, cell cycle, and apoptosis.

Investigating CENPW as a Novel Biomarker Correlated With the Development and Poor Prognosis of Breast Carcinoma.

Breast invasive carcinoma (BRCA) is a carcinoma with a fairly high incidence, and the therapeutic schedules are generally surgery and chemotherapy. However, chemotherapeutic drugs tend to produce serious toxic side effects, which lead to the cessation of treatment. Therefore, it is imperative to develop treatment strategies that are more effective and have fewer side effects at the genetic level. Centromeric protein W (CENPW) is an oncogene that plays an important part in nucleosome assembly. To date, no studies have reported the prognostic significance of CENPW in breast carcinoma. In this study, we verified that CENPW expression is up-regulated in breast carcinoma and positively associated with the level of immune cell infiltration. The clinicopathological characteristics further suggest that CENPW expression is correlated with a worse prognosis of breast carcinoma. Interestingly, the CENPW mutation contributes to the poor prognosis. Next, we discovered that the genes interacting with CENPW are mainly concentrated in the cell cycle pathway, and CENPW is co-expressed with CDCA7, which is also highly expressed in breast carcinoma and leads to a worse prognosis. Our subsequent studies verified that knockdown of CENPW significantly inhibits the proliferation and migration of breast carcinoma cells and promotes their apoptosis rate. Notably, inhibition of CEMPW sensitizes breast cancer cells to chemotherapeutic drugs that have been found to induce cell cycle arrest. In summary, these results provide extensive data and experimental evidence that CENPW can serve as a novel predictor of breast cancer and may act as a prospective therapeutic target.

Study of estrogen receptor, progesterone receptor, and HER-2/neu status in breast carcinoma

Background: Breast cancer treatment depends mainly on hormone receptors (estrogen and PRs) and human epidermal growth factor receptor-2 (HER2)/neu profile. These receptor analyzes determine the patient’s prognosis, treatment, and outcome. Aims and Objectives: The main objective of this study was to correlate the histologic grade of breast carcinoma with hormone receptors and HER2/neu status. Materials and Methods: This is a retrospective analysis of 342 patients treated from January 2016 to December 2021 at Manipal Teaching Hospital, Pokhara, Nepal to determine hormone receptors and HER2/neu status in breast carcinoma. Modified radical mastectomy, breast-conserving surgery, toilet mastectomy, and excisional biopsies were included for statistical correlation between hormone receptors, HER2/neu, histologic grade, and lymph node status. Results: The mean age of the patients was 48.43±9.4 years (29–71). Of the 342 patients, 334 (97.7%) were female and 8 (2.3%) were male. Left breast carcinoma was 5.3% more common than right breast carcinoma. Among them, 34 (9.9%), 245 (71.6%), and 63 (18.4%) were grade I, II, and III, respectively. Grade II were the most common cancer. The smallest tumor size was 0.5 cm and the largest tumor size was 14 cm. Lymph node involvement was 226 (66.1%). The most common histology was invasive ductal carcinoma with 282 (82.5%), lobular carcinoma with 47 (13.8%), medullary carcinoma with 9 (2.6%), and mucinous carcinoma with 4 (1.2%). Immunohistochemical analysis of all breast cancer patients in the present study revealed ER 175 (51.2.7%), PR 146 (42.7%), and HER2/neu 93 (27.2%). Of all male patients, ER was 100% positive, PR was 75% positive, and HER2/neu was 25% positive. According to grading, ER was seen positive in 23 (13.1%) in grade I, 112 (64%) in grade II, and 40 (22.8.1%) in grade III carcinoma (P&lt;0.05). Similarly, PR was 19 (13.1%) in grade I, 95(65.9%) in grade II, and 30 (20.8%) in grade III carcinomas (P&lt;0.05). Moreover, Her/2-neu was 7 (7.5%) in grade I, 63 (67.3%) in grade II, and 23 (24.7%) in grade III carcinomas (P&lt;0.05). In HER2/neu positive cases, it was observed that the positive expression of estrogen receptor (ER) was high as compared to PR. Conclusion: ERs, PRs, and HER2/neu are the most important factors that determine the best treatment, prognosis, and outcome in breast carcinoma.

Regulation of GPCR‐induced Hippo pathway signaling by ARRDC3 in breast carcinoma

G protein‐coupled receptors (GPCRs) are a large and diverse family of cell surface receptors implicated in cancer progression. In particular, overexpression of the GPCR protease‐activated receptor‐1 (PAR1) is associated with poor patient prognosis and metastasis of breast carcinoma. However, there remains a critical gap in knowledge of how PAR1 expression leads to breast cancer progression. Recently, the alpha‐arrestin, arrestin domain‐containing protein 3 (ARRDC3), was identified as a tumor suppressor in invasive breast carcinoma. In non‐invasive cells, ARRDC3 is essential for PAR1 trafficking and lysosomal degradation. However, ARRDC3 expression is lost in invasive breast carcinoma, resulting in dysregulated PAR1 trafficking and persistent signaling that promotes invasive breast cancer progression. Re‐expression of ARRDC3 in invasive breast carcinoma is sufficient to restore PAR1 lysosomal degradation and normal signaling, and thereby suppresses breast cancer invasion and metastasis. Moreover, ARRDC3 regulates PAR1‐stimulated Hippo pathway signaling independent of its function in regulating receptor trafficking. The Hippo pathway is driven by the activity of two transcriptional co‐activators: yes‐associated protein (YAP) and transcriptional co‐activator with PDZ‐binding motif (TAZ), and is linked to cancer progression. ARRDC3 regulates GPCR‐induced Hippo pathway signaling by binding and sequestering TAZ in the cytoplasm, thus preventing nuclear translocation and transcription of genes associated with tumor metastasis and progression. Thus, ARRDC3 exhibits multiple tumor suppressor activities to control GPCR signaling in breast cancer. However, it remains unclear how GPCR activation regulates ARRDC3 function to control Hippo pathway signaling in invasive breast cancer. Here, I will present studies that interrogate various mechanisms by which GPCRs regulate Hippo pathway signaling. The results of these studies will define fundamental mechanisms by which GPCRs promote breast cancer progression via Hippo pathway signaling and vital regulatory mechanisms of the Hippo pathway that may lead to the development of new and effective therapies.

BRCA1/2 Serves as a Biomarker for Poor Prognosis in Breast Carcinoma.

BRCA1/2 are breast cancer susceptibility genes that are involved in DNA repair and transcriptional control. They are dysregulated in breast cancer, making them attractive therapeutic targets. Here, we performed a systematic multiomics analysis to expound BRCA1/2 functions as prognostic biomarkers in breast cancer. First, using different web-based bioinformatics platforms (Oncomine, TIMER 2.0, UALCAN, and cBioportal), the expression of BRCA1/2 was assessed. Then, the R package was used to analyze the diagnostic value of BRCA1/2 in patients. Next, we determined the relationship between BRCA1/2 mRNA expression and prognosis in patients (PrognoScan Database, R2: Kaplan Meier Scanner and Kaplan–Meier Plotter). Subsequently, the association of BRCA1/2 with mutation frequency alteration and copy number alterations in breast cancer was investigated using the cBioportal platform. After that, we identified known and predicted structural genes and proteins essential for BRCA1/2 functions using GeneMania and STRING db. Finally, GO and KEGG pathway enrichment analyses were performed to elucidate the potential biological functions of the co-expression genes of BRCA1/2. The BRCA1/2 mRNA level in breast cancer tissues was considerably higher than in normal tissues, with AUCs of 0.766 and 0.829, respectively. Overexpression of BRCA1/2 was significantly related to the worse overall survival (p < 0.001) and was correlated to clinicopathological characteristics including lymph nodes, estrogen receptors, and progesterone receptors (p < 0.01). The alteration frequencies of both the gens have been checked, and the results show that BRCA1 and BRCA2 show different alteration frequencies. Their mutation sites differ from each other. GO and KEGG showed that BRCA1/2 was mainly enriched in catalytic activity, acting on DNA, chromosomal region, organelle fission, cell cycle, etc. The 20 most frequently changed genes were closely related to BRCA1/2, including PALB2 and RAD51 relatively. Our study provides suggestive evidence of the prognostic role of BRCA1/2 in breast cancer and the therapeutic target for breast cancer. Furthermore, BRCA1/2 may influence BRCA prognosis through catalytic activity, acting on DNA, chromosomal regions, organelle fission, and the cell cycle. Nevertheless, further validation is warranted.

THE EXPRESSION OF NFATC1 IS MORE PREDOMINANT IN TRIPLE NEGATIVE BREAST CARCINOMA PATIENTS

Breast carcinoma is the most common malignancy among women in developed and developing countries. Invasive breast carcinomas are classified into 4 subtypes i.e. luminal A and B, human epidermal growth factor receptor 2 (HER2)-enriched and triple negative, the latter has the worst prognosis. Nuclear factor of activated T cell (NFATc)1 is an important transcription factor in malignant transformation and progression. Therefore, NFATc1 expression may determine prognosis of breast carcinoma. This study aimed to determine the roles of NFATc1 inbreast carcinoma progression. Materials and Methods Fifty-two paraffin blocks were selected and prepared to assess NFATc1 expression by immunohistochemistry. These data were taken from medical records: i.e. molecular classification, patient age, tumor size, lymphovascular invasion and grade of tumor were recorded. Results: Positive NFATc1 expression was observed in 4 samples i.e. in the nuclei of luminal A (1 out of 12; 8.8%), luminal B (1 out of 15; 6.7%), and triple negative (2 out of 12; 16.7%), but no NFATc1 expression was detected in HER2-enriched samples. Clinicopathologically, more of these patients were in the fifth decade (38.5%), with larger tumor size (?2 cm; 90%), lymphovascular invasion positive (80.8%), and high degree (3; 59.6%). Conclusion: NFATc1 expression is more predominant in triple negative breast carcinoma.

Membrane tension sensing molecule-FNBP1 is a prognostic biomarker related to immune infiltration in BRCA, LUAD and STAD

BackgroundFormin-binding protein 1/17 (FNBP1/FBP17), as a membrane-bound protein, is wildly expressed in eukaryotic cells and performs a critical role in tumor tumorigenesis and progression. However, the relationship between FNBP1 and immune infiltrating cells, prognostic value in patients still require comprehensive understanding. We purposed to explore the correlations of FNBP1 expression, prognosis and immune infiltration levels in various cancers.MethodThe expression and survival data of FNBP1 were collected from Oncomine, TIMER, GEPIA, Kaplan–Meier Plotter and PrognoScan databases. Correlations between FNBP1 and immune infiltrates were analyzed in TIMER and GEPIA databases.ResultsCompared with normal tissues, FNBP1 is significantly differentially expressed in a variety of tumor tissues. FNBP1 has significant and complex effects on the prognosis of kinds of cancers. High-expression was obviously correlated with better prognosis in breast carcinoma and lung adenocarcinoma, while worse prognosis in stomach adenocarcinoma. Besides, FNBP1 had a correlation with various immune infiltrating cells and diverse immune gene markers in breast invasive carcinoma (BRCA), lung adenocarcinoma (LUAD), and stomach adenocarcinoma (STAD). FNBP1 was also positively correlated with the adjustment of CD8+ cells, T cells, M2 macrophage, neutrophils, monocyte, Th1 cells, T regulatory cells (Treg) and Tumor-associated macrophages (TAMs). The expression level of FNBP1 is closely positively correlated with the expression level of multiple immune checkpoints in the three cancers. In addition, FNBP1 is significantly positively correlated with the expression levels of a variety of immunosuppressive molecules.ConclusionOur findings reveal FNBP1 can serve as a significant biomarker to influence the prognosis and the immune infiltrating levels in different cancers. The differential expression of FNBP1 might not only contribute to the judgment of metastatic and non-metastatic tumors but also in the immune escape by upregulating the expression of immune checkpoints.

Vitamin D receptor (VDR) mRNA overexpression is associated with poor prognosis in breast carcinoma.

PurposeThe prognostic value of vitamin D receptor gene (VDR) expression in breast cancer development is unclear. Here, we aimed to investigate whether VDR expression can be used as a prognostic indicator of breast cancer.MethodsWe used various public bioinformatics platforms: Oncomine, GEPIA, UALCAN, Kaplan-Meier plotter, UCSC XENA, bc-GenExMiner, WebGestalt, and STRING database.ResultsWe found that VDR was upregulated in breast cancer in comparison to normal tissues. Overexpression of VDR was significantly associated with worse overall survival in breast cancer. The expression of VDR was related to age, TNM stages, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor 2 status, basal-like (PAM 50) status, triple-negative breast cancer (TNBC) status, and basal-like (PAM 50) & TNBC status (P < 0.05). Increased VDR expression in breast cancer was significantly associated with older age. The 5 hub genes for VDR were NCOA1, EP300, CREBBP, and RXRA.ConclusionOur investigation offers hints about the prognostic role of VDR in breast cancer. The findings suggest that VDR expression might be used as a marker to determine a breast cancer patient’s prognosis. Nevertheless, further validation is warranted.

A Case Report of Accessory Breast Cancer in the Anterior Chest Wall

We present and discuss a case report of a 70-year-old patient with a primary carcinoma in accessory breast tissue in the anterior chest wall. Accessory breast tissue has a reported incidence of 0.3% to 6% in the general population, resulting from an incomplete involution of the mammary milk line. It usually presents as a palpable mass. The most frequent localization of accessory breast tissue and its possible pathologies is the armpit, although it can occur in the inframammary region and rarely on thighs, perineum, groin, or vulva. The diagnosis is mainly clinical, but imaging findings may be helpful to confirm the suspicion because they are similar to breast cancer within the breast. Ultrasound is the most useful radiological method to evaluate these lesions and guide the suspected diagnosis together with the clinical presentation. Treatment should be performed under the same principles as breast cancer, both surgical and systemic therapies. The prognosis of accessory breast carcinoma may be poor in cases with delayed diagnosis compared to native breast cancer.

Role of MicroRNA-31 (miR-31) in Breast Carcinoma Diagnosis and Prognosis.

Breast cancer (BC) is among the most widespread malignant tumors in women. In the current study, we evaluated the role of miR-31 in BC patients and its relation to the different prognostic, clinical, and pathological features. MiR-31 levels were determined by RT-PCR in BC and adjacent normal breast tissues from 100 BC patients. BC diagnosis was established through histopathological examinations. The expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) receptor in all tumors was determined using immunohistochemistry. MiR-31 expression was reduced in BC tissues relative to adjacent healthy breast tissue (mean levels were 0.93 and 7.2, respectively). Also, the low expression of miR-31 in BC patients was significantly correlated with adverse clinical and pathological features such as: young patient's age, premenopausal status, infiltrative lobular carcinoma, ER and PR negative tumors, HER2 positive tumors, and advanced clinical stage. MiR-31 was expressed at low levels in BC tissues and correlated with adverse clinical and pathological features, and poor survival.

Clinicopathological Study of Breast Lesions with Special Reference to the Role of CD34 Immunostaining in DiagnosisA Cross-sectional Study from a Tertiary Care Hospital of West Bengal, India

Introduction: Breast carcinoma is the most common cancer among women and leading cause of mortality. Prognosis of breast carcinoma primarily depends on early detection. The changes in molecular and antigenic expression in stromal microenvironment surrounding the tumour cells was noted earlier in tumours of skin and gastrointestinal tract which showed loss of Cluster of Differentiation 34 (CD34) expression in stromal cell of malignant tumours. Aim: To evaluate the intensity of CD34 staining in benign, borderline and malignant lesions of breast and to find out whether it can help to differentiate benign and malignant lesions from borderline and in situ carcinomas. Materials and Methods: This was a cross-sectional prospective study done over a period of 18 months in a tertiary care hospital of Bankura, West Bengal, India. Total 78 specimens of breast lesions obtained by lumpectomy and Modified Radical Mastectomy (MRM) were first evaluated on routine histology and classified as benign, borderline or malignant accordingly. Subsequent immunohistochemical staining was performed for CD34 and intensity of expression in stromal cells was graded from 0 to 3+. Then comparison of CD34 expression in different lesions was done and level of significance was assessed by using Student’s t-test. Results: Out of total 78 cases evaluated, 50 (64.1%) were categorised as benign and rest 28 (35.9%) were either premalignant or malignant lesions. Intensity of CD34 expression was found to be significantly higher in benign and in situ lesions compared to malignant epithelial lesions of breast (p&lt;0.05) whereas those between borderline and malignant phyllodes found to be statistically non significant (p-value 0.342). Conclusion: CD34 immunostaining can help to differentiate benign and in situ carcinomas from invasive carcinomas, however its role in differentiating borderline from malignant phyllodes tumour is limited.

Sonographic Features of Pure Mucinous Brelast Carcinoma With Micropapillary Pattern.

ObjectivePrevious studies have mostly discussed the clinical manifestations and prognosis of mucinous breast carcinoma with a micropapillary pattern. The purposes of this study were to investigate the sonographic features of pure mucinous breast carcinoma with micropapillary pattern (MUMPC) and to identify the role of ultrasound in the differential diagnosis between MUMPC and conventional pure mucinous breast carcinoma (cPMBC).Materials and MethodsWe obtained written informed consent from all patients, and the Ethics Committee of West China Hospital approved this retrospective study. The study was conducted between May and August 2020. We enrolled 133 patients with 133 breast lesions confirmed as mucinous breast carcinoma (MBC) histopathologically between January 2014 and January 2020.We retrospectively assessed sonographic features (margin, shape, internal echogenicity, calcification, posterior acoustic feature, invasive growth, blood flow grade, and rate of missed diagnosis) and clinical characteristics (age, tumor size, tumor texture, initial symptom, and lymph node metastasis). Bivariable analyses were performed using SPSS version 19.0.ResultsThe 133 lesions included 11 MUMPCs, 65 cPMBCs, and 57 mixed MBCs (MMBCs). There were significant differences in margin, shape, calcification, posterior acoustic feature, invasive growth, rate of missed diagnosis, average tumor size, and lymph node metastasis among the three groups (p < 0.05). The subsequent pairwise comparisons showed that there were significant differences in lymph node metastasis, margin, and invasive growth between MUMPC and cPMBC (p < 0.05). In patients aged >45 years, there was a significant difference in tumor size among the three groups (p = 0.045), and paired comparison showed that the average tumor size in the cPMBC group was larger than that in the MMBC group (p = 0.014).ConclusionMUMPC showed a non-circumscribed margin and invasive growth more frequently than cPMBC did. Lymphatic metastasis was more likely to occur in MUMPC than cPMBC. Ultrasound is helpful to distinguish MUMPC from cPMBC.