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Objective: In the hypothalamic-pituitary-gonadotrophin axis, estrogen plays a key role in the regulation of bone maturation and growth plate closure. This study was designed to explore the link between single nucleotide polymorphisms (SNPs) in the estrogen receptor 1 (ESR1) gene with idiopathic short stature (ISS) susceptibility in a North Indian population. Methods: Four SNPs of ESR1 (rs543650, rs6557177, rs2234693 and rs9340799) were genotyped by Sanger sequencing in ISS patients and controls. Linkage disequilibrium (LD) and haplotyping were done by SNPStat and SHEsisPlus software. The extent of LD was determined by calculating D' and R2 values in SNP paired combinations. Results: Fifty-two ISS patients were compared with 68 controls. A significant positive association was found between rs6557177 and rs543650 genotype and ISS susceptibility. The frequencies of the rs6557177 CC genotype [p=0.030; odds ratio (OR)=0.13; 95% confidence interval (CI): 0.01-1.10] and rs543650 genotype TT (p=0.043; OR=0.29; 95% CI: 0.09-0.92) were increased in the ISS group compared with controls. However, no significant correlation was observed between clinical parameters of patients and these SNPs. rs543650 showed strong LD with rs2234693 and rs9340799, similarly rs2234693 and rs9340799. Conclusion: Our study showed that the CC genotype at rs6557177 and TT genotype at rs543650 of ESR1 constituted a risk factor for developing ISS in North Indian children. These findings may lead to a better understanding of the SNPs associated with ISS susceptibility. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is the most common gynaecological disorder among reproductive-age women. Impaired metabolism of androgens and estrogens is one of the leading causes of PCOS. In India, medicinal herbs are being explored for their anti-androgenic and anti-estrogenic properties. In this study, we have screened the seed extracts of the herbal plant, Caesalpinia bonducella for potent inhibitors of estrogen and testosterone biosynthesis and assimilation. Methanol extract of C. bonducella seed kernels were subjected to gas chromatography - mass spectrometry (GC-MS) to identify the phytochemical constituents. Out of forty-three phytochemical compounds identified from the extract, eight compounds were selected based on Lipinski's rule of five for molecular docking. The selected phytochemical compounds were docked against specific targets of ovarian steroidogenesis pathway; human aromatase (CYP19A1), human 17β-hydroxysteroid dehydrogenase type 1 (HSD17B1), human androgen receptor and estrogen receptor α. Further, the nature of these compounds was validated using density functional theory (DFT) calculations and ADME/T studies. As per the molecular docking output, compounds 33, 35, 38, 40, and 43 exhibited higher binding affinities against the four selected targets. Phytochemical compounds were optimized using Gaussian 16 with the B3LYP function and the 6-31G(d, p) basis set and were correlated with docking results. ADME/T helps in identifying the potential drug candidates from a pool of drugs. Five phytochemical compounds, 33, 35, 38, 40, and 43 were found to have the ability to bind and inhibit appropriate targets in the ovarian steroidogenesis pathway. Hence, these compounds can be further characterized in vitro and in vivo for alleviating PCOS. [ABSTRACT FROM AUTHOR]

In India, breast cancer is the most common cause of mortality for women and has the potential to spread to other body organs. As a transcription factor, interactions with the estrogen receptor (ER) alpha are primarily responsible for the development of malignant tumors. Aromatase inhibitors are the most often used treatment for ER(+) breast cancer. Various synthetic compounds have been developed over the years to block the aromatase receptor, however, the majority of them are hazardous and cause multidrug resistance. So, combating these natural drugs can be prioritized. The current study was conducted to investigate the anticancer potential of Lagenaria siceraria phytoconstituents against breast cancer target protein (PDB ID: 3EQM) based on a literature review. In this study, 34 Lagenaria siceraria ligands were chosen, and the structure of the human aromatase receptor was acquired from the protein data bank. For those natural chemicals, molecular docking, drug-likeness, toxicity, and molecular dynamics were used to evaluate and analyse their anti-breast cancer activity. Five substances, 2,3-Diphenyl quinoxaline, 17–Acetoxy pregnolone, Benzyl–d-glucoside, Ergostenol acetate, and Stigmast-7-en-3-ol, shown higher binding affinity than Tamoxifen, signaling their potential use in breast cancer treatment. [ABSTRACT FROM AUTHOR]

Background: Oral lichen planus (OLP) is an autoimmune disease primarily affecting the middle-aged females. The present study aims to determine the relation of the oestrogen receptor alpha (ERα) with OLP pathogenesis, correlating it with the possible cause of its higher prevalence among females. Materials and Methods: Clinically and histologically identified fifteen of each pre-menopausal and peri-menopausal OLP female patients were chosen for this study. The expression of ERα was analysed from the collected lesion tissue samples by using two-step semi-quantitative reverse transcriptase polymerase chain reaction (SqRT-PCR) and enzyme-linked immunosorbent assay (ELISA). Results: mRNA and protein expression of ERα were significantly higher in both groups of OLP female patients when compared with the control. The perimenopausal OLP patients showed significantly elevated expression of ERα compared to premenopausal patients. Conclusion: Higher expression of ERα in pre- and peri-menopausal females may be a causative factor for the higher prevalence of OLP among females. [ABSTRACT FROM AUTHOR]

The fibroadenoma is considered as a manifestation of aberration in normal development and involution (ANDI); however, its exact etiopathogenesis is poorly understood. We investigated the role of oestrogen (ER) and progesterone receptors (PR) in Fibroadenoma, to assess the ER and PR expression in epithelium and stroma of fibroadenoma and to co-relate this expression with the response to centchroman therapy. Fifty ladies with 65 fibroadenomas were investigated. Tissue from core biopsy of lesions was stained for estimating the ER and PR expression in the epithelial cells and in stroma. Patients received tablet centchroman 30 mg daily for 3 months, and the response to therapy was evaluated. A regression ≥ 30% in largest dimension of fibroadenoma on sonography was considered a significant response. The association between the response and ER and PR expression in epithelium and stroma was assessed. In the epithelium: ER positivity = 62.5%; PR positivity = 93.75%. In the stroma, the ER positivity = 2% and PR positivity = 8.3%. Response to centchroman was observed in 33/48 = 68.7%. Among the 33 responders, 23 lesions expressed ER in epithelium, while 10 lesions were ER negative. The relative risk of regression with "ER positivity of epithelium" as exposure = 1.38 (95% CI; 1.35–1.40, p = 0.12). Among responders, 30/33 exhibited PR positivity in epithelium. Expression of ER and PR in the epithelium of fibroadenoma is associated with significant regression in size with 3 months of therapy with centchroman. [ABSTRACT FROM AUTHOR]

Unlike in the west, breast cancer in India presents more than a decade earlier, predominantly in stage III, and with an unusually large percentage of poor-prognosis triple-negative subtype. Vitamin D deficiency prevails in epidemic proportions in India. Cross-sectional observational study to correlate serum vitamin D levels with molecular subtypes of breast cancer. In fifty breast cancer patients, core needle biopsy was used for receptor status and molecular subtyping. Serum vitamin D was documented prior to treatment. Serum vitamin D levels were correlated with molecular subtypes of breast cancer. The mean age was 45.68 years. None were in stage 1, while 48% were in stages 2 and 3 each. On biopsy, 90% were ductal carcinoma. The largest group of patients was triple negative (34%). In triple-negative subtype, majority (71%) were stage 3. Fifty percent of stage 3 patients were triple-negative subtype. The mean serum vitamin D levels were 15.78 SD 7.34 ng/ml. The lowest mean serum vitamin D levels were seen in triple-negative subtype, i.e., 11.49 SD 4.17. The difference was statistically significant among the subtypes. Vitamin D deficiency (present in 96% of our patients) has a significant association with triple-negative breast cancer (associated with worst prognosis), as compared to other molecular subtypes, suggesting vitamin D deficiency to be a likely significant risk factor for the development of breast cancer, particularly triple-negative subtype which is present in unusually large proportion in India. Identification of vitamin D deficiency as an important (and easily modifiable) risk factor for breast cancer could help define effective preventive strategies. [ABSTRACT FROM AUTHOR]

Introduction: Breast carcinomas have shown increasing incidence across the world over the recent few years. The different epithelial cells play a role in the pathogenesis of different breast lesions consistent with the varying cytokeratin (CK) expression profiles. The luminal cells express CK 8 and 18 while myoepithelial cells show CK 5/6 and CK 17 expression. Triple Negative Breast Cancers (TNBC) (hormonal receptors and Human Epidermal growth factor Receptor 2 (HER2)/neu negative) express basal cytokeratins and histopathologically show metaplastic to medullary features while luminal breast cancers with glandular differentiation show hormonal receptor or HER2 expression. Also basal cells are characteristic of benign lesions like epithelial hyperplasia, fibroadenoma etc while being absent in atypical hyperplasia and preinvasive lesions. Aim: To study cytokeratin 5/6 and Estrogen Receptor/Progesterone Receptor (ER/PR) expression pattern in proliferative, preinvasive and malignant lesions of breast. Materials and Methods: An observational cross-sectional study was undertaken in the Department of Pathology in a tertiary care hospital in East India, from January 2019 to June 2020. A total of 41 samples diagnosed as proliferative (Usual Ductal Hyperplasia (UDH)/Atypical Ductal Hyperplasia (ADH), preinvasive Ductal carcinoma in Situ (DCIS) and invasive breast carcinomas were selected by systematic random sampling. Immunohistochemical examination was done using monoclonal antibodies against Cytokeratin 5/6 and ER/PR/HER2 after obtaining thin sections from formalin fixed paraffin embedded blocks and retrieval of antigen. The data was interpreted by light microscopy using a semi-quantitative method with respect to prefixed parameters and statistical analysis was done by Chi-square test and Fisher’s exact test using Statistical Package for the Social Science (SPSS) version 25.0. Results: Of the 41 case three were of proliferative lesions (UDH+ADH), one of the case (UDH) constituting 33.3% of total showed positive CK 5/6 expression and two of the cases (ADH) mounting to 66.7% of total showed negative CK 5/6 expression. Of two preinvasive lesions (DCIS), 100% of them showed negative CK 5/6 expression. On categorisation of carcinoma cases into molecular subgroups as indicated by surrogate immunohistochemical expression, it was found that majority of the cases (20) exhibited Luminal-A Like molecular profile constituting 55.6% of total. This was followed by an equal incidence of HER2/neu enriched (non luminal) and triple negative phenotypes, both being five in number, individually constituting 13.9%. Both Luminal B-like (HER2-positive) and Luminal B-like (HER2-negative) were three in number contributing to 8.3% of total each. Out of 36 malignant cases, five of them showed positive CK 5/6 expression constituting 13.9% of the total while rest of them showed (31) negative CK 5/6 expression constituting 86.1% of total. All these five cases showing positive CK 5/6 expression belonged to triple negative molecular subtype and this association between the molecular subtypes and CK 5/6 expression pattern was statistically significant as the p-value was 0.0034 (<0.05). Of total five TNBC cases, two of the cases (40%) were reported to have weak positive CK 5/6 immunostaining, while three (60%) of the cases had moderate intensity. Still none of these cases exhibited strong immunostaining. The single UDH case reported in present study, exhibited strong positive immunostaining with CK 5/6. Conclusion: The proliferative lesions consisting of both luminal and myoepithelial cells like UDH showed strong membranous and cytoplasmic expression while ADH, DCIS, and invasive breast carcinoma comprising primarily of luminal epithelial cells were negative for basal cytokeratin 5/6 expression. These group of breast carcinomas belonged to other immunophenotype categories apart from TNBC. However, a special immunophenotype TNBC group, negative for ER/PR and HER2/neu was strikingly positive for CK 5/6 and a statistically significant association was found. [ABSTRACT FROM AUTHOR]

Background & Objective: Breast cancer is the leading cancer among Indian women and accounts for about 25% of all cancer cases worldwide. The present study aimed to assess Programmed Death Ligand-1 (PD-L1) expression in tumoral cells and tumor-infiltrating lymphocytes (TILs) and evaluate their correlations with the Ki-67 labelling index in invasive breast carcinomas (IBC). Methods: This descriptive observational study was conducted during 2016-2018 and included all diagnosed cases of IBC. The relationships between PD-L1 expression, TILs, hormone receptors, Ki-67, and clinicopathological parameters were studied in IBC. Statistical analysis was performed by SPSS version 23. Results: Out of 114 evaluated cases, 33.33% (N=38) showed PD-L1+ expression in tumor cells and 47.37% (N=54) had PD-L1+ expression in TILs. A high Ki-67 index was observed in 96 cases. Moreover, 49 patients were estrogen receptor (ER)- and 65 were ER+. We observed that 22 of 49 ER- and 49 of 65 ER+ subjects showed PD-L1+ expression, respectively. Conclusion: Our results showed a significant relationship between PD-L1 expression in tumoral cells and TILs, as well as between Ki-67 and TILs. In addition, an inverse correlation was noted between PD-L1 expression and ER. The PD-L1 expression in tumors and TILs and correlation with high Ki-67 may prove the importance of PD-L1 in targeted chemotherapy. An inverse relationship between PD-L1 and ER expression in tumoral cells suggests scope for immunotherapy in ER- IBC. However, further research with more cases is required. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the most common cancer in female representing approximately 25% of all cancer. It is also ranked number one cancer among Indian females with age adjusted incidence rate of 25.8 per 100,000 women and mortality 12.7 per 100,000 women. Hormone receptors are the receptor protein found in normal breast cells. Aims and Objectives: The aims of this study were to assess the histologic type, estrogen receptor (ER), progesterone receptor (PR), and HER2/neu of all breast carcinoma patients coming to the inpatient department of general surgery of a tertiary care hospital. This study was conducted to assess the histologic type, ER, PR, and HER2/neu of all breast carcinoma patients coming to the outpatient department of general surgery of a tertiary care hospital. Materials and Methods: The present study is a prospective observational study conducted in the department of general surgery at KR Hospital for 1 year from December 2020 to November 2021. All patients who underwent modified radical mastectomy for breast carcinoma or core biopsy to start chemotherapy and hormone therapy before surgery were included in the study. They were subjected to histopathological examination and immunochemistry. Results: The most common age group, in which breast carcinoma was diagnosed, was 51–55 years. The most common type of breast carcinoma is invasive ductal carcinoma seen in 66% of the patients. Among the 100 patients IHC, ER positive was seen in 54% of the patients, PR positive was seen in 39% of the patients, and HER2neu-positive was seen in 31% of the patients. Most common was ER/PR+HER2neu – in 28% of the patients. Triple-negative hormonal status was seen in 23% of the patients. Conclusion: This single institutional study of 100 cases of breast cancer patients from South India suggest that mean age of breast cancer patient was between 51 and 55 years, with invasive ductal carcinoma being the most common histological type with ER positivity of 54% and PR positivity of 39% and triple-negative cancers of 23%, not grossly different from rest of the country but significantly lower than Western studies. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Invasive Breast carcinoma--No special type (NST) is the most common breast malignancy accounting for 95% of breast cancers. Study of predictive and prognostic immunohistochemical markers estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (Her2neu) expression are crucial for treatment planning. MATERIALS AND METHODS: IN the present study we studied the hormonal profile in 303 sporadic breast cancers and BRCA1 protein expression in these patients along with its clinico-pathological correlation. RESULTS: In our patient population, Triple negative Breast carcinoma (TNBC) (104/303; 34.3%) was the most common luminal subtype followed by Luminal A 74/303; 24.4%), Her2 enriched (65/303; 21.5%), and Luminal B (60/303; 19.8%) respectively. This contrasts with many western studies which commonly report Luminal A being the largest subgroup. BRCA1 protein loss was more prominently seen in TNBC (64/104;61.5%) highlighting the possibility that high grade tumors are more susceptible to some epigenetic modifications leading to higher likelihood of loss of BRCA1 protein. CONCLUSION: Hence, we conclude that like hereditary cases of breast carcinoma with BRCA1 mutation; BRCA1 loss is also more likely in sporadic TNBC cases. [ABSTRACT FROM AUTHOR]

Introduction: Male breast cancer (MBC) accounts for around 1% of all breast cancers. However, the incidence & patterns of MBC varies in different parts of the world. Due to the rarity of its occurrence, very few literature are available regarding its peculiarities. Material & Methods: A total of 119 patients of MBC were included in this retrospective analysis, who were registered in a single regional cancer center in India over 30 years period from 1991 to 2020. Data from all patients were collected to evaluate the spectrum and patterns of MBC concerning presentation, distribution, and clinicopathological characteristics. Results: Total of 119-patients of MBC were registered in this time. The median age of presentation was 59 years. The right to left ratio was 1.25:1, which indicated that both sides breast was equally affected. Most of the patients (68.1%) presented late in the disease course with locally advanced or metastatic lesions. The majority of breast lesion was central or retro-areolar in location and infiltrating ductal carcinoma histology was found in more than 90% of patients. Estrogen and progesterone receptor positivity was seen in 42.9% and 29.4% of patients, respectively. The most common metastatic site was bone. Conclusion: Our data regarding MBC patients matched closely with existing literature. However, it is seen MBC patients presented to oncologists in a locally advanced stages; either because of shyness or unaddressed health education. Emphasis should be given to prospective studies to gather more knowledge about the demography and pattern of this rare yet sprouting malignancy. [ABSTRACT FROM AUTHOR]

Introduction: Rapid histopathological processing of neoplastic biopsies is crucial for initiating early therapy in patients. Microwave processing shortens the time to diagnosis and is less labour intensive. Aim: To compare the quality of immunohistochemical staining of Estrogen Receptors (ER) and Progesterone Receptors (PR) on paired breast samples using microwave processing versus conventional processing. Materials and Methods: A cross-sectional study was conducted at a tertiary care hospital in Kerala, India, from February 2014 to September 2015. A total of 44 paired samples from breast carcinoma patients were taken. Baseline characteristics of the patients such as age and type of carcinoma were noted. Haematoxylin and Eosin (H&E) stain was used. One slide of the pair was processed conventionally and the other using a microwave. The stained slides were observed by three pathologists. The validity of ER and PR receptor status was evaluated with sensitivity, specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV). Kappa statistics and spearman’s correlation test was used to denote the agreement between them. Results: The mean age was 51.32±11.16 years. There was agreement (Cohen k= 0.902) between the microwave processed and conventionally processed paired breast samples for ER. The sensitivity and specificity of microwave processing in ER evaluation was 87.5% and 100% while that of PR evaluation was 92.9% and 100% respectively. The PPV was 100% and NPV was 93.3% for ER evaluation by microwave processing. Conclusion: Microwave aided tissue processing had significant advantages over conventional methods for providing a rapid diagnosis, being less laborious and had effective staining, which makes it a better choice. [ABSTRACT FROM AUTHOR]

Background: Breast carcinoma is the most prevalent malignancy in females globally and also the leading cause of cancer-related mortality. The immunohisto- chemistry (IHC)-based molecular subtyping has put newer insights into the biological behaviour and clinical management of breast carcinoma. We conducted the present study to correlate the four IHC-based molecular subtypes: Luminal A, Luminal B, Human epidermal growth factor receptor 2 positive, and triple negative breast carcinoma with various clinicopathological parameters amongst the industrial population of Haryana. Method: This cross-sectional study was conducted on 92 cases of invasive breast carcinoma, who underwent modified radical mastectomy over a period of 2.5 years with the prior approval of Institutional Ethical Committee at ESIC Medical College and Hospital, Faridabad. We performed routine histopathological examination along with IHC (Estrogen receptor, Progesterone receptor and Human epidermal growth factor receptor 2) study. The correlation of the four molecular subtypes with various clinicopathological parameters were also studied. We analysed the data using SPSS software. Results: The mean age of the patients in this study was 47 years with a maximum number of cases in the 3rd and 4th decade of their life. The most common subtype was luminal B (40.9%) with the maximum number of cases presenting in stage II (53.26%) and with grade II (51.1%). Triple-negative breast cancer was found to be associated with brisk mitosis, lymphovascular invasion (66.67%), necrosis (77.78%), and ductal carcinoma in situ (66.67%). These findings were clinically significant. (P<0.05) Conclusion: The early age of presentation of breast carcinoma in the industrial population would warrant the need to focus on various molecular subtypes and clini- copathological parameters that may have different prognostic implications in this population. [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer is commonly diagnosed cancer in women. Tumor receptors estrogen receptor (ER) and progesterone receptor (PR) are well recognized prognostic factors for breast cancer. Materials and Method: Data from the department of pathology for the 5-year period (2010 to 2014) is used for analysis for Kamrup district of Assam, India. Kaplan Meir method was used to evaluate survival rate. Result: The overall 5-year survival is observed as 54.6%. There is a 10.6% improvement in survival was recorded among those who living in the urban areas. The risk of death was 40% higher for those who were resides in rural areas compared to urban areas (P = 0.070). There is a 6 fold variation in survival was observed according to their stage at presentation. Hormone receptors found to be play an important role in survival outcome. Patients with ER/PR+ (positive) status have 13.6% higher survival rate than those with ER/PR-. The overall survival for ER/PR positive is 72.1% compared to 58.5% of ER/PR negative. Conclusion: From the study it is observed that population with positive hormone receptors (ER/PR +) and living in the urban areas is experiencing survival rate. [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer is a heterogeneous disease that may differ in therapeutic response and prognosis despite similarities in histopathologic types, grade and stage. Molecular studies have identified distinct subtypes of breast carcinoma each having unique recognisable phenotypes and clinical outcomes. Aim: To study the histomorphological features and Immunohistochemical (IHC) profile of breast cancer, to study the distribution of molecular subclass, and to study the morphological features of different molecular subclasses and the association between the pathological features associated with adverse prognosis with the molecular subclass. Materials and Methods: Present study was a prospective crosssectional observational study based on mastectomy specimens of 122 cases of consecutive cases of invasive breast cancer submitted over 1.71 years in Department of Pathology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India. On IHC staining with Estrogen Receptors (ER), Progesterone Receptors (PR), Human Epidermal growth factor Receptor 2 (HER2), Cytokeratin (CK5/6) and Epidermal Growth Factor Receptor (EGFR) these cases were classified into Luminal A, Luminal B, HER2 overexpression, basal like and normal breast like molecular subclass. All statistical analysis were performed using Statistical Package for the Social Sciences (SPSS) version 16 (SPSS, Inc., Chicago, IL, USA). Results: The proportion of each subytpes detected in present study were: Luminal A-28.69% (35), Luminal B-17.21% (21), HER2 over expressing-25.41% (31), Basal-Like Breast Carcinoma (BLBC)-26.23% (32) and the rest unclassified category (normal breast like)-2.46% (3). The following variables were significantly associated with molecular breast cancer subtypes. The tumours of BLBC and Her2 overexpressing were larger, poorly differentiated, higher mitotic index, more number of positive lymph nodes and with more geographic and central necrosis than Luminal A group. These features were statistically significant (p<0.05). Conclusion: Identification of molecular subtype of breast cancer is extremely important for predicting prognosis and therapeutic response of the breast cancers and thus has role in management of patients of breast cancers. BLBC is a molecular subtype of breast cancer known for its aggressive behaviour and poor prognosis is identified by expression of basal CKs. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer is the fourth most common cancer in the world and the second leading cause of mortality in India atier breast cancer. Human papilloma virus (HPV) infection has been regarded as a key risk factor in cervical cancer, however it is not sufficient in the causation of the disease. Role of other cofactors like steroids and their receptors in the pathogenesis of carcinoma cervix is being studied extensively. Various in-vitro and some human studies have postulated a role of estrogen receptors in carcinoma cervix. Estrogen receptors (ER) were categorized into two subgroups (alpha and beta) atier the discovery of estrogen receptor beta in the mid-nineties. Studies show that ER alpha (ERa) and beta (ERß) have their own unique cell specific expression patierns and actions and may also have mutual antagonistic roles if present in the same tissue. Aim and Objectives: The aim of the research was to study and compare the expression of ER alpha and beta in ectocervix of healthy women and cervical cancer patients. Materials and Methods: One gram of cervical tissue was taken from 30 cervical cancer patients and 20 healthy women and subjected to immune histochemical analysis. The expression patiern of ER alpha and beta was studied in terms of number of women expressing the receptor and immunoreactivity scores and compared between healthy and cancerous cervix. Results: Ectocervical cells of both normal and cancerous cervix expressed both ER alpha (ERa) and beta (ERß) in their nuclei and only ER beta in their cytoplasm. Ninety percent of healthy women expressed ER alpha in the ectocervix compared to only 6.67% of cervical cancer patients (p=0.000). The mean immunoreactivity scores for ER alpha expression was also lower in cervical cancer patients (0.167±0.75) compared to healthy women (2.60±2.01) [p=0.000]. Conclusion: ER alpha and beta have different expression patierns in ectocervical cells. ER alpha is significantly down expressed while ER beta expression is retained or slightly increased in cervical cancer cells when compared to normal cervix. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BCA) is the second most common cancer among women in India and accounts for 7% of global burden of BCA. The axillary lymph node status is an independent prognostic factor. The combined estrogen receptor (ER), progesterone receptor (PR), and HER2/neu biomarker expression is a predictor of BCA status for therapeutic guidance. Studies have demonstrated that these biomarkers are unstable throughout their tumor progression. Varying concordance and discordance rates in the biomarker expression between primary breast carcinoma (PBC) and metastatic axillary lymph node (MALN) status are reported.Aim: This study was conducted for studying and comparing the expression of immunohistochemistry (IHC) markers, i.e., ER, PR, HER2/neu, p53, and Ki67 between PBC and their corresponding MALN for prognostication and therapeutic purpose.Methods: Sixty cases of PBC with metastasis to axillary lymph nodes diagnosed between years 2008 and 2014 were included in the study. A technique of manual tissue array was employed for cases subjected to IHC. Analyses of the expression of IHC markers were attempted between the PBC and their corresponding synchronous MALN and classified as concordant or discordant. Results were subjected to statistical analysis.Results: Substantial agreement was observed for biomarker ER, PR, HER2/neu, p53, and Ki67 expression between PBC and MALN with k-value 0.79, 0.75, 0.89, 0.7, and 0.6, respectively.Conclusion: There was high concordance for the IHC markers: ER, PR, HER2/neu, p53, and Ki67 expression in matched pairs of PBC and corresponding synchronous MALN. However, the discordance noted in small subgroups cannot be overlooked. Thus, there is a need to perform ER, PR, HER2/neu, p53, and Ki67 IHC studies routinely in both PBC and MALN to help design therapies that are tailored to target the specific tumor clones and render maximum benefit to patients. [ABSTRACT FROM AUTHOR]

Murraya koenigii (MK), a member of the Rutaceae family and widely known as the curry-leaf tree, is indigenous to India, Sri Lanka, and other south Asian nations. It is a renowned medicinal herb because of the wide range of bioactive components found in its leaves, such as girinimbine, koenimbine, mahanimbine and mahanine among others. All these bioactive components make this plant beneficial for treating a variety of ailments and diseases. Biological and pharmacological activities of MK include anti-oxidant, anti-microbial, anti-ulcer, anti-helminthic, anti-malarial, anti-trichomonal, hepatoprotective, anti-diabetic, etc. The present study aimed to evaluate the possible protective effect of hydroethanolic Murraya koenigii leaves extract (HEMKLE) against 7,12-Dimethylbenz[a]anthracene (DMBA)-induced breast cancer in rats, which further paves the way for future breast cancer treatment. For the preparation of hydroethanolic Murraya koenigii leaves extract (HEMKLE), Murraya koenigii (MK) leaves were taken from the botanical garden of the Panjab University campus, Chandigarh, and authenticated from the Department of Botany, Panjab University (accession number 22417). The phytochemical characterization of HEMKLE was performed using liquid chromatography–mass spectrometry (LC-MS). Following this, an in-silico molecular docking analysis was performed using Maestro Schrodinger software, and an in-vivo study was conducted. For the in-vivo study, female SD rats were divided into four different groups. Group I (C), Group II (DMBA), Group III (HEMKLE), and Group IV (HEMKLE + DMBA). Histopathogy, oxidative and antioxidant status, immunohistochemistry of estrogen receptor-α, TUNEL assays, mRNA and protein expression of apoptotic pathway genes were conducted in in-vivo study. In LC-MS, major phytochemical constituents including flavonoids and carbazole alkaloids were identified. In-silico docking study revealed the strong binding affinity between the identified compounds with caspase-3. Additionally, koenine displayed the highest binding affinity/minimum energy of −9.21 kcal/mol with 6BDV as compared to other phytochemicals. Furthermore, in-vivo experimentation revealed that HEMKLE administration in Group IV(HEMKLE + DMBA) significantly inhibits the tumor incidence and volume as compared to alone DMBA treated group. The antioxidant action of HEMKLE was proven from the in-vivo analysis of antioxidant marker enzymes, histopathology, immunohistochemistry of ER-α studies. Further, increase number of TUNEL positive cells was observed in co-treated animals as compared to alone DMBA treated animals. In Group IV (HEMKLE + DMBA), upregulated expression of pro-apoptotic genes and downregulated expression of anti-apoptotic gene were observed when compared to Group II(DMBA) suggested the apoptotic effect of HEMKLE. The results of the present study provide clear evidence of the chemopreventive capabilities of HEMKLE in rats with DMBA-induced breast cancer. The observed outcomes could potentially be attributed to the existence of diverse phytochemicals within the HEMKLE. [Display omitted] • GC-MS analysis of HEMKLE revealed the presence of alkaloids and flavonoids. • In silico analysis showed strong Caspase-3 binding with alkaloids and flavonoids. • HEMKLE reduces DMBA-induced breast tumors, oxidative stress, and estrogen hormone. • In vivo study revealed the apoptotic potential of HEMKLE against breast cancer. [ABSTRACT FROM AUTHOR]

Estrogen regulates bone homeostasis and has a cardio-protective effect. Its physiological functions are mediated through receptors (ER) whose expression can be regulated by presence or absence of polymorphisms. However, the association between ER polymorphisms and BMD as well as lipids are inconsistent. The aim of the study was to investigate whether polymorphisms in ESR are associated with bone mineral density (BMD) and lipids in a cohort of Indian women. We studied Pvu II, Xba I polymorphisms in ESR 1 and Alu I, Rsa I polymorphisms in ESR 2 genes and their association with bone mineral density (BMD) and lipids in premenopausal (n = 293, mean age: 33.01 ± 5.23 years) and postmenopausal (n = 145, mean age: 56.91 ± 7.1 years) women from Northeast India. Alu I and Rsa I polymorphisms in ESR2 gene were associated with BMD in postmenopausal women. Logistic regression analysis adjusted for age, BMI, tobacco and alcohol consumption revealed that xx genotype in Xba I polymorphism is associated with osteopenia at spine (OR = 3.3, 95% CI = 1.067–10.204) in postmenopausal women suggesting that allele X is protective (OR = 0.419, 95% CI = 0.177–0.991). Genotype aa in Alu I polymorphism, seemed to be protective (OR = 0.092 for osteopenia; OR = 0.152 for osteoporosis) at spine whereas A allele was associated with osteopenia at femur (OR = 2.123, 95% CI = 1.079–4.166) in postmenopausal women. Allele r of Rsa I polymorphism, was associated with osteoporosis at spine (OR = 3.222, 95% CI = 1.302–7.96). Thus, AIu I polymorphism of ESR 2 gene was associated with spinal and femoral BMD whereas Rsa I only with spinal BMD in postmenopausal women and ESR genotypes were not associated with lipids. • First Indian study reporting association of ESR2 polymorphism with bone density • AIu I polymorphism (ESR 2 gene) was associated with spinal and femoral BMD whereas Rsa I with spinal BMD in postmenopausal women • ESR polymorphisms were not associated with lipids [ABSTRACT FROM AUTHOR]

Background: Caesalpinia pulcherrima belonging to the family Fabaceae is used in India as a traditional medicine for a variety of ailments. Globally, traditional medicines are presently being used for the treatment of cancer. Objective: The present study was aimed at investigating the chemomodulatory potential of C. pulcherrima flowers in breast cancer and explaining its possible mechanism. Materials and Methods: The cytotoxic potential of ethyl acetate fraction of C. pulcherrima (EAFCP) flower was tested in MCF-12A (normal breast), MCF-7 (estrogen receptor [ER] positive), and MDA-MB-453 (human epidermal growth factor receptor 2 positive) human breast cancer cells by sulforhodamine B assay. Chemomodulatory potential was evaluated in vivo against N-methyl-N-nitrosourea (MNU)-induced mammary carcinoma in female Sprague Dawley® rats. The mechanism for anticancer potential was screened by in vitro studies involving Annexin V-FITC assay (apoptosis), cell cycle patterns, intracellular reactive oxygen species, and mitochondrial membrane potential measurement (FACS based) followed by docking study on estrogen receptor-alpha (ER-α). Results: The fractions showed perceptible cell growth inhibition potency (IC50< 50 μg/ml) in MCF-7 breast cancer cells. In MNU-treated animals, antioxidant enzymes and histological examination showed statistically significant (P < 0.001) changes. Treatment of MCF-7 cells with EAFCP reduced cell growth rate by a mechanism associated with both apoptotic and necrotic cell death. Molecular docking study further showed that rutin and catechin have a comparable binding affinity for the ER-α. Conclusion: In this study, we confirmed that EAFCP was most effective in reducing cell viability, scavenging physiological oxidant species, and causing mitochondria-mediated apoptosis and necroptosis in MCF-7 cell by selectively modulating the functions of ER-α. [ABSTRACT FROM AUTHOR]

PURPOSE: Biomarker—estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2/ neu) —discordance plays an essential role in the management and prognosis of patients with metastatic breast cancer. Rates of discordance have been previously reported around 12% to 35%, 30% to 50%, and 5% to 15%, respectively, in Western literature. Data are sparse regarding the same from developing countries, such as India. METHODS: We performed an ambispective review of paired biomarker status in patients with breast cancer—stage I, II, and III as per American Joint Committee on Cancer, 7th edition—who developed metastasis at recurrence (N = 103 patients). Biomarker status and clinical and radiologic parameters were documented at baseline and subsequent follow-up. RESULTS: Discordance was present in 21.3% for ER, 29.1% for PR, and 15.5% for HER2/ neu receptor. In our cohort, 7.8% had positive to negative ER and 13.6% negative to positive. Whereas 21.4% had positive to negative PR, 7.8% had negative to positive PR. Approximately 6.8% had positive to negative HER2/ neu receptor and 8.7% negative to positive. In our cohort, 41 patients (40%) had single-site metastasis—bone, 15.5%; lung, 11.7%; nonregional lymph node, 7.8%; liver, 3.9%; and brain, 0.97%. More than one site of metastasis was present in 62 patients (60%). The most common sites of metastasis were visceral—lung and liver—followed by bone, nonregional lymph node, skin, and brain. CONCLUSION: The current study demonstrated that metastatic disease evolution in breast cancer is characterized by change in the tumor biology, which leads to discordance in receptor status. Repeat biomarker studies at metastatic recurrence is warranted, especially if treatment plans include hormone and targeted therapy. [ABSTRACT FROM AUTHOR]

Aim: Routine assessment of cell proliferation is recommended in the pathologic evaluation for all breast cancers. Considering the poor reproducibility and interobserver variability in mitotic counts, Ki-67 is an easily available and reliable substitute for mitotic counts and has been shown to have a significant relationship with the histologic grade of malignancy and the mitotic activity of tumors. Our study aimed at exploring Ki-67 expression and studying its correlation with other established prognostic parameters.Materials and Methods: Seventy-five cases of primary breast cancer undergoing radical or modified radical mastectomy constituted the study group. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2)/neu, and Ki-67 was assessed in each case. Ki-67 labeling index (Ki-67-LI) was estimated as the number of positive nuclei divided by total number of nuclei scanned counting a minimum of 1000 cells in 10 selected high power fields that displayed the highest immunoreactivity and was expressed as percentage. Ki-67 expression was correlated with various clinicopathologic prognostic parameters including age, tumor size, tumor type, axillary lymph node status, and histologic tumor grade.Results: A statistically significant direct association was observed between Ki-67-LI and tumor size, histologic grade and Nottingham prognostic index. A statistically significant inverse association was observed between Ki-67-LI and ER and PR expression. However, no association was observed between Ki-67-LI and menopausal status, lymph node involvement and HER2/neu expression.Conclusion: Based on our results, we concluded that modified Bloom-Richardson (MBR) grading has been recognized as a treatment related indicator. The accuracy and reliability in grading have always been a matter of concern, hence, the reproducibility of grading should be enhanced. Ki-67-a proliferation marker is easily identified and provides comparable accurate information. In contrast to poor reproducibility of mitotic counts, Ki-67 can achieve high agreement between pathologists; is more reproducible; adds complementary value to the MBR grading system and correlates well with other clinicopathologic parameters. It may act as a significant prognostic indicator for routine clinical use and be helpful for selection of adjuvant treatment. It can also add value in categorizing Grade II tumors into two prognostic subgroups with prognosis equivalent to Grades I and III, respectively. [ABSTRACT FROM AUTHOR]

Background: In India, carcinoma breast is the most common cancer among urban women population and second most common cancer after carcinoma cervix in rural areas. One in 22 women in India develops carcinoma of the breast in their lifetime. Fluorine-18-fluoro-2-deoxy-D-glucose (18F-FDG) uptake in breast cancer usually indicates the degree of tumor metabolism and hence can predict its behavior and prognosis. On the other hand, the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2) or neu state of breast cancer is a biomarker that provides important prognostic information in addition to predicting response to therapy.Aims: The main objective of this study is to assess whether a correlation exists between 18F-FDG uptake in untreated cases of breast cancer, their receptor status (ER, PR, and HER-2 or neu), tumor histology, and tumor size.Subjects and Methods: Sixty consecutive female patients, with biopsy-proven primary breast cancer, were enrolled in this prospective study for whom 18F-FDG positron emission tomography-computed tomography scan was done in the Department of Nuclear Medicine. Results obtained were analyzed using appropriate statistical tests (t-test and Pearson Chi-square tests), and interpretation was made with 95% confidence level.Results: In our series, a positive correlation between tumor size, high tumor grade, and standardized uptake value (SUV) was found. Tumors with positive receptor status for estrogen, progesterone, and HER-2/neu receptors had statistically insignificant lower maximum SUV (SUVmax) values than their negative counterparts. Triple-negative breast tumors (ER-, PR-, and no overexpression of HER-2/neu) are currently a subject of major interest because of their aggressiveness, poor prognosis, and lack of targeted therapy. Based on receptor status when the SUVmaxof the group with triple-negative receptor status (ER-/PR-/HER-2/neu-) was compared to rest of the patient group, it was seen that patients with negative receptor status had significantly higher mean SUVmaxvalues.Conclusions: We have inferred that in patients with breast cancer, various biological parameters such as tumor size, grade, histology, and hormonal receptor status have different impact on tumor metabolic activity. [ABSTRACT FROM AUTHOR]

Background: Different molecular classes of breast cancer (BRCA) correlate with prognosis and response to therapy. Triple-negative breast cancer (TNBC) is a newer concept and very limited studies were carried out in India. The aim of this study was to profile the molecular types with a particular emphasis on TNBCs. Materials and Methods: Prospectively evaluated descriptive study for 2 years from June 2014 to March 2016, was carried out in the Department of Pathology and Surgery in a tertiary care institute. Cases included were of invasive breast carcinoma in females, confirmed by histopathology. Ethical clearance was received. Data were analyzed using Statistical SAS software. Results: A total of 123 cases of invasive BRCA were studied and mean age was 44.64 years. The peak age group was 36-45 years (43.9%). Tumor sizes =2 cm was 30%, between 2 and 5 cm was 50.40%, over 5 cm was 19.51%. Invasive duct carcinoma was 82.11% and invasive lobular carcinoma 8.13%. Only 21% of subjects presented as early breast carcinoma. Cases of 1-3 nodes were 22.8%, 4-5 nodes 21.1%, more than five nodes were 34%. Histologic Grade 3 was 50.4%, Grade 2 was 41%, and Grade 1 was only 8.1. The American Joint Committee on Cancer, Stage 1 (17.9%) in Stage 2 (29.3%) Stage 3 was 46.3%, Stage 4 was 6.5%. Estrogen receptor was in 40.62%, progesterone receptor 35.77%, Her2/Neu 18.69% luminal A (19.51%), luminal B (21.13%), Her2/Neu type (17.88%), and triple negatives (38.21). Conclusion: The present study showed significantly higher TNBC with poor prognostic factors in younger women in a background of peculiar ethic spectrum in this geographical region. [ABSTRACT FROM AUTHOR]

Abstract: Background: Stroke is a complex disease caused by combination of multiple risk factors. Recent findings have suggested that stroke has a strong genetic component. Evidence suggests that variations in the estrogen receptor α (ESR1) gene may influence stroke risk. Aims: The present study was carried out to investigate the role of ESR1 gene polymorphisms [PvuII (rs 2234693) and XbaI (rs 9340799)] with stroke in a South Indian population from Andhra Pradesh. The relationship between ESR1 genotypes with estradiol levels was also investigated in pre- and postmenopausal women. Methods: Four hundred patients with ischemic stroke and three hundred and eighty subjects were enrolled in this case–control study. Ischemic stroke subtypes were classified according to TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification. The ESR1 PvuII and XbaI genotypes were determined by PCR-RFLP method. Serum estradiol was measured by ELISA. Results: In case of PvuII polymorphism statistically significant difference was observed in the genotypic and allelic frequencies between patients and controls (joint analysis of men and women) (p=0.003 and 0.004 respectively). However, the XbaI genotypes and alleles did not show an association with stroke in the study population. When the analysis was carried out separately for men and women, the PvuII polymorphism did not show significant association with stroke in men; women showed a significant association. Further when women were grouped in to premenopausal and postmenopausal, the premenopausal group did not show a significant association with the polymorphism but significant association with stroke was found in postmenopausal women. A stepwise multiple logistic regression analysis confirmed these findings. Women with pp genotype had low estradiol levels in comparison with PP genotypic individuals (p<0.05). Further evaluating the association of this polymorphism with stroke subtypes, we found significant association of PvuII polymorphism with extracranial atherosclerosis, lacunar and cardioembolic stroke. Conclusion: In conclusion our results suggest the PvuII gene polymorphism is significantly associated with stroke in postmenopausal women in a South Indian population from Andhra Pradesh. The pp genotypes have average 17β estradiol levels which are significantly low in comparison with PP genotypes. Therefore postmenopausal women with a high frequency of pp genotype are more predisposed to ischemic stroke. However, this is a preliminary study and the results need to be confirmed in a larger cohort. [Copyright &y& Elsevier]

Background: Estrogen receptors (ER), progesterone receptors (PR) and the human epidermal growth factor receptor-2 (HER2) are basic breast cancer molecular markers that are also best recognized prognostic factors and predictors of type of targeted therapy to be given. The objectives are to study the correlation of expression of hormone and HER2receptors with various clinico-pathological prognostic parameters like patient's age at diagnosis, menopausal status, tumor size, histological grade and lymph node status of tumor and with each other in malignant breast lesion., Methods: For this study histopathology (HP) and immunohistochemistry (IHC) slides of excised specimens of 330 female patients with a palpable breast lump deposited to the pathology department of a hospital as a part of routine diagnostic procedure, were evaluated under the guidance of trained doctors who have minimum 5 years of experience in oncopathology. The author has no direct involvement with patients, informed consent was not necessary and data were collected after getting permission from concerned authority., Results: This study finds significant relationship between hormone receptors and all clinico-pathological prognostic parameters taken for comparison except age at diagnosis. HER2 status has significant relationship with all clinico-pathological prognostic parameters; hormone and HER2 status suggests an inverse relationship., Conclusions: Mien of hormone receptors expression in breast cancer is related with better prognostic factors such as older age, postmenopausal status, smaller tumor size, low histological grade and negative lymph node status, however the opposite is correct for HER2. Hormone receptors and HER2 have an inversely proportionate relationship with each other., (Copyright © 2020. Published by Elsevier Inc.)

Background: Targeted therapy against ER/PR/HER-2/neu for carcinoma breast is well established but there is continuing search for optimal targeted therapeutic options for triple negative breast cancer (TNBC) patients. TNBC is reported to be the most common breast cancer subtype in Indian population which is nearly twice the rate reported in Western countries. We evaluated the expression of BRCA-1 in non-familial female breast cancer patients along with down the line molecular targets (STAT 1 and 3) with the objective of identifying potential therapeutic targets in TNBC. Methods: Immunohistochemistry performed for Estrogen receptor (ER), Progesterone receptor (PR), Her-2/neu receptor (HER2), Cytokeratin (CK5/6), Ki67, BRCA1, STAT1, STAT3, pSTAT1 and pSTAT3 in 145 sporadic IDC-NOS breast cancer cases with appropriate positive and negative controls with objectives to study inter marker co-relation and their correlation with clinic-pathological variables and clinical outcomes. Results TNBC was most frequent subtype (37%) followed by equal distribution of HER2 and Luminal type B (21.7% each) and luminal A type (19.4%). BRCA nuclear loss was observed in 62.68% (89/142) and STAT1-loss in 68.6% (59/86). Cases with BRCA1 nuclear loss and STAT1-loss had larger tumor size, higher grade, axillary nodal metastasis (pN2, pN3), high Ki67 and poor clinical outcome as compared to cases with BRCA1 nuclear protein / STAT 1 expression. Expression of pSTAT1was studied in 60 cases. BRCA1 nuclear loss and STAT1 down regulation was seen in 88.3% (38/43; p=0.044). STAT 3 expression was seen in 115/137 (83.94%) cases. Association of STAT3 nuclear expression with Nottingham grade, BRCA1nuclear loss, Ki67 was found to be statistically significant. STAT 3 phosphorylation showed that STAT 3 up-regulated tumors were aggressive with larger tumor size and proliferative activity. Conclusions Therapeutic targeting of BRCA1 pathway and STAT 3 up regulation by PARP and STAT-3 inhibitors may be useful way forward in sporadic breast cancers. Total 74% (40/54) TNBC cases displayed BRCA1 nuclear loss with nine cases (9/54; 16%) harbouring STAT 3 up-regulation. Targeted agents against BRCA 1 and STAT 3 may be especially relevant for TNBC which are not only hormone treatment deprived but also have limited chemotherapy treatment options. [ABSTRACT FROM AUTHOR]

Introduction Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status are clinically used to define breast cancer subtypes and are therapeutically as well as prognostically important. The discordance of ER, PR, and HER2 between primary and the recurrent breast cancer has been recognized in studies with few reporting change in therapy as well. Despite the ongoing studies looking into the discordance rate and its implications worldwide, the data from Indian subcontinent is limited. Methods This was a prospective study carried out from September 2015 to February 2017. All recurrent (locoregional or metastatic) breast cancer patients were analyzed. Biopsy was done from the recurrent site and IHC study was performed. The discordance of ER, PR and HER2 status between primary tumor and recurrent disease were analyzed. Mc Nemar test on SPSS version 23.0 was used to see the statistical significance. Results A total of 78 patients were analyzed. Thirty five (45%) patients had only locoregional, 14 (18%) had only visceral and 29 (37%) had locoregional alongwith visceral metastasis at recurrence. The discordance rate for ER was 13.7% (n=11; p=.227). Among these, 3 (3.7%) had ER changed from positive to negative whereas 8 (10%) had change from negative to positive. The discordance rate for PR was higher with 28.7% (n=23; p=.017). Those who had receptor changed from positive to negative was 6 (7.5%) while 17 (21.2%) had change from negative to positive. The discordance of HER2 was seen in 21.2% (n=17; p=.013) with 3 (3.7%) showing change from positive to negative and 14 (17.5%) from negative to positive. Conclusion The discordance rate in our study was 13.7%, 28.7%, and 21.2% for ER, PR, and HER2 respectively. On contrary to the reported literature, a higher number of patients had receptor negative in primary to receptor positive in the recurrent specimen than converting from positive to negative. Therefore, routine biopsy and analyses for ER, PR, and HER2 status in the recurrent setting should be done in all patients, which have important implications in the management as well as prognosis. [ABSTRACT FROM AUTHOR]