Neu Expression Research Articles

Comparison of Receptor Status in Breast Carcinoma Between Premenopausal and Postmenopausal Women

Background: Breast cancer is the most prevalent cancer affecting women worldwide. The immunohistochemical status of estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2) plays a crucial role in determining breast cancer treatment options and prognosis. These receptor statuses are known to be influenced by menopausal transition. Objective: This cross-sectional comparative study aimed to assess the frequency of ER, PR, and HER2/Neu positivity or negativity and their association with menopausal status among female breast carcinoma patients. Methodology: The study was conducted over one year, from September 2021 to August 2022, at the Department of Surgery, Rajshahi Medical College, Rajshahi. A total of 50 female patients with breast carcinoma were included in the study, divided into two groups: Group A (Premenopausal women) and Group B (Postmenopausal women). Specimens were collected after modified radical mastectomy and sent to renowned laboratories for histopathological and immunohistochemical receptor assays. Data were collected through a predesigned semi-structured questionnaire and analyzed using SPSS (version 24.0). Results: The study found no significant relationship between receptor status and menopausal status or increasing age. However, a significant histopathological association was observed with receptor status, with ER and PR positivity associated with grade II tumors (p-value <0.011). The most common histopathological type was ductal cell carcinoma, and its incidence increased with parity (p-value <0.009). Conclusions: This study revealed no significant difference in hormone receptor and HER2 Neu expression between premenopausal and postmenopausal breast carcinoma patients. Further research with a larger sample size is recommended for a more comprehensive understanding of this relationship.

Expression of hormone receptors and human epidermal growth Factor2/Neu in female breast cancer patients

Overexpression of HER2/neu and estrogen receptors (ER) and/or progesterone receptors (PR) are reported to be inversely associated with breast cancer (BC). The relationship between hormone receptors and HER2/neu is attenuated by age and numerous other clinical factors. Here, we examined the link between hormone receptors and HER-2/neu in terms of an additional variable, such as the histological grades of breast tumors in women. A total of 240 breast cancer samples were obtained from the Department of Histopathology at the University of Lahore Teaching Hospital in Lahore, Punjab. Immunohistochemistry (IHC) was used to examine the expression of hormone receptors and HER-2/neu. Using the χ2 and fisher exact test, the association between hormone receptors and HER-2/neu in various age groups and histological grades was investigated. Patients that were included in this study had ages between 30 and 90 years, with a mean age of 51.89 ± 12.01 years, and were mostly having grade 1 tumors. The most prevalent type of breast cancer was invasive ductal carcinoma (95.83%). It was found that the ER, PR, and HER-2/neu were more expressive in older (above 45) and grade 1 tumors as compared to younger (≤45) and higher-grade tumor patients. HER-2 was negatively correlated with hormonal receptors in women aged >45 years old with grade-1 tumors. Hormonal receptor (ER/PR) expression is associated with HER-2/neu expression not only in older age (>45) but also in grade 1 tumors. This correlation between HER2/neu and hormone receptors that improves with age and tumor grade is useful for predicting outcomes and, likely, for guiding therapy choices.

Evaluation of the Expression EGFR, HER2/NEU and the End Effector ERK of the RAS/RAF/MAP Kinase Pathway in Prostatic Adenocarcinoma for a Possible Role as New Target Therapy.

Immunohistochemistry- using tissue microarrays- for EGFR, HER2/neu, non-phosphorylated, and phosphor-ERK, was performed on tissues from 166 patients- with primary prostatic adenocarcinoma with no prior treatment-. The results of different markers expression were correlated with the clinical and pathological parameters and were analyzed statistically. The prostatic tissue showed EGFR, HER2 neu, phosphorylated and non-phosphorylated ERK expression in 8.4%, 1.4%, 78.2%, and 83.4% respectively whether low (patchy) or high expression (diffuse). There were no significant correlations found between patient characteristics and expression of the tested markers. The negative immune reactivity for non-phosphorylated ERK and EGFR- was significantly correlated with high tumor stage (p values 0.03 and 0.01, respectively). EGFR and HER2/neu may play a limited role in prostatic adenocarcinoma as they showed positive expression in a limited number of the examined tissues specifically HER2neu. The expression of non-phosphorylated ERK (mostly weak to moderate) and phosphorylated ERK (mostly moderate to strong)- was appreciated in most cases. Thus, we suggest that anti-EGFR drugs may have a limited role in the treatment of castrate-resistant prostate cancer, but anti-MEK/ERK drugs may have more promising role as a target therapy. It is recommended to perform further molecular testing to elucidate the exact mechanism and significance of these markers.

Association of hormone receptors and human epidermal growth factor receptor-2/neu expressions with clinicopathologic factors of breast carcinoma: a cross-sectional study in a tertiary care hospital, Kabul, Afghanistan

BackgroundBreast cancer (BC) is one of the major causes of death worldwide. It is the most common cause of death before the age of 70 years. The incidence and mortality of BC are rapidly increasing, posing great challenges to the health system and economy of every nation.MethodologyA cross-sectional analytical study was conducted at the Department of Pathology and Clinical Laboratory of the French Medical Institute for Mothers and Children (FMIC) to demonstrate the association of human epidermal growth factor receptor 2 (Her2/Neu) and estrogen receptor (ER)/ progesterone receptor (PR) with clinical as well as pathological parameters among women with BC. A consecutive nonprobability sampling method was used for this study over a span of one and a half years.ResultsOne hundred twenty participants diagnosed with breast cancer were included in the study. The mean age at diagnosis was 44.58 ± 11.16 years. Out of the total patients, 68 (56.7%) were above 40 years old, 108 (90%) were married, 94 (78.3%) were multiparous, and 88 (73.3%) had a history of breastfeeding. 33.3% of cases were within the age range of menopause (40–50 years). The positive expression rates of ER, PR, and Her2/neu were found to be 48.8%, 44.6%, and 44.6%, respectively, and Her2/neu overexpression was found to be higher among ER/PR-negative cases.ConclusionIn our study, we demonstrated that among Afghan women, grade II invasive ductal carcinoma, not otherwise specified, was the most common type of BC and frequently affected women above the age of 40. We also revealed that the percentage of negative ER (50.4%), negative PR (54.4%), and concordant ER/PR-negative cases were high compared to other possibilities. Additionally, the study revealed that expression of Her2/neu was in contrast with the expression of ER and PR receptors. The findings of our study still support the importance of performing immunohistochemical stains for hormonal receptor classification in terms of better clinical outcomes and prognosis.

A study on immunohistochemical expression of HER2/Neu and p63 and its association with grade and invasiveness in case of bladder carcinoma.

Bladder cancer is a global disease, ranks as the fourth most prevalent cancer. The incidence and prevalence increase with age. Grade and aggressiveness have been found to be related with different genetic expression and mutation. To evaluate any relation of grade and invasiveness of urothelial cancer with varied expression of immune histochemical marker p63 and her2/neu. The present study was a hospital based prospective cross-sectional study. This Study was conducted from July 2021 to April 2023 in the Urology department of a tertiary care hospital. Total 90 patients undergoing trans urethral resection of bladder tumour (TURBT) were included in this study. It was found that, patients who had decreased p63 expression had high grade in tumours (93.1%) compared to patients who were expressing normal p63 (32.8%) and this was statistically significant (p < 0.0001). Tumours with decreased p63 also appeared to be more invasive, 62.1% were found to be muscle invasive. Tumours with her2 neu expression found to be more aggressive in nature, 85.7% had high grade features and 53.6% were muscle invasive. Our findings suggest that immunohistochemical expression of HER2/neu positive and decreased p63 expression were associated with high grade and invasiveness in case of bladder carcinoma.

Role of HER2/neu in Colorectal Carcinoma: A Cross-sectional Study from a Tertiary Care Centre in West Bengal, India

Introduction: In many tumours, Human Epidermal Growth Factor Receptor 2 (HER2) expression and HER2 amplification are studied as therapeutic and prognostic factors. The incidence of HER2/neu expression and its consequences in patients with colorectal carcinoma has shown conflicting evidence. Aim: To evaluate the utility of HER2/neu expression in colorectal carcinoma and to find any association between HER2/neu expression, histological grade, and stage of the tumour. Materials and Methods: This cross-sectional study was conducted on 50 cases of colorectal carcinoma. Patients undergoing surgery for colorectal tumours were selected over an 18-month period (January 2020 to June 2021) in a tertiary care hospital in Kolkata, West Bengal, India. Various clinical and demographic parameters were obtained from the patients, and the specimens were subjected to Immunohistochemical (IHC) staining for HER2/neu. The results were analysed using Statistical Package for the Social Sciences (SPSS)software version 25.0 (IBM, Armonk, New York, USA). Results: On HER2/neu IHC examination, 30 cases (60%) showed a 3+ score, 4 cases (8%) showed a 2+ score, 7 cases (14%) showed a 1+ score, and the remaining 9 cases (18%) showed a score of 0. HER2/neu expression was found in 30 cases (60%) of colorectal carcinoma. HER2/neu expression showed a significant association with the histological grade of the tumour (p-value=0.020). HER2/neu expression also showed a significant association (p-value&lt;0.001) with histological subtypes of the tumour. Conclusion: This study revealed a significant association between HER2/neu expression and histological subtypes and grade of the tumour. Moderately differentiated adenocarcinoma showed the highest expression, while mucinous adenocarcinoma and undifferentiated carcinoma showed minimal or absent HER2/ neu expression. Thus, HER2/neu can serve as a prognostic and therapeutic marker in colorectal carcinoma. In conclusion, surgery alone is not curative for patients with colorectal cancer, and additional forms of management may be required to improve patient survival. In such cases, HER2/neu expression can guide new adjuvant therapy.

Immunohistochemical markers in predicting behavior of bladder urothelial carcinoma.

Bladder cancer is the 5th most prevalent cancer among Iranian men. Finding prognostic markers to predict behavior of this cancer can help us to choose the best treatment for patients from the first place. We aimed to evaluate the correlation of immunohistochemical markers with tumor stage, grade and prognosis of disease. In this study, we reassessed the specs of proven UC among Iranian patients. Sixty specimens were collected, contained of 30 low grade and 30 high grade urothelial carcinomas. All slides were assessed by immunohistochemistry study for p21, p27, Her-2/neu, E-cadherin, and CD10. Data were analyzed by SPSS 18.0 and a p-value < 0.05 was considered significant. We evaluated 60 patients in this study with mean age of 66±11 years and majority of them are men. High expression of p27 showed significant correlation with LGUC (P=0.030). HGUC related with high expression of Her-2/neu, CD10 and aberrant expression of E-Cadherin (P<0.0001). Aberrant E-Cadherin and high expression of CD10 are associated with higher tumor stage (P=0.000). CD10 intensity was the only immunohistochemical markers to predict prognosis (P=0.010). In the present study, CD10 intensity is the only marker that directly predicts the prognosis. The higher intensity leads to poor prognosis (recurrence or metastasis). More studies must be done in this aspect to resolve the controversies and clarify the role of immunohistochemical markers in predicting BC behaviors.

Preclinical and Clinical Observations Implying Combination Therapy to Enhance the Efficacy of the Her-2/neu B-Cell Peptide-Based Vaccine HER-Vaxx and to Prevent Immune Evasion.

Her-2/neu-targeting therapy by passive application with trastuzumab is associated with acquired resistance and subsequent metastasis development, which is attributed to the upregulation of tumoral PD-L1 expression and the downregulation of Her-2/neu. We aimed to investigate this association, following active immunization with our recently constructed B-cell peptide-based Her-2/neu vaccines in both preclinical and clinical settings. Immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and combined positive score (CPS) were applied to evaluate Her-2/neu and PD-L1 expression using a murine syngeneic tumor model for Her-2/neu lung metastases and tumor biopsies from a gastric cancer patient with disease progression. A significant and concomitant reduction in Her-2/neu and the upregulation of PD-L1 expression was observed in vaccinated mice after 45 days, but not after 30 days, of metastases development. A significant increase in tumor-infiltrating B lymphocytes was observed at both time points. The downregulation of Her-2/neu and the upregulation of PD-L1 were observed in a patient's primary tumor at the disease progression time point but not prior to vaccination (Her-2/neu IHC: 3 to 0, FISH: 4.98 to 1.63; PD-L1 CPS: 0% to 5%). Our results further underline the need for combination therapy by targeting PD-L1 to prevent metastasis formation and immune evasion of Her-2/neu-positive and PD-L1-negative tumor cells.

Active Gαi/o Mutants Accelerate Breast Tumor Metastasis via the c-Src Pathway.

Constitutively active mutations in the Gαi2 and GαoA subunits of heterotrimeric G proteins have been found in various human cancers, including breast cancer, but their precise roles in tumor formation, progression, and metastasis remain poorly understood. This study focused on GαoAR243H and Gαi2R179C mutants in breast cancer. These mutants alone were insufficient to initiate mammary tumor formation in mice. However, when introduced into transgenic mouse models of breast cancer induced by Neu expression or PTEN loss, the Gαi2R179C mutant notably enhanced spontaneous lung metastasis, without affecting primary tumor initiation and growth. Ectopic expression of the GαoAR243H and Gαi2R179C mutants in tumor cells promoted cell migration invitro and dissemination into multiple organs invivo by activating the c-Src signaling pathway. These mutants activate c-Src through direct interaction, involving specific residues in the switch domains II of Gαi subunits, which only partially overlap with those involved in inhibiting adenylyl cyclases. This study uncovers a critical role of Gαi/o signaling in accelerating breast cancer metastasis through the c-Src pathway. These findings hold clinical significance as they may pave the way for personalized therapies targeting c-Src to inhibit breast cancer metastasis in patients with active Gαi/o mutations or elevated Gαi/o signaling.

The utility of a deep learning-based approach in Her-2/neu assessment in breast cancer

IntroductionHER-2/neu is a protein present on the surface of specific cancer cells and has been linked to the development and progression of certain cancer types. It is present in 15 to 20% of breast cancers and is clinically significant due to the availability of multiple anti-Her2 treatment options. Immunohistochemistry (IHC) is the most commonly used method to evaluate and quantify the expression of Her-2/neu. Although IHC is well-standardized in clinical practice, it is still subjected to inter-observer variability. Automating Her-2/neu scoring can improve accuracy, efficiency, consistency, and cost-effectiveness while reducing pathologists' workload. Materials and MethodsA deep learning-based automatic framework was utilized for the automatic detection of Her-2/neu score from whole slide images (WSI). The framework consists of three phases: identification of tumor patches, scoring of tumor patches, and Her-2/neu score prediction for whole slide images (WSI) based on the distribution of each score. This work used the dataset from the University of Warwick HER2 challenge contest. Two expert pathologists evaluated all 86 WSIs and assigned Her-2/neu scores to them. In addition, patches were generated from 50 WSIs and annotated individually by the pathologists. A total of 6641 extracted patches were generated out of which, 947 were labeled as 0, 327 as 1+, 1401 as 2+, 2950 as 3+, and 1016 were marked for discarding. Four pre-trained image classification models, namely DenseNet201, GoogleNet, MobileNet_v2, and a Vision Transformer based model, were fine-tuned, and tested on the generated patches. In order to predict the Her-2/neu score of the entire WSI, a random forest classifier was trained to predict the Her-2/neu score from the percentages of patches of each score present in the whole slide image. ResultsIn patch classification performances, the vision transformer-based model outperformed the other models by achieving an accuracy of 92.6% on tumor patch classification and 91.15% on patch score classification. The random forest classifier achieved an accuracy of 88% on four score classification (0, 1+, 2 + and 3 + ) and 96% on three score classification (0/1+, 2 + and 3 + ). ConclusionThe proposed deep learning-based framework for the automatic detection and evaluation of Her-2/neu expression in breast cancer obtained encouraging results. This framework has the potential to be used as a prognostic tool, providing a cost-effective and time-efficient alternative for generating clinically relevant results. However, additional research is required to assess the applicability of this pipeline in different contexts.

A phase 2 multicenter study of docetaxel-PM and trastuzumab-pkrb combination therapy in recurrent or metastatic salivary gland carcinomas.

Salivary duct carcinoma (SDC) is uncommon but is the most aggressive subtype of salivary gland carcinomas. The high positivity rate for human epidermal growth factor receptor 2 (HER2) led to an investigation of the efficacy of HER2-targeted agents. Docetaxel-PM (polymeric micelle) is a low-molecular-weight, nontoxic, biodegradable, and docetaxel-loaded micellar formulation. Trastuzumab-pkrb is a biosimilar to trastuzumab. This was a multicenter, single-arm, open-label phase 2 study. Patients with HER2-positive (immunohistochemistry [IHC] score of ≥2+ and/or HER2/chromosome enumeration probe 17 [CEP17] ratio of ≥2.0) advanced SDCs were enrolled. Patients received docetaxel-PM (75mg/m2 ) and trastuzumab-pkrb (8mg/kg in the first cycle and 6mg/kg in subsequent cycles) every 3weeks. Primary end point was objective response rate (ORR). A total of 43 patients were enrolled. The best objective responses were partial response in 30 (69.8%) patients and stable disease in 10 (23.3%) patients, leading to an ORR of 69.8% (95% confidence interval [CI], 53.9-82.8) and a disease control rate of 93.0% (80.9-98.5). Median progression-free survival, duration of response, and overall survival were 7.9 (6.3-9.5), 6.7 (5.1-8.4), and 23.3 (19.9-26.7) months, respectively. Patients with HER2 IHC score of 3+ or HER2/CEP17 ratio ≥2.0 demonstrated better efficacies compared to those with HER2 IHC score of 2+. Thirty-eight (88.4%) patients experienced treatment-related adverse events (TRAE). Because of TRAE, nine (20.9%), 14 (32.6%), and 19 (44.2%) patients required temporary discontinuation, permanent discontinuation, or dose reduction, respectively. The combination of docetaxel-PM and trastuzumab-pkrb demonstrated promising antitumor activity with a manageable toxicity profile in HER2-positive advanced SDC. Salivary duct carcinoma (SDC) is uncommon but is the most aggressive subtype of salivary gland carcinomas. SDC shares morphological and histological similarities with invasive ductal carcinoma of breast, which led to an investigation of hormonal receptor and human epidermal growth factor receptor 2 (HER2)/neu expression status in SDC. In this study, patients with HER2-positive SDC were enrolled and treated with combination of docetaxel-polymeric micelle and trastuzumab-pkrb. Promising antitumor activities were shown with objective response rate of 69.8%, disease control rate of 93.0%, median progression-free survival of 7.9months, median duration of response of 6.7months, and median overall survival of 23.3months.

Spatial distribution of Her-2/neu and PD-L1 expression in lung metastases after active immunization with a Her-2/neu-targeting mimotope-based multipeptide B-cell vaccine in a mouse model

Spatial distribution of Her-2/neu and PD-L1 expression in lung metastases after active immunization with a Her-2/neu-targeting mimotope-based multipeptide B-cell vaccine in a mouse model

Evaluation of Cyclin D1 and Human Epidermal Growth Factor Receptor 2 Neu Protein Expression in Head and Neck Squamous Cell Carcinoma.

Background Head and neck cancers are highly aggressive, frequently occurring cancers that are prevalent worldwide. The mainstay of their treatment is surgery, followed by adjuvant therapy. Various studies have documented the usefulness of molecular markers in carcinogenesis and have proven helpful in the diagnosis and treatment of head and neck cancers. Cyclin D1 is a proto‑oncogene, overexpression of which leads to the accelerated entry of cells in the S phase of the cell cycle, causing uncontrolled proliferation of the cells. The dysregulation of human epidermal growth factor receptor 2 (HER2) neu is also related to multiple features of malignancy, including loss of cell cycle control, induction of angiogenesis, and resistance to apoptotic stimuli. This study seeks to identify a subset of patients with a bad prognosis who may require aggressive treatment strategies. Aim This study aims to determine the proportion of the expression of cyclin D1 and HER2 neu in head and neck squamous cell carcinoma (HNSCC) and analyze the association between the expression of cyclin D1 and HER2 neu using histological grading, tumor, node, and metastasis (TNM) staging, and nodal status of the tumor. Furthermore, this study also aims to document clinical outcomes, such as locoregional control, depth of invasion (DOI), and regional metastasis regarding the expression of cyclin D1 and HER2 neu in HNSCC. Setting and design This study is a laboratory-based observational study. Materials and methods Seventy histologically proven cases of HNSCC were studied for various histopathological parameters, and further immunohistochemistry (IHC) was performed for cyclin D1 and HER2 neu. The expression and intensity of cyclin D1 were multiplied, and the total score was derived. The College of American Pathologists/American Society of Clinical Oncology (CAP/ASCO) guidelines for HER2 neu testing in breast cancer were used for scoring. Result Out of 70 cases, 52 (75%) demonstrated strong and moderate positivity for cyclin D1, and the p-values were 0.017, 0.001, and 0.032 for depth of invasion, TNM stage, and lymph node metastases, respectively,for cyclin D1, which was considered statistically significant. For HER2 neu, five out of 70 cases were positive, and the p-value was significant for depth of invasion (0.008). Conclusion The expression of the above marker cyclin D1 increases with stage, DOI, and positive lymph node status. Hence, cyclin D1 immunoexpression can be helpful in the early assessment of HNSCC behavior and can serve as an independent prognostic marker. Furthermore, it was observed that HER2 neu was significant with an increase in depth of invasion of tumor, which, in the American Joint Committee on Cancer (AJCC) eighth edition, is considered an important factor for determining the stage of the tumor. Further research is needed to examine whether HER2 neu can act as a prognostic factor for HNSCC and if it can be targeted for treatment options.

Immunohistochemical Study of HER-2/NEU Expression in Urothelial Bladder Carcinoma and its Correlation with Histopathological Grade

Background: Human epidermal growth factor receptor 2 (HER2) overexpression and amplification have been considered as a therapeutic and prognostic target in a quantity of tumors although conflicting data exist about the incidence and clinical consequence of HER2/neu status in the patients. The growth risk of bladder cancer is age dependent. In general, adolescent and young adults tend to develop well differentiated non-invasive, rather than invasive bladder cancer. Objectives: The aim of this study is to assess the Immunohistochemical study of HER-2/NEU Expression in urothelial bladder carcinoma and its correction with histopathological Grade. Methods: This was a cross sectional study. Patients with paraffin blocks of urinary bladder tissue which were histologically diagnosed as urothelial carcinoma at the Department of Pathology, BIRDEM and other private laboratories were included in our study during the period of January 2016 to December 2018. Results: This study shows that, a total of 56 histologically diagnosed cases of urothelial carcinoma were included. There were 34 cases (60.7%) of high grade and 22 cases (39.3%) of low-grade urothelial carcinomas. The age of the patient ranged from 23 years to 98 years (mean 66.34±15.3 years). Majority of patients (50.98 %) belonged to 61 to 80 years age group. High grade tumors were predominantly seen at an older age. There were 42 males (75.0%) and 14 females (25.0 %) with a male to female ratio of 3:1. Conclusions: Significant correlation in expression of HER-2/Neu was found with grading of urothelial carcinoma. A positive HER-2 status is associated with aggressive urothelial carcinoma and provides independent prognostic information for urothelial carcinoma recurrence and mortality.

Molecular and Immunohistochemical Alterations in Breast Cancer Patients in Upper Egypt.

Breast cancer (BC) plays a major public health in Egyptian woman. In Upper Egypt, there is an increase in incidence of BC compared to other Egyptian areas. Triple-negative BC, estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-neu-negative, is a high-risk BC that lacks the benefit of specific therapy that targets these proteins. Accurate determination of Caveolin-1(Cav-1), Caveolin-2 (Cav-2) and HER-2/neu status have become of major clinical significance in BC by focusing about its role as a tumor marker for response to different therapies. The present study was performed on 73 female BC patients in the South Egypt Cancer Institute. Blood samples were used for Cav-1, Cav-2, and HER-2/neu genes amplification and expression. In addition, immunohistological analysis of mammaglobin, GATA3, ER, PR, and HER-2/neu was done. There was a statistically significant association between Cav-1, 2 and HER-2/neu genes expression and the age of patients (P< 0.001). There are increase in the level of Cav-1, 2 and increase in HER-2/neu mRNA expression in groups treated with chemotherapy and group treated with both chemotherapy and radiotherapy compared to each group baseline level of genes mRNA expression before treatment. On the contrary, the group treated with chemotherapy, radiotherapy and hormonal therapy revealed increase on the level of Cav-1, 2 and HER-2/neu mRNA expression when compared with their baseline for the same patients before treatment. Noninvasive molecular biomarkers such as Cav-1 and Cav-2 have been proposed for use in the diagnosis and prognosis for women with BC.

Analysis of Breast Cancer Receptors Status and Molecular Subtypes Among Female Population

One of the leading cause of deaths in women is breast cancer. The incidence and prevalence of cancer is increasing day by day. The aim of this research was to analyse the relationship between HRS (hormonal receptor status) and age in females suffering from breast cancer. It was a cross-sectional study conducted at surgical department, LUMHS, Jamshoro, Sindh, Pakistan. The 200 females diagnosed with breast cancer were included in research. The mean age of the study sample was observed to be 48.68 ± 9.54 years. Out of 200 females, 79 (39.5%) females had positive expression of “ER (estrogen receptor)” while 80, (40%) had positive “PR (progesterone receptor)” expression and 41(20.5%) females were associated with “positive expression of HER2/neu (human epidermal growth factor receptor 2)”. The age group of 41-50 years showed (30.4%) highest ratio of positive ER followed by (24%) PR and (17.5%) “HER/2 neu expression” respectively. A statistically significant correlation was found between ER expression and age and (p=0.013), PR expression and age and (p=0.002) while HER/2 neu expression showed insignificant correlation (p=0.231). The research also found that most of the females in their 40s were suffering from breast cancer also the older women had positive were “estrogen receptor (ER), progesterone receptor (PR), and HER2/neu expression” as compared to younger females but there are high chances of survival if breast cancer is diagnosed and managed timely. To do so awareness regarding self-care and self-analysis for women is important to prevent the prognosis of breast cancer. Keywords: Breast Cancer, hormonal receptor status, estrogen, progesterone

Expression of Her-2/NEU in Patients With Primary Non-small Cell Lung Cancer (Nsclc)

Introduction: Now a days immunohistochemistry and genomic testing for patient with Non- Small Cell Lung Cancer (NSCLC) is becoming new standard of care in clinical decision making. A renewed interest has been emerging on the human epidermal growth factor-2 (HER2) pathway. Aim of this present study was clinicopathological correlation of HER-2/neu expression by IHC in NSCLC. Method: This was a Cross sectional and observational study done at Sir Salimullah Medical College and National Institute of Disease of the Chest and Hospital (NIDCH) and other private hospitals in Dhaka city during July / 2014 to June / 2016. Adult of both gender with histologically diagnosed as a case of NSCLC was include in the study. Immunohistochemistry was done to see the positivity for HER/neu and clinical characteristics were observed. Result: A total 45 patients with NSCLC were enrolled in the study. Male was 77.8% (n=35) and female was 22.2% (n=10). The mean age was 55.67 (SD± 12) years and mean age of male was higher compared to female (57.54±11.64 years verses 49.1±11.38 years). Most of the male were smokers (71.1%) and female were nonsmokers (90%). 57.78% (n=26) of patients and 42.22% (n=19) of patients had adenocarcinoma and squamous cell carcinoma respectively. Most squamous cell carcinoma patients were elderly, had wasting and having higher TNM staging. Serum LDH level was higher with advance staging and grading. Only 8.89% (n=4) had HER-2/neu positive expression affected by male. Patients with HER 2/neu positive expression were relatively older (mean age 62.5±17.08). However, there were equal in histopathological categorization (50% SCC and 50% Adenocarcinoma). Mean LDH was slightly higher in HER-2 positive patients was compared to HER-2 negative patients (569.5±232.6 versus 469.7±181.8). Conclusion: About nine percent of patients having HER-2/neu positive was relatively older and had more high level of LDH. A large-scale study should be conducted in Bangladeshi population to characterize epidemiological, clinicopathological feature in patients with NSCLC with HER-2 expression. J Dhaka Med Coll. 2021; 29(1): 99-110

Expression of BRCA1 by immunohistochemistry and its association with ER, PR, Her2neu status in infiltrative ductal carcinoma of breast.

Breast cancer is a heterogeneous disease, which differs in its clinical behaviors and responses to treatment and outcome. The prognosis of breast cancer depends on histopathological parameters and molecular subtypes. Among more than 300 genes, which are involved in the pathogenesis of breast cancer tumor suppressor gene such as BRCA1 is known to play a significant role in hereditary cancers. However, its role in sporadic cases of infiltrating ductal carcinoma is yet to be established. To evaluate the expression of BRCA1 in infiltrative ductal carcinoma and to analyze the association of BRCA1 with histopathological parameters and estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor2 (Her2) neu expression. This was a laboratory-based exploratory study in which 56 patients with infiltrative ductal carcinoma who underwent radical mastectomy from October 2019 to July 2021 were included. Patients with chemotherapy and radiotherapy, trucut biopsies, and incomplete patient details were excluded. Immunostaining for BRCA1 was performed. Individual clinicopathological parameters were compared with the BRCA1 mutation. Statistical analysis was done using SPSS 22. A P value of < 0.05 was considered statistically significant. Among 56 cases of IDC, 18 cases (32.1%) showed BRCA1 mutation. BRCA1 mutation was associated with postmenopausal age, larger tumor size, lower tumor grade, and higher tumor staging. When we analyzed the biomarkers with BRCA1 mutation, it showed a negative association with ER, PR, and Her2 neu and a high Ki67 proliferation index. No family history of breast carcinoma was seen in 34/56 patients where history was available. Our study showed BRCA1 mutation in 32.1% and associated with postmenopausal age group, larger tumor size, and higher staging and negative hormonal status of breast carcinoma.

Expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2/neu in gallbladder carcinoma in North Indian population

Background: Gallbladder carcinoma (GBC) although rare is most frequent malignant neoplasm of biliary tract system and sixth most common malignancy of digestive tract. GBC is more common in females and there are studies which show expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 neu (HER2/neu) in GBC suggesting possible molecules for targeted therapy, but results are inconsistent. Aims and Objectives: The aim of this study was to find out expression of ER, PR, and HER2/neu in GBC in North Indian population and their possible association with clinicopathological features. Materials and Methods: A total 59 resected cases of GBC diagnosed by histopathological examination were included in the study. Expression of ER, PR, and HER2/neu was accessed by immunohistochemistry method and correlated with various clinicopathological features. Results: ER expression was absent in all GBC cases. PR expression was present in only one case. Positive expression of HER2/neu was present in 13 (22%) cases, in which 12 cases were of conventional adenocarcinoma and one case was of papillary adenocarcinoma. Well and moderately differentiated tumor had significantly higher HER2/neu expression as compared to poorly differentiated tumors (P = 0.001). Pre-obese patients had significantly higher HER2/neu expression as compared to non-obese patients (P = 0.008). Conclusion: In our study, there was no expression of estrogen and PR in GBC in North Indian population. Although small in number, there is a subset of patients who overexpress HER2/neu receptor that may benefit from targeted therapy.

PIK3CA mutations in breast cancer with low HER2 / neu expression

Introduction. Disturbances in the PI3K-dependent (PI3K – phosphoinositide 3‑kinase) cascade are characteristic of all types of breast cancer. In particular, 30–40 % of patients with advanced / metastatic hormone-positive HER2‑negative (HER2 – human epidermal growth factor receptor 2) breast cancer carry PIK3CA mutations in tumor cells. The detection of these mutations in patients with hormone-positive HER2‑negative breast cancer is of great clinical importance, since they are a predictor of tumor sensitivity to the PI3K inhibitor alpelisib. According to the HER2 / neu protein expression status, all patients with hormone-positive HER2‑negative breast cancer can be divided into two groups – with low expression of HER2 / neu (scores 0, 1+ or 2+ per immunohistochemical analysis and negative result of in situ hybridization) and with a complete lack of expression of this protein.Aim. To establish whether there are differences in the nature and prevalence of PIK3CA mutations in patients in these two groups.Materials and methods. The study was carried out on 32 breast cancer samples with a luminal HER2‑negative immunophenotype, which were divided into two groups – with low HER2 / neu expression (n = 15) and with a complete absence of HER2 / neu expression (n = 17). PIK3CA mutations were determined using the commercially available cobas PIK3CA MutationTest kit (Roche, Switzerland) by real-time polymerase chain reaction on paraffin block material (tissue biopsy).Results. Mutations of the PIK3CA gene were detected in 37.5 % of cases, of which p.E542K mutation was detected in 2 cases; p.E545X – in 3, p.H1047X – in 6 and p.N345K – in 1. Analysis of the mutational status of both groups revealed statistically significant differences in the quantitative distribution of PIK3CA mutations. The frequency of PIK3CA mutations was significantly higher in tumors with low expression of HER2 / neu (p = 0.0268). Thus, characteristic genetic changes have been identified for a group of patients with HER2‑low breast cancer. These changes are potential targets for therapy, which is important for clinical practice, as it opens up new therapeutic possibilities for breast cancer patients with low HER2 / neu expression.