HER2-neu Expression Research Articles

Immunohistochemical Expression of ROS1 in invasive ductal carcinoma of breast in association with hormonal receptor status and Her2Neu expression

Objective: To determine the frequency of immunohistochemical expression of ROS1 in invasive ductal carcinoma of the breast in relation to hormonal receptor status and HER2 expression. Study Design and Setting: Descriptive cross-sectional study. Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi from May 2022 to Dec 2022. Methodology: This study was conducted on a sample size comprising 137 patients diagnosed with invasive breast carcinoma (ductal carcinoma) on histopathological biopsy specimen. Immunohistochemistry was performed using ROS1, estrogen receptor, progesterone receptor and HER2 antibodies on patients’ tissue samples. Results were interpreted by two independent histopathologists. Finally data was analyzed using SPSS version 25. Results: The mean age of sample population was 50.85 ± 12.17 years. 131 patients were women and 6 were men. ROS1 was positive in 54 cases. ROS1 shows weak staining in 41 cases and moderate to strong staining in 13 cases. ER and PR showed no significant statistical correlation with ROS1 expression. HER2 was positive in 37 cases, equivocal in 11 cases and negative in 89 cases. A significant statistical correlation was seen between ROS1 and HER2 as 23 of HER2 positive cases showed ROS1 expression (p=<0.001). Conclusion: Significant number of ROS1 expressing cases in invasive breast carcinoma can be more revealing in the understanding of pathogenesis of breast carcinoma. In addition, it can also lead to use of certain recent tyrosine kinase inhibitors for treatment of this most common carcinoma in females.

Association of hTERT expression, Her2Neu, estrogen receptors, progesterone receptors, with telomere length before and at the end of treatment in breast cancer patients.

Breast cancer shows significant clinical, morphologic, and molecular variation. Telomeres are nucleoprotein complexes composed of hexanucleotide repeat DNA sequence, TTAGGG, and numerous telomere-associated proteins. The maintenance of telomere length is carried out by a ribonucleoprotein called telomerase, which consists of two main components: a catalytic subunit called hTERT (human telomerase reverse transcriptase) and an RNA template called hTR (human telomerase RNA). The importance of evaluating hTERT expression lies in its potential therapeutic application, being an attractive target due to its almost non-existent expression in normal somatic cells. It is also expected that the anti-neoplastic effect would appear earlier in neoplastic cells with shorter telomeres. Additionally, a significant relationship has been observed between Her2-Neu overexpression and Her2-Neu positivity, which could suggest new combined therapies.The aim of this study was to detect the expression of hTERT, estrogen receptor (ER), progesterone receptor (PR), and HER2-Neu in neoplastic breast tissue embedded in paraffin before treatment and to investigate the relationship between them and with baseline and post-treatment telomere length, as well as with various clinicopathological parameters. A cross-sectional-correlational, 21 women diagnosed with breast cancer at the Oncology Service of the High Specialty Medical Unit No. 1 of Bajio of the Mexican Institute of Social Security. The study complies with the Helsinki Declaration and was approved by the Institutional Ethical Committee of the Mexican Institute of Social Security (R-2019-1001-127). A peripheral blood sample was obtained before oncological treatment and at the end of oncological treatment for the measurement of telomere length by extracting DNA from leukocytes, was performed by the quantitative polymerase chain reaction (PCR) method described by Cawthon. Tumor samples were collected from each patient at the oncology department for immunohistochemical determination of biomarker expression (ER, PR, Her2/neu) and hTERT. Of the 21 cases included in the study, the median age was 57.57 years. Eighteen cases were classified as invasive ductal carcinoma NOS (85.71%), 10 were histologic grade 2 (47.61%), 16 cases were hormone receptor positive (76.19%), 7 were Her2Neu positive (33.33%), and only 2 cases were triple negative (9.52%). Positive hTERT expression was detected in 11 cases (52.38%) and was negative in the remaining cases. A significant association was identified between hTERT-positive cases and Her2-Neu positive cases (p = 0.04). Baseline and post-treatment telomere lengths showed a significant difference using the non-parametric Wilcoxon t-test (p = 0.002). In hTERT-positive cases, there was significant telomere shortening at the end of oncological treatment (6.14 ± 1.54 vs. 4.75 ± 1.96 Kb, p = 0.007). Positive hTERT immunostaining cases were associated with poor prognostic factors, such as Her2-Neu overexpression and post-treatment telomere shortening. In the future, hTERT immunostaining could be used to select patients for therapies with antagonistic effects on hTERT, as well as in the selection of more appropriate chemotherapy regimens for patients who express it.

Immunohistochemical expression of CD44 in invasive breast carcinoma

Background: In India, breast cancer forms the most common malignancy, accounting for 28.2% of all female cancers. Breast cancer consists of phenotypically diverse group of diseases. Due to different relapse abilities, doubling times, and different infiltrative capacities, it is important to identify potential biomarkers that could be used to screen high-risk patient and predict breast cancer prognosis in conjunction with classical pathological parameters. Aims and Objectives: The present study was conducted to evaluate immunohistochemical expression of CD44 in breast carcinoma and to correlate CD44 expression with other clinicopathological parameters and molecular classification of carcinoma breast. Materials and Methods: The present study was a prospective descriptive study conducted on 100 cases of carcinoma breast diagnosed on modified radical mastectomy specimens that were submitted to the Department of Pathology, Pt. B. D. Sharma, PGIMS, Rohtak, Haryana, over the period of 2 years. Results: Out of 100, 64 cases (64%) were CD44 positive. Out of these 64 cases, 9 (9%) cases were 1+, 34 (34%) cases were 2+, and 21 (21%) cases showed 3+ positive expression of CD44 in tumor cells. Loss of CD44 expression was seen in 36 (36%) cases. A statistically significant association of CD44 was seen with multifocality of the tumor, negative estrogen receptor/progesterone receptor (ER/PR) expression, and molecular subtypes. No statistically significant association of CD44 was seen with age, side of tumor, lymph node metastasis, lymphovascular invasion, ductal carcinoma in situ and Ki67, and HER2neu expression. Conclusion: A high CD44 expression in breast carcinoma correlates with aggressive tumor characteristics such as multifocality, negative ER/PR expression, and belonging to the basal subtype which is associated with poor prognosis. Conversely, low CD44 expression is linked to Luminal A and Luminal B subtypes which have good prognosis. These indicate the role of CD44 as a prognostic biomarker in the carcinoma breast.

CURRENT DRUG THERAPY OPTIONS FOR DISSEMINATED HER2-POSITIVE BREAST CANCER AT THE KAZAKH SCIENTIFIC RESEARCH INSTITUTE OF ONCOLOGY AND RADIOLOGY: A CLINICAL CASE

Relevance: Distant outcomes of treatment for Her2neu-positive metastatic breast cancer are improving due to access to innovative drug therapies. The study aimed to demonstrate the initial experience of treating a patient with progressive disseminated hormone receptor-positive breast cancer expressing HER2 (3+) and nearly exhausted options for anti-tumor drug therapy using trastuzumab deruxtecan. Methods: The paper describes a clinical case of a female patient born in 1977 who was diagnosed with Stage IV breast cancer (T1N1M1), invasive ductal carcinoma, and treated at the Kazakh Institute of Oncology and Radiology (Almaty, Kazakhstan). Immunohistochemical luminal subtype “B” with Her2neu (3+) expression. Metastatic involvement of skeletal bones with pain syndrome, lungs, liver, axillary, parasternal, and para-mediastinal lymph nodes. Since June 2023, monoclonal antibody conjugate trastuzumab deruxtecan therapy was initiated. The efficacy of fifth-line therapy was assessed using RECIST 1.1 before and during treatment. According to RECIST 1.1., target lesions included a conglomerate of hyperplastic axillary lymph nodes on the right, measuring 1.6 cm, parasternal lymph node 1.6 cm, a lesion in the parenchyma of the lower lobe of the left lung 1.3 cm, lesions (n=2) in the parenchyma of segment 2 of the left liver lobe 1.8 cm and 3.6 cm. Non-target lesion: hyperplastic para-mediastinal lymph nodes SLD 9.9 cm. Results: Pain syndrome was completely relieved after treatment. According to RECIST 1.1. in April 2024, after 11 courses of therapy, target lesions showed size reduction: conglomerate of hyperplastic axillary lymph nodes on the right decreased to 1.0 cm, lesion in the parenchyma of the lower lobe of the left lung increased to 2.7 cm, parasternal lymph node was not visualized, lesions (n=2) in the parenchyma of segment 2 of the left liver lobe measured 1.6 cm and 2.7 cm. Non-target lesion: hyperplastic para-mediastinal lymph nodes were not visualized. Conclusion: According to the clinical study data (DESTINY-Breast02), applying antibody-drug conjugate (ADC) demonstrates better objective response and progression-free survival time in patients previously treated with trastuzumab and taxanes.

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.

HER2-neu Expression and Survival in Colorectal Cancer in the South of Egypt; Immunohistochemistry and Genetic Study.

Colorectal cancer (CRC) is a major public health problem and one of leading cancer related death all over the world. One of the prognostic parameters that play a role in different types of cancer is HER2. However, the role of HER2 in CRC and its relation with clinicopathological features and survival is conflicting. We hypothesize that HER2 has different patterns of expression in CRC which may affect the prognosis of patients. We studied sixty specimens of colorectal carcinoma for HER2 immunohistochemistry and gene amplification and correlate it with clinicopathological features and patients` survival. Our data showed that negative HER2 expression was statistically associated with female gender (P = 0.010) and low & intermediate tumor budding (P = 0.030). There was a statistically significant relation between HER2 IHC and HER2 FISH amplification (P=0.000). Although neither HER2 immunoexpression and FISH amplification showed significant relation with overall survival nor disease free survival, HER2 amplified CRCs tended to have a worse survival compared with negative CRCs (40 months versus 50 months). The presence of male gender, lymphovascular invasion, nodal metastasis and distant metastasis (P = 0.013, 0.006, 0.006 and 0.000 respectively) were significantly statistically associated with poor overall survival. The presence of tumor grade III and high tumor budding (P = 0.035 and 0.007 respectively) were significantly statistically associated with shorter disease free survival. Our results showed that HER2 IHC 3+ staining is highly predictive of HER2 gene amplification in colorectal carcinomas. There is a tendency towards poorer prognosis in amplified HER2 CRC cases.

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.

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.

Expression of GATA3, p63, E-cadherin and Her2Neu Immunohistochemical Stains in Urothelial Carcinoma and their Relationship with Histological Grading and Prognosis- A Cross-sectional Study

Introduction: Urinary bladder cancer is the 10th most common cancer worldwide. Cystoscopy and biopsy/Transurethral Resection of Bladder Tumour (TURBT) are the best techniques for diagnosing and staging urinary bladder cancers. Urothelial Carcinomas (UC), particularly in transurethral resection biopsies, can pose diagnostic difficulties due to limited material. Immunohistochemistry (IHC) plays a valuable role in these settings, and many immunostains are being utilised for diagnostic evaluation. However, the relationship of these immunomarkers with histological grade and their prognostic utility has not been adequately explored. Aim: To analyse expression of Her2Neu, E-cadherin, p63, and GATA3 in UC and its relation with histological grading and prognosis. Materials and Methods: This was an observational crosssectional study conducted in the Pathology Department of IPGMER and SSKM Hospital, Kolkata, West Bengal, India over two years (November 2020-October 2022). Samples of 100 bladder carcinoma patients with predominant TURBT specimens were included in the study. The histopathological reports and tumour grading were done according to the World Health Organisation (WHO) classification of urinary bladder tumours. The Formalin Fixed Paraffin-embedded (FFPE) sections of the tumour blocks were subjected to IHC staining, and the results were interpreted accordingly. Statistical analysis was performed with the help of the Statistical Package for Social Sciences (SPSS), IBM (version 25.0). Unpaired t-test and Z-test (Standard Normal Deviate) were used to test the significant difference between two proportions. Results: The mean age of the study population was 59.69±14.53 years, and there was a male preponderance (male: female=3.54:1). Histopathological examination revealed 55% to be of low-grade morphology. Overall, 53% of cases were in T1 stage, and the rest were in T2 stage. On IHC analysis, E-cadherin showed a statistically significant decrease in intensity with increasing grade (p-value &lt;0.001) and T stage of UC (p-value &lt;0.001), but there was no statistically significant relationship between Her2Neu expression and tumour grade/ stage (p-value 0.5764 and 0.5663, respectively). A statistically significant relationship was observed between GATA3 and p63 scores with the grade and T stage of the tumour, i.e., GATA3 positivity increased with increasing grade and T stage of the tumour (p-value &lt;0.001 in both), and there was a loss of p63 with advancing grade and stage of the tumour (p-value &lt;0.001 in both). Conclusion: GATA3, p63, and E-cadherin can be used as prognostic markers in UCs. No significant relationship was found between Her2Neu expression and tumour grade in UC.

Potential Role of AKR1B1 Gene Methylation in Diagnosis of Patients With Breast Cancer.

In addition to the great challenge of early diagnosis and prognosis in breast cancer (BC), the role of gene promoters in BC remains largely unexplored. This study aimed to evaluate aldo-keto reductase family 1 member B1 (AKR1B1) methylation as noninvasive biomarker for early BC diagnosis. A total of 200 (120 with BC, 40 with benign breast diseases, 40 healthy) Egyptian women were enrolled. AKR1B1 methylation level was determined using EpiTect Methyl II QPCR assay quantitative polymerase chain reaction. Findings revealed that hypermethylation AKR1B1 was reported to be associated (P < .0001) with BC cases (93.2 [75.4-98.6]) compared with benign (23.9 [22.6-48.3]) or healthy (15.5 [10.6-16]) controls. It had a great diagnostic power (area under the curve [AUC] = 0.909) that was superior to cancer antigen (CA) 15-3 (AUC = 0.681) and carcinoembryonic antigen (CEA) (AUC = 0.539). Interestingly, AKR1B1 hypermethylation was reported to be significant in identifying BC early stages (AUC = 0.899) and grades (AUC = 0.903). Independent to hormonal status and HER2neu expression, AKR1B1 hypermethylation was related to some tumor severity features, including advanced stages, high histological grades, and lymph node invasion. Also, AKR1B1 high degrees of methylation were significantly correlated with the increase in CEA (r = .195; P = .027), CA-15.3 (r = .351; P = .0001) and tumor stages (r = .274; P = .014), grades (r = .253; P = .024), and lymph node invasion (r = .275; P = .014). This study revealed that aberrant AKR1B1 methylation could facilitate early BC detection from benign br0east disorders. Hypermethylated AKR1B1 was related to BC aggressiveness suggesting its potential role as diagnostic and prognostic BC biomarker.

Breast Carcinoma: Correlation of Molecular Subtypes with Histopathologic Characteristics

Context: Breast carcinoma is a heterogenous disease and similar histological subtypes may exhibit different behavior and treatment response. The molecular classification may provide better prognostic, predictive and therapeutic information than histological classification. The study aimed at evaluating the distribution of molecular subtypes of breast cancer and its association with prognostic factors. Method: This prospective cross-sectional study was conducted on breast cancer cases, over a period of 2 years, at M.S. Ramaiah Medical College and Hospitals, Bengaluru. The resection specimens were evaluated for histopathological features. Immunohistochemical analysis for ER, PR, Her2neu and Ki-67 expression was performed to identify molecular subtypes. Correlation of molecular subtypes with histopathological prognostic factors was done by Chi- square test or Fischer’s exact test. Results: A total of 85 cases were evaluated and classified into Luminal A (50.6%), Basal like (27%), Luminal B (11.8%) and HER-2 enriched (10.6%) molecular subtypes. Invasive ductal carcinoma was the commonest histologic type across all the molecular subtypes. Majority of low-grade tumors were Luminal A and most of high-grade tumors were Basal like (p= 0.004). HER-2 enriched and Basal like tumors were relatively more frequent in ≤ 50 years of age and Luminal A tumors exhibited less frequent lymph node metastasis. However, these associations fell short of statistical significance. Conclusion: Luminal A tumors are the most common molecular subtype. Statistically significant correlation exists between histologic grade and molecular subtype. There is no significant correlation between molecular subtype and age, tumor size, nodal metastasis, pathological T stage and TNM stage. Keywords: Basal like, Breast carcinoma, HER2­Enriched, Luminal A, Luminal­ B, Molecular subtypes

BREAST CANCER SUBTYPES IN PAKISTANI POPULATION: DATA FROM A SINGLE CENTER

Breast cancer is a complex disease that includes different types of tumors. These tumors can vary in their characteristics, such as the levels of estrogen, progesterone, and HER2/neu receptors. These differences can impact how the tumors respond to treatment, progress, and change over time. The study conducted at the Department of Oncology, Jinnah Hospital, Lahore, from May to November 2019, was a cross-sectional study that involved 90 female patients with breast cancer aged 25 to 75. The researchers analyzed the tumor samples using immunohistochemistry to evaluate ER, PR, and HER2neu levels. FISH was used to evaluate models that had equivocal HER2 by IHC. The participants in this study were 25 to 75 years old, with an average age of 47.10 ± 11.55 years. The average duration of the disease before presenting to the hospital was 6.71 ± 2.63 months. The study found that 74.44% of the female patients had tumors that were ER-positive, 56.67% had tumors that were PR-positive, and 20.0% had tumors that were HER2neu-positive. In conclusion, this study showed that the frequency of positive expression of estrogen, progesterone, and HER2neu in breast cancer patients in this population was consistent with international rates. However, more extensive studies are necessary to determine the exact prevalence of these tumors.

Expression of Her2-Neu in Primary Gastric and Gastroesophageal Adenocarcinoma: An Experience from a Tertiary Center in South India

Gastric cancer is one of the most commonly occurring cancers worldwide, often presenting at an advanced stage. Combining targeted therapy with chemotherapeutic agents can enhance and extend the survival of these patients. This 4-year retrospective study aims to assess the prognostic role of Her2-Neu expression in gastric and gastroesophageal (GE) cancer. Clinicopathological features, histological type (Lauren classification) of adenocarcinoma, and Her2 immunohistochemical expression were correlated with disease-free and overall survival in 114 patients. A Her2 score of 0 and 1+ indicated negativity, while 3+ marked positivity. For cases with a 2+ score, fluorescent in situ hybridization (FISH) was conducted for definitive categorization. Statistical analysis employed IBM SPSS version 20.0 software. Among 114 patients, 13 displayed strong Her2-Neu immunopositivity (3 + ), 9 scored 2 + , and 92 were negative (0 [89] and 1+ [3]). FISH classified 4 and 5 cases as positive and negative, respectively. Most (64.7%) Her2-Neu-positive tumors occurred in the proximal stomach/GE junction (GEJ) and exhibited intestinal morphology (94.1%) with moderate differentiation (p-value &lt; 0.05). Notably, 76.5% of Her2-Neu-positive patients exhibited advanced-stage disease with nodal/distant metastasis. The average disease-free survival was 15.4 months (standard error: 3.55) for positive Her2-Neu expression and 22.07 months (standard error: 1.364) for negative expression. The mean overall survival was 21.14 months (standard error: 3.702) for positive expression and 23.91 months (standard error: 1.474) for negative expression. Her2-Neu expression in gastric/GEJ adenocarcinomas correlates with reduced survival. Evaluating Her2-Neu in proximal gastric/GEJ cancers displaying low-grade intestinal morphology serves as both a predictive and prognostic indicator.

Clinicopathological Significance and Prognostic Role of Her2neu Protein Expression in Patients with Carcinoma Stomach: A Prospective Study from Northern India

Background and Aims Gastric cancer is the third most common cause of cancer-related mortality worldwide after lungs and colorectum. Although controversial, Her2neu overexpression by immunohistochemistry is usually associated with poor prognosis in patients with carcinoma stomach. We conducted a prospective study to evaluate the prognostic role of Her2neu and its correlation with clinical, pathologic type, and stage of the disease. Methods A prospective study was performed on paraffin blocks of 111 gastric cancer specimens (88 patients were biopsy specimens and 23 were gastrectomy specimens). The paraffin blocks were processed for Her2neu receptor immunohistochemical staining and fluorescence in situ hybridization, and scoring was done. Results Her2neu overexpression was detected in 30 out of 111 (27%) patients. The mean age was 57.68 ± 12.82 years, with males constituting two-thirds of total patients. Tobacco addiction was found in 44% of the patients and smoking in 33% of the patients. Her2neu expression was similar in Lauren's intestinal and diffuse histologic type; however, proximal gastric tumors overexpressed Her2neu as compared with distal tumors. Her2neu 2+ or 3 + (odds ratio: 2.52, 95% CI: 1.61–3.95, p = 0.001) was the only independent predictor of survival in gastric cancer patients. Kaplan–Meir survival analysis showed that the survival of gastric cancer patients with Her2neu overexpression (Her2neu 2+ or 3 + ) was significantly lower than that of those with Her2neu nonexpression (p = 0.001). Conclusion Her2neu positivity was a significant predictor of mortality in patients with carcinoma stomach, and Her2neu overexpression was associated with a lower overall survival rate compared with Her2neu nonexpression.

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.

Expression of PD-1 and PD-L1 in Breast Carcinoma: Research Protocol for a Cohort Study

Introduction: Breast cancer is the most common malignant tumour and the leading cause of cancer-related death in women is breast cancer. The Immunohistochemistry (IHC) method utilised antigens and antibodies to interact to identify cellular or tissue constituents (antigens). This research has been employed as a diagnostic tool for specific cancers. When Programmed Cell Death Ligand 1 (PD-L1) binds to Programmed Cell Death 1 (PD-1), it suppresses the cellular immune response by killing and depleting T-cells. Monoclonal antibodies that block the PD-1/ PD-L1 pathway have shown promise as a treatment strategy currently being tested in human cancer trials. Need for the study: Breast cancer is a global issue, and PDL1 expression is emerging as a promising biomarker for breast cancer prognosis. It can provide valuable information treatment planning. Aim: The current study aims to examine the expression of PD-1 and PD-L1 in breast cancer using IHC in all subgroups of breast cancer patients. Both tests can serve as a biomarkers to guide immunotherapeutic interventions, improving prognosis, and correlating with other clinicopathological individual parameters such as age, tumour size, distant metastasis, lymph node involvement, Estrogen Receptor (ER) and Progesterone Receptor (PR) status, Her2neu expression, histological type, and TNM stage. Materials and Methods: This will be a two-year cohort study conducted in the Department of Pathology, Jawaharlal Nehru Medical College (JNMC), Maharashtra, India. The study will include 70 specimens from all cases with a histopathological diagnosis of breast cancer. The Nottingham variant of the Bloom-Richardson Grading System will be used to determine the histological grade of the tumour, and immunostaining for PD-1 and PD-L1 will be performed to evaluate their protein expression.

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.

MALE BREAST CANCER TREATMENT: A CLINICAL CASE*

Relevance: Male breast cancer (BC) has always been behind female BC in detection, treatment, and surveillance. Lower BC frequency in men limits the usefulness of screening. However, BC incidence in men is growing.&#x0D; This paper demonstrate the results of surgical treatment and typical changes in clinical and morphological manifestations of male breast cancer under chemotherapy and surgery.&#x0D; Methods: The article describes a clinical case of a male patient diagnosed with “Cancer of the right breast St III (T4NxM0), edematous-infiltrative form with an intraductal component, upper outer localization. Immunohistochemically luminal subtype B without Her2neu expression”; the condition – after six neoadjuvant chemotherapy courses.&#x0D; Results: Ultrasonography of the mammary glands conducted after six preoperative courses of chemotherapy showed a hypoechoic formation, centralized, with fuzzy, uneven contours, 52.5×48.2×46.1 mm in size, V=60.98 cm3. Compared to March 2022 (the presence of a formation in the right breast craniolateral quadrant, with precise uneven contours, 9.0 cm in size, with infiltrating growth), the tumor formation decreased to US BI-RADS R6, L2. The multidisciplinary council prescribed surgery to the extent of radical mastectomy by Madden on the right and simple mastectomy on the left. The surgery was performed in August 2022. According to a postoperative histological conclusion, the therapeutic pathomorphism was index RCB-2.233, class RCB-II.&#x0D; Conclusion: This article shares the results of systemic and surgical treatment of a man with breast cancer. Considering the clinical picture and anamnesis, literature data, and the clinical protocol, the multidisciplinary group recommended radiation therapy with adjuvant endocrine therapy with tamoxifen for an initial period of five years.&#x0D; * clinical case, male breast cancer (BC), luminal subtype B without Her2neu expression, mastectomy, therapeutic pathomorphism, radiation therapy, endocrine therapy.

MALE BREAST CANCER TREATMENT: A CLINICAL CASE*

Relevance: Male breast cancer (BC) has always been behind female BC in detection, treatment, and surveillance. Lower BC frequency in men&#x0D; limits the usefulness of screening. However, BC incidence in men is growing.&#x0D; This paper demonstrates the results of surgical treatment and typical changes in clinical and morphological manifestations of male breast&#x0D; cancer under chemotherapy and surgery.&#x0D; Methods: The article describes a clinical case of a male patient diagnosed with “Cancer in the right breast St III (T4NxM0), edematousinfiltrative form with an intraductal component, upper outer localization. Immunohistochemically luminal subtype B without Her2neu expression”;&#x0D; the condition – after six neoadjuvant chemotherapy courses.&#x0D; Results: Ultrasonography of the mammary glands conducted after six preoperative courses of chemotherapy showed a hypoechoic formation,&#x0D; centralized, with fuzzy, uneven contours, 52.5×48.2×46.1 mm in size, V=60.98 cm3&#x0D; . Compared to March 2022 (the presence of a formation in&#x0D; the right breast craniolateral quadrant, with precise uneven contours, 9.0 cm in size, with infiltrating growth), the tumor formation decreased to&#x0D; US BI-RADS R6, L2. The multidisciplinary council prescribed surgery to the extent of radical mastectomy by Madden on the right and simple&#x0D; mastectomy on the left. The surgery was performed in August 2022. According to a postoperative histological conclusion, the therapeutic pathomorphism was index RCB-2.233, class RCB-II.&#x0D; Conclusion: This article shares the results of systemic and surgical treatment of a man with breast cancer. Considering the clinical picture and&#x0D; anamnesis, literature data, and the clinical protocol, the multidisciplinary group recommended radiation therapy with adjuvant endocrine therapy&#x0D; with tamoxifen for an initial period of five years.

MALE BREAST CANCER TREATMENT: A CLINICAL CASE*

Relevance: Male breast cancer (BC) has always been behind female BC in detection, treatment, and surveillance. Lower BC frequency in men&#x0D; limits the usefulness of screening. However, BC incidence in men is growing.&#x0D; This paper demonstrates the results of surgical treatment and typical changes in clinical and morphological manifestations of male breast&#x0D; cancer under chemotherapy and surgery.&#x0D; Methods: The article describes a clinical case of a male patient diagnosed with “Cancer in the right breast St III (T4NxM0), edematousinfiltrative form with an intraductal component, upper outer localization. Immunohistochemically luminal subtype B without Her2neu expression”;&#x0D; the condition – after six neoadjuvant chemotherapy courses.&#x0D; Results: Ultrasonography of the mammary glands conducted after six preoperative courses of chemotherapy showed a hypoechoic formation,&#x0D; centralized, with fuzzy, uneven contours, 52.5×48.2×46.1 mm in size, V=60.98 cm3&#x0D; . Compared to March 2022 (the presence of a formation in&#x0D; the right breast craniolateral quadrant, with precise uneven contours, 9.0 cm in size, with infiltrating growth), the tumor formation decreased to&#x0D; US BI-RADS R6, L2. The multidisciplinary council prescribed surgery to the extent of radical mastectomy by Madden on the right and simple&#x0D; mastectomy on the left. The surgery was performed in August 2022. According to a postoperative histological conclusion, the therapeutic pathomorphism was index RCB-2.233, class RCB-II.&#x0D; Conclusion: This article shares the results of systemic and surgical treatment of a man with breast cancer. Considering the clinical picture and&#x0D; anamnesis, literature data, and the clinical protocol, the multidisciplinary group recommended radiation therapy with adjuvant endocrine therapy&#x0D; with tamoxifen for an initial period of five years.