her2 overexpression
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2022 ◽  
Vol 8 (1) ◽  
pp. 368-378
Author(s):  
Nabir Hossain

Background: Gastric cancer is the fourth commonest cancer worldwide. It is also recognized as the second commonest cause of cancer related death in the global perspective. Although the incidence of gastric cancer has gradually decreased over the last half of the century, it varies among the different part of the world and different ethnic group. Mortality from gastric cancer extremely high, and it is second only to lung cancer. Gastric cancer occurs more frequently in men than in women. Aim of the study: Aim of the study was to find the clinic-profile outcome HER2 Positive Gastric and Gastroesophageal Adenocarcinoma.Methods:This cross sectional study was conducted in the Department of Surgical Oncology of National Institute of Cancer, Research and Hospital, Mohakhali, Dhaka. The study period was from March, 2014 to April, 2015. A total of 80 patients were included for the study. After receiving the gastrectomy specimen, it was fixed in 10% formaldehyde. Data were compiled and necessary statistical analysis were carried out using computer based software package for social science (SPSS 16.1). Ethical clearance was taken from the ethical committee of NICRH.Results:The highest patients were from 61-70 years’ age group and the lowest were from 71-80 years. The mean age of the patients was 59.71 (±10.19) years. The female to male ratio in this study was 1: 2.48. 66 (82.5%) patients were presented with anemia which was followed by 39 (48.75%) cases with dehydration. Most of the tumors were located in the distal part of the stomach (11.67%). Regarding staging 79(12.65%) patients were in the advanced stage of the disease. The correlation between HER2 overexpression and TNM staging has been tabulated below where it is shown that only Nodal (N) staging has the significant correlation with the HER2 overexpression.Conclusion:It is already mentioned that, in early history of immunohistochemistry, HER2 overexpression in case of carcinoma stomach was highly varied in different studies (from 9-92%). But recently, it was found around 9-32%, in several studies all over the world. It is necessary to conduct further studies with larger samples and long term follow-up in order to draw definite conclusions regarding the role of HER2/neu overexpression.


2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Shingo Maeda ◽  
Kosei Sakai ◽  
Kenjiro Kaji ◽  
Aki Iio ◽  
Maho Nakazawa ◽  
...  

AbstractEpidermal growth factor receptors 1 and 2 (EGFR and HER2) are frequently overexpressed in various malignancies. Lapatinib is a dual tyrosine kinase inhibitor that inhibits both EGFR and HER2. Although a phase III trial failed to show the survival benefits of lapatinib treatment after first-line chemotherapy in patients with EGFR/HER2-positive metastatic urothelial carcinoma, the efficacy of lapatinib for untreated urothelial carcinoma is not well defined. Here, we describe the therapeutic efficacy of lapatinib as a first-line treatment in a canine model of muscle-invasive urothelial carcinoma. In this non-randomized clinical trial, we compared 44 dogs with naturally occurring urothelial carcinoma who received lapatinib and piroxicam, with 42 age-, sex-, and tumor stage-matched dogs that received piroxicam alone. Compared to the dogs treated with piroxicam alone, those administered the lapatinib/piroxicam treatment had a greater reduction in the size of the primary tumor and improved survival. Exploratory analyses showed that HER2 overexpression was associated with response and survival in dogs treated with lapatinib. Our study suggests that lapatinib showed encouraging durable response rates, survival, and tolerability, supporting its therapeutic use for untreated advanced urothelial carcinoma in dogs. The use of lapatinib as a first-line treatment may be investigated further in human patients with urothelial carcinoma.


2022 ◽  
Vol 29 (1) ◽  
pp. 9-23
Author(s):  
Zaleha Kamaludin ◽  
Alaa Siddig ◽  
Najib Majdi Yaacob ◽  
Alfred K. Lam ◽  
Wan Faiziah Wan Abdul Rahman

Biomarker identification is imperative for invasive breast carcinoma, which is more aggressive and associated with higher mortality and worse prognosis in younger patients (<45 years) than in older patients (>50 years). The current study aimed to investigate angiopoietin-like protein 4 (ANGPTL4) and insulin-like growth factor-1 (IGF-1) protein expression in breast tissue from young patients with breast carcinoma. Immunohistochemical staining was applied in formalin-fixed, paraffin-embedded samples of breast carcinoma tissue from young patients aged <45 years at the time of diagnosis. Both proteins were expressed in the majority of cases. The highest frequency of positive ANGPTL4 and IGF-1 expression was observed in the luminal A subtype, whereas the HER2-overexpression subtype exhibited the lowest expression frequency for both proteins. There was no significant association between ANGPTL4 (p = 0.897) and IGF-1 (p = 0.091) expression and molecular subtypes of breast carcinoma. The histological grade was a significant predictor of ANGPTL4 expression (grade 1 vs. grade 3, adjusted odds ratio = 12.39, p = 0.040). Therefore, ANGPTL-4 and IGF-1 expressions are common in young breast carcinoma tissue. There is a potential use of them as biomarkers in breast carcinoma.


Author(s):  
Fengjiao Chen ◽  
Hui Jing ◽  
Haitao Shang ◽  
Haoyan Tan ◽  
Haobo Yang ◽  
...  

IntroductionTo explore the diagnostic value of combining superb microvascular imaging (SMI), shear-wave elastography (SWE), and Breast Imaging Reporting and Data System (BI-RADS) to distinguish different molecular subtypes of invasive ductal carcinoma (IDC).Material and methodsA total of 239 surgically confirmed IDC masses in 201 patients underwent conventional ultrasound, SMI, and SWE examination, the information such as echo pattern, posterior features, margins, SMI pixels, and hardness of the masses was recorded. According to the St. Gallen standard, breast masses were classified as Luminal A, Luminal B, HER2 overexpression, and triple-negative subtype. We further explored the differences between different molecular subtypes of IDC.ResultsLuminal A subtype had the following characteristics: low histologic grade, posterior acoustic shadowing (p= 0.019), spiculated margins (p<0.001) , and relatively soft. Luminal B subtype was characterized by low histological grade (p <0.0001), posterior acoustic shadowing or indifference, and indistinct margins. HER2 overexpression breast cancers were characterized by high histological grade, enhanced posterior acoustics or indifference, calcifications (p= 0.005), spiculated or indistinct margins, vascularity (p=0.005), and relative stiffness. Triple-negative breast cancers had the characteristics of high histological grade, posterior echogenic enhancement, lack of calcifications, circumscribed or microlobulated margins, low blood flow signals, and stiff tissue (p=0.013).ConclusionsOur study demonstrated the significant differences and trends among the IDC four subtypes by the combined application of SMI, SWE, and BI-RADS lexicon, which are of great significance for early diagnosis, selection of treatment methods, and evaluation of prognosis of IDC.


2022 ◽  
Author(s):  
Meng Luo ◽  
Huihui Chen ◽  
Hao Deng ◽  
Yao Jin ◽  
Gui Wang ◽  
...  

Abstract PurposePostmastectomy radiotherapy (PMRT) after NAC in breast cancer patients with initial clinical stage cT1−2N+, especially for those who achieved ypT1−2N0, is still controversial. This study was to evaluate the survival prognosis of cT1−2N+ patients after NAC with or without PMRT, and to discuss the selection of patients who may omit PMRT.Patients and MethodsFrom January 2005 to December 2017, 3055 female breast cancer patients underwent mastectomy in our medical center, among whom 215 patients of cT1−2N+ stage, receiving neoadjuvant chemotherapy (NAC) with or without PMRT were finally analyzed. The median follow-up duration was 72.6 months. The primary endpoint was overall survival, and the secondary endpoint was disease-free survival. Comparison was conducted between PMRT and non-PMRT subgroups.ResultsOf the 215 eligible patients, 35.8% (77/215) cT1−2N+ patients achieved ypT0−2N0 after NAC while 64.2% (138/215) of the patients remained nodal positive (ypT0−2N+). The 5-year DFS of ypT0−2N0 non-PMRT was 79.5% (95% confidence interval [CI] 63.4-95.6%). No statistically significant difference was observed between the ypT0−2N0 PMRT and non-PMRT subgroups for the 5-year DFS (78.5% vs 79.5%, p = 0.673) and OS (88.8% vs 90.8%, p = 0.721). The 5-years DFS didn’t obviously differ between the ypT0−2N0 non-PMRT subgroup and cT1−2N0 subgroup (79.5% vs 93.3%, p = 0.070). By using Cox regression model in multivariate analyses of prognosis in ypT0−2N+ PMRT subgroup, HER2 overexpression and triple-negative breast cancer were significantly poor predictors of DFS and OS, while ypN stage was significant independent predictors of OS.ConclusionAn excellent response to NAC (ypT0−2N0) indicates a sufficiently favorable prognosis, and PMRT might be omitted for cT1−2N+ breast cancer patients with ypT0−2N0 after NAC.


2021 ◽  
Vol 9 (B) ◽  
pp. 1570-1574
Author(s):  
Imam Hafidh Zaini ◽  
Widyanti Soewoto ◽  
Ida Bagus Budhi

AIM: This study aims to evaluate the effect of adjuvant chemotherapy on estradiol levels in patients with HER 2-overexpression breast cancer in a developing country. METHODS: This comparative study with pre- and post-design model observation approach, involving patients with HER 2-overexpression breast cancer who had undergone surgery and had never received chemotherapy or hormonal therapy before, who were then given adjuvant chemotherapy. Estradiol levels were measured before and after chemotherapy. The study was carried out in the surgical oncology division of RSUD Dr. Moewardi (RSDM) Surakarta from January 2020-December 2020. Descriptive data are presented in a frequency table based on age, menstrual status, parity status, breastfeeding status, contraception, contraception duration, family history, stage, and histological grade. Before and after chemotherapy in patients with breast cancer, the estradiol levels employed the paired sample t-test of the Wilcoxon rank test because the data did not meet the normality assumption. RESULTS: From the total data of 21 patients, 15 patients experienced a decrease in estradiol levels after chemotherapy, while six patients underwent an increase. The mean estradiol level before chemotherapy was 89.41 pg/ml, whereas the mean estradiol level after chemotherapy was 55.90 pg/ml. It indicates a difference in the decrease in estradiol levels of 33.51 pg/ml. The statistical test results also obtained a p-value of = 0.033 (p < 0.05), which signifies a significant difference between estradiol levels before and after chemotherapy. Thus, chemotherapy is effective in lowering estradiol levels in patients with breast cancer. CONCLUSION: Chemotherapy affects decreasing estradiol levels in patients with HER2 overexpression breast cancer.


2021 ◽  
Vol 10 (22) ◽  
pp. 5394
Author(s):  
Magdalena Gumowska ◽  
Joanna Mączewska ◽  
Piotr Prostko ◽  
Katarzyna Roszkowska-Purska ◽  
Katarzyna Dobruch-Sobczak

Molecular profile of breast cancer provides information about its biological activity, prognosis and treatment strategies. The purpose of our study was to investigate the correlation between ultrasound features and molecular subtypes of breast cancer. From June 2019 to December 2019, 86 patients (median age 57 years; range 32–88) with 102 breast cancer tumors were included in the study. The molecular subtypes were classified into five types: luminal A (LA), luminal B without HER2 overexpression (LB HER2−), luminal B with HER2 overexpression (LB HER2+), human epidermal growth factor receptor 2 positive (HER2+) and triple negative breast cancer (TNBC). Histopathological verification was obtained in core biopsy or/and post-surgery specimens in all cases. Univariate logistic regression analysis was performed to assess the association between the subtypes and ultrasound imaging features. Experienced radiologists assessed lesions according to the BIRADS-US lexicon. The ultrasound scans were performed with a Supersonic Aixplorer and Supersonix. Based on histopathological verification, the rates of LA, LB HER2−, LB HER2+, HER2+, and TNBC were 33, 17, 17, 16, 19, respectively. Both LB HER2+ and HER2+ subtypes presented higher incidence of calcification (OR = 3.125, p = 0.02, CI 0.0917–5.87) and HER2+ subtype presented a higher incidence of posterior enhancement (OR = 5.75, p = 0.03, CI 1.2257–32.8005), compared to other subtypes. The calcifications were less common in TNBC (OR = 0.176, p = 0.0041, CI 0.0469–0.5335) compared to other subtypes. There were no differences with regard to margin, shape, orientation, elasticity values and vascularity among five molecular subtypes. Our results suggest that there is a correlation between ultrasonographic features assessed according to BIRADS-US lexicon and BC subtypes with HER2 overexpression (both LB HER2+ and HER2+). It may be useful for identification of these aggressive subtypes of breast cancer.


Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5746
Author(s):  
Nicolas Stoup ◽  
Maxime Liberelle ◽  
Céline Schulz ◽  
Sumeyye Cavdarli ◽  
Romain Vasseur ◽  
...  

The HER2 receptor and its MUC4 mucin partner form an oncogenic complex via an extracellular region of MUC4 encompassing three EGF domains that promotes tumor progression of pancreatic cancer (PC) cells. However, the molecular mechanism of interaction remains poorly understood. Herein, we decipher at the molecular level the role and impact of the MUC4EGF domains in the mediation of the binding affinities with HER2 and the PC cell tumorigenicity. We used an integrative approach combining in vitro bioinformatic, biophysical, biochemical, and biological approaches, as well as an in vivo study on a xenograft model of PC. In this study, we specified the binding mode of MUC4EGF domains with HER2 and demonstrate their “growth factor-like” biological activities in PC cells leading to stimulation of several signaling proteins (mTOR pathway, Akt, and β-catenin) contributing to PC progression. Molecular dynamics simulations of the MUC4EGF/HER2 complexes led to 3D homology models and identification of binding hotspots mediating binding affinity with HER2 and PC cell proliferation. These results will pave the way to the design of potential MUC4/HER2 inhibitors targeting the EGF domains of MUC4. This strategy will represent a new efficient alternative to treat cancers associated with MUC4/HER2 overexpression and HER2-targeted therapy failure as a new adapted treatment to patients.


2021 ◽  
Vol 1 (5) ◽  
pp. 387-392
Author(s):  
YUKI TATEISHI ◽  
YUICHI YAMADA ◽  
TAKEO YAMAMOTO ◽  
TAISUKE SASAKI ◽  
SHINICHIRO KAWATOKO ◽  
...  

Aim: Classically, ‘Paget disease’ refers to a distinct histological pattern in breast carcinoma. Here, we review the clinicopathological features of anorectal adenocarcinoma with ‘pagetoid’ spread. Materials and Methods: Histological and immunohistochemical records for 11 cases of anorectal adenocarcinoma with pagetoid spread among 958 Japanese patients with primary rectal/anal carcinoma were reviewed. Results: Grossly, nine of 11 cases had areas of invasive carcinoma: Tubular adenocarcinoma in eight and neuroendocrine carcinoma in one. Pagetoid components were positive for cytokeratin 7 in eight cases, cytokeratin 20 and caudal type homeobox 2 in all 11 cases, and p63 in one case, but were negative for estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2), gross cystic disease fluid protein-15, and GATA binding protein 3. Conclusion: The prevalence of perianal Paget disease in this series was 1.1%, with two cases of genuine perianal Paget disease with a rectal phenotype without invasive carcinoma. The rectal phenotype of perianal Paget disease may not be associated with HER2 overexpression.


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