Gastric cancer and gastroesophageal junction cancer represent the leading cause of tumor-related death worldwide. Although advances in immunotherapy and molecular targeted therapy have expanded treatment options, they have not significantly altered the prognosis for patients with unresectable or metastatic gastric cancer. A minority of patients, particularly those with PD-L1-positive, HER-2-positive, or MSI-high tumors, may benefit more from immune checkpoint inhibitors and/or HER-2-directed therapies in advanced stages. However, for those lacking specific targets and unique molecular features, conventional chemotherapy remains the only recommended effective and durable regimen. In this review, we summarize the roles of various signaling pathways and further investigate the available targets. Then, the current results of phase II/III clinical trials in advanced gastric cancer, along with the superiorities and limitations of the existing biomarkers, are specifically discussed. Finally, we will offer our insights in precision treatment pattern when encountering the substantial challenges.

This study systematically reviewed the role of diffusion-weighted imaging (DWI) in the assessment of molecular prognostic biomarkers in breast cancer, focusing on the correlation of apparent diffusion coefficient (ADC) with hormone receptor status and prognostic biomarkers. Our meta-analysis includes data from 52 studies examining ADC values in relation to estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), and Ki-67 status. The results indicated significant differences in ADC values among different receptor statuses, with ER-positive, PgR-positive, HER2-negative, and Ki-67-positive tumors having lower ADC values compared to their negative counterparts. This study also highlights the potential of advanced DWI techniques such as intravoxel incoherent motion and non-Gaussian DWI to provide additional insights beyond ADC. Despite these promising findings, the high heterogeneity among the studies underscores the need for standardized DWI protocols to improve their clinical utility in breast cancer management.

Biomarkers such as hormone receptors (HR) and human epidermal growth factor receptor2 (HER2) may change after neoadjuvant chemotherapy (NAC) in breast cancer patients. The aim of this study was to investigate the rates of receptor change after NAC and to evaluate the prognostic impact of change. Patients with breast cancer who received NAC were included in the study. Changes in pathological findings (ER, PR, HER-2, Ki-67, grade) before and after NAC were examined. In addition, the effect of receptor exchange on prognosis was evaluated. Kaplan Meier analysis was used for survival analyses. Study was approved by Ethics Board of Tepecik Training and Research Hospital (Decision number 2021/10-02). We confirm that all methods were performed in accordance with relevant named guidelines and regulations. The study included 203 female patients. When pathological findings before and after NAC were compared, significant regression was found in grade and Ki-67 values (p = 0.003, p < 0.001). ER change rate was 11.8%, PR change rate was 24.6% and HER-2 change rate was 12.5%. No significant correlation was found between ER, PR and HER-2 changes and prognosis. The pathological T stage after NAC being 1 or 2, no lymph nodes detected, and the tumor grade being 1 or 2 were independent variables related to survival (p: 0.002, p: 0.014, p < 0.001). In patients with breast cancer, it would be appropriate to re-evaluate the HER-2 and HR status of the surgical specimen following NAC, especially in initially negative patients. The correlation of receptor discordance with prognosis is not clear and more extensive studies are needed.

Canine melanoma is a malignant and aggressive neoplasm showing clinical, histological, and molecular features similar to the human counterpart. In human medicine, epidermal growth factor receptors (EGFRs) have already been suggested as prognostic markers and potential therapeutic targets in cutaneous melanoma. The aim of this study was to evaluate the expression of HER-2 and HER-3 in canine melanomas by immunohistochemistry and correlate their expression to the clinicopathological parameters of the examined tumors. Thirty-seven canine melanoma samples were recruited. Data regarding signalment and clinical parameters were also collected. The population was composed of 18 cutaneous, 16 oral/mucosal, and three digital/foot pad melanomas. Histopathological investigations were carried out to analyze histological type, ulceration, and mitotic count. On each sample, immunohistochemistry was performed using an anti-Melan-A or anti-Melanoma antigen, i.e., anti-HER-2 and anti-HER-3 antibodies. HER-2 and HER-3 positivity were classified using already established scoring criteria and a statistical analysis was carried out. The results highlighted that HER-2 expression was observed in 48.6% of the samples and HER-3 expression in 18.9%. The highest HER 2 score (3+) was recorded in 16.2% of the samples, while the coexpression of the two receptors was detected in 13.5% of the samples. A statistically significant association (p < 0.05) was observed between the expression of HER-2 and HER-3 and the presence of ulceration in oromucosal tumors. This work confirms the expression of HER-2 and HER-3 in canine melanomas and suggests a putative association with negative prognostic parameters. Further studies are necessary to strengthen these data by increasing the samples size and combining pathological examinations with molecular biology in the investigation of EGFR family receptors.

UNASSIGNED: To explore the application of multiparametric MRI-based radiomic nomogram for assessing HER-2 2+ status of breast cancer (BC).
UNASSIGNED: Patients with pathology-proven HER-2 2+ invasive BC, who underwent preoperative MRI were divided into training (72 patients, 21 HER-2-positive and 51 HER-2-negative) and validation (32 patients, 9 HER-2-positive and 23 HER-2-negative) sets by randomization. All were classified as HER-2 2+ FISH-positive (HER-2-positive) or -negative (HER-2-negative) according to IHC and FISH. The 3D VOI was drawn on MR images by two radiologists. ADC, T2WI, and DCE images were analyzed separately to extract features (n = 1906). L1 regularization, F-test, and other methods were used to reduce dimensionality. Binary radiomics prediction models using features from single or combined imaging sequences were constructed using logistic regression (LR) classifier then and validated on a validation dataset. To build a radiomics nomogram, multivariate LR analysis was conducted to identify independent indicators. An evaluation of the model\'s predictive efficacy was made using AUC.
UNASSIGNED: On the basis of combined ADC, T2WI, and DCE images, ten radiomic features were extracted following feature dimensionality reduction. There was superior diagnostic efficiency of radiomic signature using all three sequences compared to either one or two sequences (AUC for training group: 0.883; AUC for validation group: 0.816). Based on multivariate LR analysis, radiomic signature and peritumoral edema were independent predictors for identifying HER-2 2 +. In both training and validation datasets, nomograms combining peritumoral edema and radiomics signature demonstrated an effective discrimination (AUCs were respectively 0.966 and 0. 884).
UNASSIGNED: The nomogram that incorporated peritumoral edema and multiparametric MRI-based radiomic signature can be used to effectively predict the HER-2 2+ status of BC.

UNASSIGNED: Breast cancer is a complex disease with variability in clinical manifestation, response to current therapy, and biochemical and histological features among various subgroups. Histologic grading and immuno-histochemical evaluation of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), and Ki-67 proliferation index play a crucial role in increasing the differential diagnostic value among various types of breast carcinoma. The aim of this study was to determine the histopathological and immuno-histochemical characteristics of breast tumors from a University Laboratory of Pathology in Greece.
UNASSIGNED: The study included female patients over 18 years of age, whose histopathological and immunohistochemical reports were stored in the archives of the First Department of Pathology of National and Kapodistrian University of Athens. The study involved 197 female patients with a median age of 70 years and median tumor size of 2.6 cm.
UNASSIGNED: Most tumors were located at the left breast and ductal carcinoma was the most common histologic type (35.5%). Most tumors had histologic grade 2 (106, 53.8%), and were classified as TNM stage IIA (65, 33%). Most grade 1 and 2 tumors exhibited high expression of PR, whereas most grade 3 tumors had no PR expression. Moreover, patients with triple-negative cancer presented with grades 2 and 3 at a lower percentage compared to patients without a triple-negative phenotype (p=0.001).
UNASSIGNED: The study provided valuable insights into the histopathological and immuno-histochemical characteristics involved in the development and progression of breast cancer.

As an important prognostic indicator in breast cancer, human epithelial growth factor receptor-2 (HER-2) is of importance for assessing prognosis of breast cancer patients, whose accurate and facile analysis are imperative in clinical diagnosis and treatment. Herein, photoactive Z-scheme UiO-66/CdIn2S4 heterojunction was constructed by a hydrothermal method, whose optical property and photoactivity were critically investigated by a range of techniques, combined by elucidating the interfacial charge transfer mechanism. Meanwhile, PtPdCu nanoflowers (NFs) were fabricated by a simple aqueous wet-chemical method, whose peroxidase (POD)-mimicking catalytic activity was scrutinized by representative tetramethylbenzidine (TMB) oxidation in H2O2 system. Taken together, the UiO-66/CdIn2S4 based photoelectrochemical (PEC) aptasensor was established for quantitative analysis of HER-2, where the detection signals were further magnified through catalytic precipitation reaction towards 4-chloro-1-naphthol (4-CN) oxidation (assisted by the PtPdCu NFs nanozyme). The PEC aptasensor presented a broader linear range within 0.1 pg mL-1-0.1 μg mL-1 and a lower limit of detection of 0.07 pg mL-1. This work developed a new PEC aptasensor for ultrasensitive determination of HER-2, holding substantial promise for clinical diagnostics.

The APIS Breast Cancer Subtyping Kit is an mRNA-based assessment of the seven parameters including three biomarkers routinely assessed in all the newly diagnosed breast cancers (BC), oestrogen receptor (ER), progesterone receptor (PR) and HER-2 and an additional four genes that create a novel proliferation signature, MKI67, PCNA, CCNA2 and KIF23. Taken together, the data are used to produce a molecular subtype for every sample. The kit was evaluated against the current standard protocol of immunohistochemistry (IHC) and/or in situ hybridisation (ISH) in breast cancer patients. The data were presented at the weekly breast multidisciplinary team (MDT) meeting. A total of 98 consecutive cases of pre-operative breast cancer core biopsies and two core biopsies of nodal metastases yielding 100 cases were assessed. IHC and APIS results were available for 100 and 99 cases. ER was concordant in 97% cases, PR was concordant in 89% and HER-2 results were concordant with IHC/ISH in 100% of the cases. Ki-67 IHC was discordant in 3% of cases when compared with MK167 alone but discordant in 24% when compared with the four-gene proliferation signature. In conclusion, our study indicates that the APIS Breast Cancer Subtyping Kit is highly concordant when compared to the results produced for ER/PR/HER-2 by IHC and/or ISH. The assay could play a role in the routine assessment of newly diagnosed breast cancer (BC) specimens.

The aim of the study was to investigate the expression of EGFR and HER-2 oncogenes using an experimental two stage chemically induced carcinogenesis protocol on the dorsal skin in FVB/N mice. Forty female FVB/N mice 4 weeks old, were grouped into one control (n = 8) and two experimental groups (Group A: n = 16, Group B: n = 16) following a randomization process. Two-stage carcinogenesis protocol, was implicated, including an initial treatment with 97.4 nmol DMBA on their shaved dorsal skin and subsequent treatments of 32.4 nmol TPA applications after 13 weeks for Group A and after 20 weeks for Group B. The control group C, received no treatment. Skin was examined weekly for tumor development. Post-experiment, animals were euthanized for tissue analysis. The histological status of the skin lesions in the experimental groups corresponded well with tumour advancement (from dysplasia to poorly-differentiated carcinoma). Tumour sections were evaluated histologically and immunohistochemically. EGFR expression was found significantly higher in precancerous and malignant tumours (p = 042 and p = 008 respectively), while tended to be higher in benign tumours (p = 079), compared to normal histology. Moreover, mean percentage of EGFR positive expression in malignant tumours was significantly higher than in benign tumours (p < 001). HER-2 expression was found significantly higher in precancerous and malignant tumours (p = 042 and p = 015 respectively), while tended to be higher in benign tumours (p = 085), compared to normal histology. Furthermore, mean percentage of HER-2 positive expression in malignant tumours was significantly higher than in benign tumours (p = 005). The study demonstrated that in FVB/N mice subjected to a two-stage chemically induced carcinogenesis protocol, there was a significant increase in the expression of EGFR and HER-2 oncogenes in precancerous and malignant skin lesions compared to normal tissue. This suggests a potentially early role of these oncogenes in the progression of skin tumours in this model.

Over the past 20 years, there has been a paradigm shift in the care of patients with non-small cell lung cancer (NSCLC), who now have a range of systemic treatment options including targeted therapy, chemotherapy, immunotherapy (ICI), and antibody-drug conjugates (ADCs). A proportion of these cancers have single identifiable alterations in oncogenes that drive their proliferation and cancer progression, known as \"oncogene-addiction\". These \"driver alterations\" are identified in approximately two thirds of patients with lung adenocarcinomas, via next generation sequencing or other orthogonal tests. It was noted in the early clinical development of ICIs that patients with oncogene-addicted NSCLC may have differential responses to ICI. The toxicity signal for patients with oncogene-addicted NSCLC when treated with ICIs also seemed to differ depending on the alteration present and the specific targeted agent used. Developing a greater understanding of the underlying reasons for these clinical observations has become an important area of research in NSCLC. In this review, we analyze the efficacy and safety of ICI according to specific mutations, and consider possible future directions to mitigate safety concerns and improve the outcomes for patients with oncogene-addicted NSCLC.