Clinicopathologic Features and Digital Imaging Analysis of HER2 Protein in Breast Carcinomas With Different HER2 Fluorescence in Situ Hybridization Patterns.

Background: HER2-targeted therapies have significantly improved outcomes for patients with HER2-positive breast cancer (BC), which represents 15% to 20% of all BC cases. HER2 status is assessed via immunohistochemistry (IHC) and/or in situ hybridization (ISH), dividing BCs into five groups (G1-G5).

Patients And Methods: In a study of 2,702 primary BC cases, comprising 12.

ALDH1A1 promotes PARP inhibitor resistance by enhancing retinoic acid receptor-mediated DNA polymerase θ expression.

Poly (ADP-ribose) Polymerase (PARP) inhibitors (PARPi) have been approved for both frontline and recurrent setting in ovarian cancer with homologous recombination (HR) repair deficiency. However, more than 40% of BRCA1/2-mutated ovarian cancer lack the initial response to PARPi treatment, and the majority of those that initially respond eventually develop resistance. Our previous study has demonstrated that increased expression of aldehyde dehydrogenase 1A1 (ALDH1A1) contributes to PARPi resistance in BRCA2-mutated ovarian cancer cells by enhancing microhomology-mediated end joining (MMEJ) but the mechanism remains unknown.

NSD1 deposits histone H3 lysine 36 dimethylation to pattern non-CG DNA methylation in neurons.

During postnatal development, the DNA methyltransferase DNMT3A deposits high levels of non-CG cytosine methylation in neurons. This methylation is critical for transcriptional regulation, and loss of this mark is implicated in DNMT3A-associated neurodevelopmental disorders (NDDs). Here, we show in mice that genome topology and gene expression converge to shape histone H3 lysine 36 dimethylation (H3K36me2) profiles, which in turn recruit DNMT3A and pattern neuronal non-CG methylation.

A Validation Study of Human Epidermal Growth Factor Receptor 2 Immunohistochemistry Digital Imaging Analysis and its Correlation with Human Epidermal Growth Factor Receptor 2 Fluorescence Hybridization Results in Breast Carcinoma.

Background: The Visiopharm human epidermal growth factor receptor 2 (HER2) digital imaging analysis (DIA) algorithm assesses digitized HER2 immunohistochemistry (IHC) by measuring cell membrane connectivity. We aimed to validate this algorithm for clinical use by comparing with pathologists' scoring and correlating with HER2 fluorescence hybridization (FISH) results.

Materials And Methods: The study cohort consisted of 612 consecutive invasive breast carcinoma specimens including 395 biopsies and 217 resections.

Quantitative digital imaging analysis of HER2 immunohistochemistry predicts the response to anti-HER2 neoadjuvant chemotherapy in HER2-positive breast carcinoma.

Purpose: Patients with HER2-positive breast cancer commonly receive anti-HER2 neoadjuvant chemotherapy and pathologic complete response (pCR) can be achieved in up to half of the patients. HER2 protein expression detected by immunohistochemistry (IHC) can be quantified using digital imaging analysis (DIA) as a value of membranous connectivity. We aimed to investigate the association HER2 IHC DIA quantitative results with response to anti-HER2 neoadjuvant chemotherapy.