Prediction of response to anti-HER2 therapy using a multigene assay.

HER2-positive breast cancer (BC), which constitutes 13-15% of cases, shows variable response to anti-HER2 therapies. HER2-positivity, defined as protein overexpression (immunohistochemistry (IHC) score 3+) or equivocal expression (IHC 2+) with evidence of HER2 gene amplification, determines the eligibility to anti-HER2 therapy. MammaTyper® assay (Cerca Biotech GmbH) is a RT-qPCR BC subtyping platform based on the mRNA expression of ERBB2, ESR1, PGR, and MKI67.

Differential response of HER2-positive breast cancer to anti-HER2 therapy based on HER2 protein expression level.

Background: Increasing data indicate that HER2-positive (HER2 + ) breast cancer (BC) subtypes exhibit differential responses to targeted anti-HER2 therapy. This study aims to investigate these differences and the potential underlying molecular mechanisms.

Methods: A large cohort of BC patients (n = 7390) was utilised.

Digital Technology in Diagnostic Breast Pathology and Immunohistochemistry.

Digital technology has been used in the field of diagnostic breast pathology and immunohistochemistry (IHC) for decades. Examples include automated tissue processing and staining, digital data processing, storing and management, voice recognition systems, and digital technology-based production of antibodies and other IHC reagents. However, the recent application of whole slide imaging technology and artificial intelligence (AI)-based tools has attracted a lot of attention.

Potential quality pitfalls of digitalized whole slide image of breast pathology in routine practice.

Using digitalized whole slide images (WSI) in routine histopathology practice is a revolutionary technology. This study aims to assess the clinical impacts of WSI quality and representation of the corresponding glass slides. 40,160 breast WSIs were examined and compared with their corresponding glass slides.

Spindle cell lesions of the breast: a diagnostic approach.

Spindle cell lesions of the breast comprise a heterogeneous group of lesions, ranging from reactive and benign processes to aggressive malignant tumours. Despite their rarity, they attract the attention of breast pathologists due to their overlapping morphological features and diagnostic challenges, particularly on core needle biopsy (CNB) specimens. Pathologists should recognise the wide range of differential diagnoses and be familiar with the diverse morphological appearances of these lesions to make an accurate diagnosis and to suggest proper management of the patients.

Prognostic significance of heat shock protein 90AA1 (HSP90α) in invasive breast cancer.

Aims: The mechanisms that drive breast cancer (BC) progression and poor outcome are not fully understood. The human heat shock protein 90 alpha family class A member 1 (HSP90α) encoded by the gene has a vital role in cellular responses to stress and is implicated in the development and progression of many cancers. The current study aims to explore the clinical and prognostic importance of HSP90α in BC.

The ITIM-Containing Receptor: Leukocyte-Associated Immunoglobulin-Like Receptor-1 (LAIR-1) Modulates Immune Response and Confers Poor Prognosis in Invasive Breast Carcinoma.

Background: The leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) plays a role in immune response homeostasis, extracellular matrix remodelling and it is overexpressed in many high-grade cancers. This study aimed to elucidate the biological and prognostic role of LAIR-1 in invasive breast cancer (BC).

Methods: The biological and prognostic effect of LAIR-1 was evaluated at the mRNA and protein levels using well-characterised multiple BC cohorts.

The prognostic significance of interferon-stimulated gene 15 (ISG15) in invasive breast cancer.

Background: Lymphovascular invasion (LVI) is a prognostic factor in early-stage invasive breast cancer (BC). Through bioinformatics, data analyses of multiple BC cohorts revealed the positive association between interferon-stimulated gene 15 (ISG15) LVI status. Thus, we explored the prognostic significance of ISG15 in BC.

Elevated MMP9 expression in breast cancer is a predictor of shorter patient survival.

Purpose: MMP9 is a matricellular protein associated with extracellular matrix (ECM) remodelling, that promotes tumour progression, and modulates the activity of cell adhesion molecules and cytokines. This study aims to assess the prognostic value of MMP9 and its association with cytoskeletal modulators in early-stage invasive breast cancer (BC).

Methods: MMP9 expression was evaluated by immunohistochemistry using a well-characterised series of primary BC patients with long-term clinical follow-up.

A novel prognostic two-gene signature for triple negative breast cancer.

The absence of a robust risk stratification tool for triple negative breast cancer (TNBC) underlies imprecise and nonselective treatment of these patients with cytotoxic chemotherapy. This study aimed to interrogate transcriptomes of TNBC resected samples using next generation sequencing to identify novel biomarkers associated with disease outcomes. A subset of cases (n = 112) from a large, well-characterized cohort of primary TNBC (n = 333) were subjected to RNA-sequencing.

The prognostic significance of ALDH1A1 expression in early invasive breast cancer.

Aims: Aldehyde dehydrogenase family 1 member A1 (ALDH1A1) is reportedly a key ALDH isozyme linked to the cancer stem cells (CSC) of many solid tumours, where it is involved in self-renewal, differentiation and self-protection. In this study, the prognostic significance of ALDH1A1 expression in early invasive breast cancer (BC) and its role as a BC stem cell (BCSC) were evaluated.

Methods And Results: ALDH1A1 expression was assessed, using immunohistochemistry and tissue microarrays, in a large well-characterised BC cohort.

New Advances in Molecular Breast Cancer Pathology.

Breast cancer (BC) comprises a diverse spectrum of diseases featuring distinct presentation, morphological, biological, and clinical phenotypes. BC behaviour and response to therapy also vary widely. Current evidence indicates that traditional prognostic and predictive classification systems are insufficient to reflect the biological and clinical heterogeneity of BC.

Artificial intelligence in digital breast pathology: Techniques and applications.

Breast cancer is the most common cancer and second leading cause of cancer-related death worldwide. The mainstay of breast cancer workup is histopathological diagnosis - which guides therapy and prognosis. However, emerging knowledge about the complex nature of cancer and the availability of tailored therapies have exposed opportunities for improvements in diagnostic precision.

Clinicopathological significance of lipocalin 2 nuclear expression in invasive breast cancer.

Purpose: The epithelial-mesenchymal transition (EMT) plays a key role in breast cancer progression and metastasis. Lipocalin 2 (LCN2) is involved in the regulation of EMT. The aim of this study was to investigate the clinicopathological significance of LCN2 expression in breast cancer.

Utility of ankyrin 3 as a prognostic marker in androgen-receptor-positive breast cancer.

Purpose: Androgen receptor (AR) and AR signaling pathways are thought to play a role in breast cancer (BC) and are potentially related to treatment responses and outcomes. Ankyrin 3 (ANK3) is associated with AR stability in cancer cells. In the present study, we investigated the clinicopathological utility of ANK3 expression with emphasis on AR and its associated signalling pathway at transcriptomic and proteomic phases.

Clinicopathological and prognostic significance of Ras association and pleckstrin homology domains 1 (RAPH1) in breast cancer.

Background: Ras association and pleckstrin homology domains 1 (RAPH1) is involved in cytoskeleton regulation and re-epithelialisation in invasive carcinoma and, therefore, may play a key role in carcinogenesis and metastasis. We, herein, investigated the biological and clinical significance of RAPH1 in breast cancer using large annotated cohorts.

Methods: The clinicopathological and prognostic significance of RAPH1 was assessed at the genomic and transcriptomic levels using The Cancer Genome Atlas (TCGA) dataset (n = 1039) and the results were validated using the Molecular taxonomy of breast cancer international consortium (METABRIC) cohort (n = 1980).

Diagnostic challenges in papillary lesions of the breast.

Papillary lesions of the breast comprise a heterogeneous group of diseases ranging from benign and atypical lesions to malignant tumours including non-invasive and invasive entities. Although diagnosis of papillary lesions featuring typical histological features is straightforward, a proportion shows overlapping features, posing diagnostic challenges. In addition to being uncommon, the excellent behaviour of papillary tumours reduces the distinguishing value of individual histological features and increases the subjectivity of interpretation of various diagnostic features.

Evaluation of CDK12 Protein Expression as a Potential Novel Biomarker for DNA Damage Response-Targeted Therapies in Breast Cancer.

Disruption of Cyclin-Dependent Kinase 12 () is known to lead to defects in DNA repair and sensitivity to platinum salts and PARP1/2 inhibitors. However, has also been proposed as an oncogene in breast cancer. We therefore aimed to assess the frequency and distribution of CDK12 protein expression by IHC in independent cohorts of breast cancer and correlate this with outcome and genomic status.

Ki67 expression in invasive breast cancer: the use of tissue microarrays compared with whole tissue sections.

Background: Although the prognostic value of Ki67 in breast cancer is well documented, using optimal cut-points for patient stratification, reproducibility of the scoring and interpretation of the results remains a matter of debate particularly when using tissue microarrays (TMAs). This study aims to assess Ki67 expression assessed on TMAs and their matched whole tissue sections (WTS). Moreover, whether the cut-off used for WTS is reproducible on TMA in BC molecular classes and the association between Ki67 expression cut-off, assessed on TMAs and WTS, and clinicopathological parameters and patient outcome were tested.

Prognostic significance of tumour infiltrating B lymphocytes in breast ductal carcinoma in situ.

Aims: Tumour-infiltrating lymphocytes (TILs) are an important component of the immune response to cancer and have a prognostic value in breast cancer. Although several studies have investigated the role of T lymphocytes in breast cancer, the role of B lymphocytes (TIL-Bs) in ductal carcinoma in situ (DCIS) remains uncertain. This study aimed to assess the role of TIL-Bs in DCIS.

Further evidence to support bimodality of oestrogen receptor expression in breast cancer.

Aims: Although oestrogen receptor (ER)-negative breast cancers (BCs) do not respond to hormone therapy, the response of ER-positive BCs is reported to be variable, which may suggest a dose-dependent effect. The aim of this study was to assess the pattern of ER expression in BCs at the protein (immunohistochemistry) and transcriptome (microarray-based gene expression) levels.

Methods And Results: ER immunohistochemical (IHC) expression was assessed in a large series of BCs, including 3649 core biopsies and 1892 cases prepared as tissue microarrays (TMAs) stained with specific antibodies.

Clinicopathological and prognostic significance of mitogen-activated protein kinases (MAPK) in breast cancers.

Background: Mitogen-activated protein kinases (MAPKs) are signalling transduction molecules that have different functions and diverse behaviour in cancer. In breast cancer, MAPK is related to oestrogen receptor (ER) and HER2.

Methods: Protein expression of a large panel of MAPKs (JNK1/2, ERK, p38, C-JUN and ATF2 including phosphorylated forms) were assessed immunohistochemically in a large (n = 1400) and well-characterised breast cancer series prepared as tissue microarray.

Clinical and biological significance of RAD51 expression in breast cancer: a key DNA damage response protein.

Impaired DNA damage response (DDR) may play a fundamental role in the pathogenesis of breast cancer (BC). RAD51 is a key player in DNA double-strand break repair. In this study, we aimed to assess the biological and clinical significance of RAD51 expression with relevance to different molecular classes of BC and patients' outcome.

Impact of intratumoural heterogeneity on the assessment of Ki67 expression in breast cancer.

In breast cancer (BC), the prognostic value of Ki67 expression is well-documented. Intratumoural heterogeneity (ITH) of Ki67 expression is amongst the several technical issues behind the lag of its inclusion into BC prognostic work-up. The immunohistochemical (IHC) expression of anti-Ki67 antibody (MIB1 clone) was assessed in four full-face (FF) sections from different primary tumour blocks and their matched axillary nodal (LN) metastases in a series of 55 BC.