Interobserver Variation in the Assessment of Immunohistochemistry Expression Levels in HER2-Negative Breast Cancer: Can We Improve the Identification of Low Levels of HER2 Expression by Adjusting the Criteria? An International Interobserver Study.

The classification of human epidermal growth factor receptor 2 (HER2) expression is optimized to detect HER2-amplified breast cancer (BC). However, novel HER2-targeting agents are also effective for BCs with low levels of HER2. This raises the question whether the current guidelines for HER2 testing are sufficiently reproducible to identify HER2-low BC.

Stromal Changes are Associated with High P4HA2 Expression in Ductal Carcinoma in Situ of the Breast.

Ductal carcinoma in situ (DCIS) of the breast is able to induce stromal changes, which likely reflect the crosstalk between DCIS and its microenvironment. These changes harbor prognostic information, although the interobserver variability of scoring stromal changes is moderate. A more robust evaluation of the DCIS-associated stroma is therefore needed.

Comparison of the tumor immune microenvironment of primary hormone receptor-negative HER2-positive and triple negative breast cancer.

The vast majority of studies investigating immune checkpoint inhibition (ICI) in patients with breast cancer have focused on triple-negative breast cancer (TNBC). In this study, we compared the tumor immune microenvironment (TIME) between TNBC and hormone receptor-negative HER2-positive breast cancer based on a selection of immune markers at the protein level in an institutional retrospective series. Additionally, we performed a similar comparison using publicly available transcriptomics data.

Interobserver variability in the assessment of stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative invasive breast carcinoma influences the association with pathological complete response: the IVITA study.

High stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative breast cancer (TNBC) are associated with pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). Histopathological assessment of sTILs in TNBC biopsies is characterized by substantial interobserver variability, but it is unknown whether this affects its association with pCR. Here, we aimed to investigate the degree of interobserver variability in an international study, and its impact on the relationship between sTILs and pCR.

A single-cell map of intratumoral changes during anti-PD1 treatment of patients with breast cancer.

Immune-checkpoint blockade (ICB) combined with neoadjuvant chemotherapy improves pathological complete response in breast cancer. To understand why only a subset of tumors respond to ICB, patients with hormone receptor-positive or triple-negative breast cancer were treated with anti-PD1 before surgery. Paired pre- versus on-treatment biopsies from treatment-naive patients receiving anti-PD1 (n = 29) or patients receiving neoadjuvant chemotherapy before anti-PD1 (n = 11) were subjected to single-cell transcriptome, T cell receptor and proteome profiling.

Interobserver variability in upfront dichotomous histopathological assessment of ductal carcinoma in situ of the breast: the DCISion study.

Histopathological assessment of ductal carcinoma in situ, a nonobligate precursor of invasive breast cancer, is characterized by considerable interobserver variability. Previously, post hoc dichotomization of multicategorical variables was used to determine the "ideal" cutoffs for dichotomous assessment. The present international multicenter study evaluated interobserver variability among 39 pathologists who performed upfront dichotomous evaluation of 149 consecutive ductal carcinomas in situ.

Stromal characteristics are adequate prognosticators for recurrence risk in ductal carcinoma in situ of the breast.

Background: Ductal carcinoma in situ (DCIS) of the breast constitutes a heterogeneous group of non-obligate precursors for invasive breast cancer. To date, adequate risk stratification is lacking, which is presumed to result in overtreatment. We previously identified myxoid stromal architecture as a potential prognosticator for loco-regional recurrence.

Dichotomous histopathological assessment of ductal carcinoma in situ of the breast results in substantial interobserver concordance.

Aims: Robust prognostic markers for ductal carcinoma in situ (DCIS) of the breast require high reproducibility and thus low interobserver variability. The aim of this study was to compare interobserver variability among 13 pathologists, in order to enable the identification of robust histopathological characteristics.

Methods And Results: One representative haematoxylin and eosin-stained slide was selected for 153 DCIS cases.

Accurate detection and quantification of epigenetic and genetic second hits in BRCA1 and BRCA2-associated hereditary breast and ovarian cancer reveals multiple co-acting second hits.

Background: This study characterizes the second hit spectrum in BRCA1 and BRCA2-associated breast and ovarian cancers at both gene loci to investigate if second hit mechanisms are mutually exclusive or able to coincide within the same tumor.

Methods: Loss of heterozygosity, somatic point mutations and copy number alterations along with promoter methylation were studied in 56 breast and 15 ovarian cancers from BRCA1 and BRCA2 germline mutation carriers. A mathematical methodology was introduced to quantify the tumor cell population carrying a second hit.

A plea for appraisal and appreciation of immunohistochemistry in the assessment of prognostic and predictive markers in invasive breast cancer.

This viewpoint is a personal reflection on the values and merits of immunohistochemistry in current breast cancer diagnosis. Immunohistochemistry is a validated mainstay in molecular subtyping of invasive breast cancer. Immunohistochemical assessment of hormone receptor status and HER2 expression is used to determine the clinico-pathological surrogate of breast cancer intrinsic subtypes, which guide neoadjuvant and adjuvant therapy.

Comparison of HER2 amplification status among breast cancer subgroups offers new insights in pathways of breast cancer progression.

Although the prognostic and predictive significance of human epidermal growth factor receptor 2 (HER2) in invasive breast cancer is well established, its role in ductal carcinoma in situ (DCIS) remains unclear. Reports on combined evaluation of both HER2 protein expression and HER2 amplification status in pure DCIS and DCIS adjacent to invasive ductal carcinoma (i.e.

Differential regulation of extracellular matrix protein expression in carcinoma-associated fibroblasts by TGF-β1 regulates cancer cell spreading but not adhesion.

Cancer progression is characterized by a complex reciprocity between neoplastic epithelium and adjacent stromal cells. In ductal carcinoma in situ (DCIS) of the breast, both reduced stromal decorin expression and myxoid stroma are correlated with increased recurrence risk. In this study, we aimed to investigate paracrine regulation of expression of decorin and related extracellular matrix (ECM) proteins in cancer-associated fibroblasts (CAFs).

Comparative analysis of cervical cytology and human papillomavirus genotyping by three different methods in a routine diagnostic setting.

Application of Bethesda guidelines on cervical cytology involves human papillomavirus (HPV) determinations on all ASC-US and ASC-H results. We compared HPV DNA results in view of the eventual development of a cervical intraepithelial neoplasia lesion determined either on cytology or histology. A total of 214 liquid-based cytology samples were analysed.

Cancer-associated adipose tissue promotes breast cancer progression by paracrine oncostatin M and Jak/STAT3 signaling.

Increasing evidence supports the critical roles played by adipose tissue in breast cancer progression. Yet, the mediators and mechanisms are poorly understood. Here, we show that breast cancer-associated adipose tissue from freshly isolated tumors promotes F-actin remodeling, cellular scattering, invasiveness, and spheroid reorganization of cultured breast cancer cells.

Histopathological characterization of ductal carcinoma in situ (DCIS) of the breast according to HER2 amplification status and molecular subtype.

This study aimed to characterize ductal carcinoma in situ (DCIS) according to human epidermal growth factor receptor 2 (HER2) amplification status and molecular subtype. In addition, we performed a detailed HER2 and CEP17 copy number analysis and we assessed the impact of recent changes in the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines on HER2 immunohistochemical (IHC) scores in DCIS. Nuclear grade, extensive comedonecrosis, stromal architecture, stromal inflammation, and progesterone receptor (PR) expression were significantly associated with HER2 amplification status.

Lymphoplasmacytic lymphoma exposed by haemoptysis and acquired von Willebrand syndrome.

We report on a 36-year-old man who presented to the emergency department with haemoptysis. Computed tomography (CT) of the thorax showed a pulmonary mass paramediastinal in the right upper lobe, with the density of a haematoma. Laboratory data demonstrated an absolute lymphocytosis of 5.

A nanobody targeting the F-actin capping protein CapG restrains breast cancer metastasis.

Introduction: Aberrant turnover of the actin cytoskeleton is intimately associated with cancer cell migration and invasion. Frequently however, evidence is circumstantial, and a reliable assessment of the therapeutic significance of a gene product is offset by lack of inhibitors that target biologic properties of a protein, as most conventional drugs do, instead of the corresponding gene. Proteomic studies have demonstrated overexpression of CapG, a constituent of the actin cytoskeleton, in breast cancer.

Distinguishing score 0 from score 1+ in HER2 immunohistochemistry-negative breast cancer: clinical and pathobiological relevance.

Objectives: To investigate the clinical and pathobiological significance of distinguishing score 0 and score 1+ within the group of immunohistochemistry (IHC)-negative invasive breast cancers.

Methods: We studied HER2 status using both IHC and fluorescence in situ hybridization (FISH) in 150 consecutive breast tumors submitted to our laboratory after a negative IHC result in local testing centers.

Results: We were able to discern a group of score 0 tumors that had a lower HER2 copy number than the group consisting of score 1+ tumors.

Stromal architecture and periductal decorin are potential prognostic markers for ipsilateral locoregional recurrence in ductal carcinoma in situ of the breast.

Aims: The incidence of ductal carcinoma in situ (DCIS) has increased since the introduction of screening mammography. Recurrence prediction is still not accurate, and could be improved by identifying additional prognostic markers. Periductal stroma actively participates in early breast cancer progression.

Radiation-induced myosin IIA expression stimulates collagen type I matrix reorganization.

Background And Purpose: Extracellular matrix (ECM) reorganization critically contributes to breast cancer (BC) progression and radiotherapy response. We investigated the molecular background and functional consequences of collagen type I (col-I) reorganization by irradiated breast cancer cells (BCC).

Materials And Methods: Radiation-induced (RI) col-I reorganization was evaluated for MCF-7/6, MCF-7/AZ, T47D and SK-BR-3 BCC.