Performance of HER2 DAKO HercepTest and Ventana 4B5 immunohistochemical assays on detecting HER2 gene-amplification in uterine serous carcinomas.

We compared the performance of two commonly-used HER2 immunohistochemistry (IHC) assays in uterine serous carcinomas (USC), correlating with HER2 gene amplification by fluorescence in-situ hybridization (FISH). Sixty-five USCs were stained by both HercepTest™ and PATHWAY 4B5 assays. FISH was performed by HER2 IQFISH pharmDx.

Interobserver and Interantibody Reproducibility of HER2 Immunohistochemical Scoring in an Enriched HER2-Low-Expressing Breast Cancer Cohort.

Objectives: We assessed the interobserver and interantibody reproducibility of HER2 immunohistochemical scoring in an enriched HER2-low-expressing breast cancer cohort.

Methods: A total of 114 breast cancer specimens were stained by HercepTest (Agilent Dako) and PATHWAY anti-HER2 (4B5) (Ventana) antibody assays and scored by 6 breast pathologists independently using current HER2 guidelines. Level of agreement was evaluated by Cohen κ analysis.

The Rochester Modified Magee Algorithm (RoMMa): An Outcomes Based Strategy for Clinical Risk-Assessment and Risk-Stratification in ER Positive, HER2 Negative Breast Cancer Patients Being Considered for Oncotype DX Testing.

Introduction: Multigene genomic profiling has become the standard of care in the clinical risk-assessment and risk-stratification of ER, HER2 breast cancer (BC) patients, with Oncotype DX (ODX) emerging as the genomic profile test with the most support from the international community. The current state of the health care economy demands that cost-efficiency and access to testing must be considered when evaluating the clinical utility of multigene profile tests such as ODX. Several studies have suggested that certain lower risk patients can be identified more cost-efficiently than simply reflexing all ER, HER2 BC patients to ODX testing.

HER2-low breast cancers: Current insights and future directions.

In light of the significant clinical benefits of novel HER2-targeting antibody-drug conjugates in advanced HER2-low expressing breast cancers in recent phases I and III clinical trials, particularly trastuzumab-deruxtecan (T-Dxd), the new "HER2-low" category in breast cancers (breast cancer with a HER2 IHC score of 1+, or 2+ without gene amplification) has gained increasing attention. In the past year, "HER2-low" breast cancers have been under active investigation by both oncologists and pathologists. In this current review, we update the recent cutting-edge research on HER2-low breast cancers, with a focus on the biology of HER2-low breast cancers, the issues on the identification of HER2-low breast cancers by immunohistochemistry in current practice of pathology, and the future directions in this emerging category in breast cancers.

Significance of HER2 in Microinvasive Breast Carcinoma.

Objectives: We compared the clinicopathologic features, clinical management, and outcomes of human epidermal growth factor receptor 2 (HER2)-expressing and nonexpressing microinvasive breast carcinomas (MiBC) to explore the significance of HER2 in MiBC.

Methods: Clinicopathologic and follow-up information of cases with final diagnosis of MiBC with known HER2 status between 2007 and 2019 were analyzed.

Results: Nineteen (41.

Frequency, Clinicopathologic Characteristics, and Follow-up of HER2-Positive Nonpleomorphic Invasive Lobular Carcinoma of the Breast.

Objectives: To investigate human epidermal growth factor receptor 2 (HER2)-positive nonpleomorphic invasive lobular carcinoma (ILC), which has rarely been addressed.

Methods: Clinicopathologic characteristics and follow-up of HER2-positive nonpleomorphic ILCs were collected and compared to those of HER2-negative counterparts.

Results: Twenty-one cases of HER2-positive nonpleomorphic ILCs were identified, 6.

Optical segmentation of unprocessed breast tissue for margin assessment.

Visual and tactual examination of unprocessed breast specimens is the standard for intraoperative surgical margin assessment in the United States. However, this procedure does not provide surgeons or pathologists with microscopic views of the tissue, which makes it difficult to accurately assess margin status or the extent of the disease, especially in non-palpable cases. We use a combination of spectral and polarization macroscopic imaging to optically segment the adipose and collagen tissues thus highlighting regions suspected of containing epithelium in order to facilitate optical microscopy techniques.

Design and validation of two optical beacons for guidewire localization in breast-conserving surgery.

Stereotactically placed guidewires are used for indicating the location of a nonpalpable carcinoma in breast-conserving surgery. Pathologists use the end of the embedded guidewire to guide sectioning during intraoperative margin assessment, but they do not currently have a tool to indicate the location of the guidewire end for informed sectioning. We present analysis and experimental testing of two optical methods for localizing the end of an embedded fiber-optic guidewire: the first uses irradiance emitted from the fiber to indicate the location of the guidewire end, while the second system uses the fiber optic to create a photoacoustic pulse for localization.

The ubiquitin E3 ligase WWP1 decreases CXCL12-mediated MDA231 breast cancer cell migration and bone metastasis.

Advanced breast cancers preferentially metastasize to bone where cells in the bone microenvironment produce factors that enhance breast cancer cell homing and growth. Expression of the ubiquitin E3 ligase WWP1 is increased in some breast cancers, but its role in bone metastasis has not been investigated. Here, we studied the effects of WWP1 and itch, its closest family member, on breast cancer bone metastasis.

Giant pancreatic tumor with clinical characteristics of insulinoma but without common pathologic features.

Objective: To report a case of a large pancreatic tumor that had clinical characteristics of an insulinoma without classic pathologic features.

Methods: We describe a 58-year-old woman who presented with a 3-month history of symptomatic hypoglycemic episodes, which were characterized by confusion. The laboratory, imaging, and pathologic findings are summarized, the current literature on giant insulinomas is reviewed, and the distinction between clinical and pathologic diagnosis of neuroendocrine tumors is discussed.

Heat shock protein 27 differentiates tolerogenic macrophages that may support human breast cancer progression.

Tumor cells release several factors that can help the progression of the tumor by directly supporting tumor growth and/or suppressing host antitumor immunity. Here, we report that human primary breast tumor cells not only express elevated levels of heat shock protein 27 (Hsp27) at the intracellular level but also release extremely high levels of Hsp27 compared with the same patients' serum Hsp27 levels, predicting an acutely increased concentration of soluble Hsp27 in the human breast tumor microenvironment (HBTM). We demonstrate that Hsp27 levels in the HBTM can be extremely elevated as evidenced by high soluble Hsp27 levels in patients' tumor interstitial fluid.

Comparative effectiveness of ductal carcinoma in situ management and the roles of margins and surgeons.

Background: The high incidence of ductal carcinoma in situ (DCIS) and variations in its treatment motivate inquiry into the comparative effectiveness of treatment options. Few such comparative effectiveness studies of DCIS, however, have been performed with detailed information on clinical and treatment attributes.

Methods: We collected detailed clinical, nonclinical, pathological, treatment, and long-term outcomes data from multiple medical records of 994 women who were diagnosed with DCIS from 1985 through 2000 in Monroe County (New York) and the Henry Ford Health System (Detroit, MI).

A lower Allred score for progesterone receptor is strongly associated with a higher recurrence score of 21-gene assay in breast cancer.

Among the 77 infiltrating breast carcinomas, we found that progesterone receptor (PR) expression was inversely associated with recurrence score (RS, p < .0001). RS is also significantly associated with tubule formation, mitosis, and luminal B subtype.

Confocal microscopy of unfixed breast needle core biopsies: a comparison to fixed and stained sections.

Background: Needle core biopsy, often in conjunction with ultrasonic or stereotactic guided techniques, is frequently used to diagnose breast carcinoma in women. Confocal scanning laser microscopy (CSLM) is a technology that provides real-time digital images of tissues with cellular resolution. This paper reports the progress in developing techniques to rapidly screen needle core breast biopsy and surgical specimens at the point of care.

Metastatic versus primary oncocytic papillary adenocarcinoma of the endometrium: a report of a case and review of the literature.

We report a case of an oncocytic papillary adenocarcinoma of the endometrium in an 89-year-old female with vaginal bleeding. Imaging studies revealed lesions in the uterus, kidneys, pancreas, gluteus, and an enlarged portacaval lymph node. Diagnostic workup included an endometrial biopsy which showed malignant, oncocytic cells in a predominantly papillary pattern.

The pen and the scalpel: effect of diffusion of information on nonclinical variations in surgical treatment.

Background: As information is disseminated about best practices, variations in patterns of care should diminish over time.

Objective: To test the hypotheses that differences in rates of a surgical procedure are associated with type of insurance in an era of evolving practice guidelines and that insurance and site differences diminish with time as consensus guidelines disseminate among the medical community.

Methods: We use lymph node dissection among women with ductal carcinoma in situ (DCIS) as an example of a procedure with uncertain benefit.

C35 (C17orf37) is a novel tumor biomarker abundantly expressed in breast cancer.

Identification of shared tumor-specific targets is useful in developing broadly applicable therapies. In a study designed to identify genes up-regulated in breast cancer, a cDNA clone corresponding to a novel gene C35 (C17orf37) was selected by representational difference analysis of tumor and normal human mammary cell lines. Abundant expression of C35 transcript in tumors was confirmed by Northern blot and real-time PCR.

Expression patterns of ER-alpha, PR, HER-2/neu, and EGFR in different cell origin subtypes of high grade and non-high grade ductal carcinoma in situ.

We have previously reported that high grade and non-high grade ductal carcinoma in situ (DCIS) of the breast can be subdivided into 3 cell origin subtypes (luminal, basal/stem, and null), and that high grade DCIS is more frequently associated with basal/stem cell subtypes compared to non-high grade DCIS. Here we refine the relationships between these 3 subtypes and the expression patterns of estrogen receptor-alpha (ER-alpha), progesterone receptor (PR), HER-2/neu, and epidermal growth factor receptor (ERFR) in 53 cases of non-high grade and 46 cases of high nuclear grade DCIS. Using a panel of antibodies to ER-alpha, PR, HER-2/neu, and EGFR, along with cytokeratin (CK) markers (CK5/6, CK8, CK14, CK17, and CK18), we found that all 3 cell origin subtypes can express ER-alpha and PR, and their expression is higher in non-high grade DCIS than in high grade DCIS; the expression of HER-2/neu is associated with luminal subtype only in non-high grade DCIS, but can be seen in all 3 subtypes in high grade DCIS; the expression of EGFR is low and is present only in luminal cell subtypes in both high and non-high grade DCIS.

Relationship between nuclear grade of ductal carcinoma in situ and cell origin markers.

Ductal carcinoma in situ (DCIS) is a group of heterogeneous lesions genetically, morphologically, and biologically. Recently, breast epithelium in the terminal ductal lobular unit has been sub-classified based on the expression of several cytokeratin markers as stem cells (CK5/6 +), luminal cells (CK8, CK18 +), and basal cells (CK14, CK17 +). In this study we describe the relationship between DCIS of different nuclear grades (non-high grade and high grade) and these cell origin markers.