Analysis of recurrent molecular alterations in phyllodes tumour of breast: insights into prognosis and pathogenesis.

Phyllodes tumour (PT) of breast is a rare biphasic neoplasm. Recent next generation sequencing analyses had revealed novel genetic alterations in PT but lacked a further characterisation of their relationship to different PT features and outcome. Here, using targeted sequencing, we examined a panel of 90 recurrently altered or cancer related genes in 88 PT samples (including 49 benign, 25 borderline and 14 malignant PT).

SETD2 alterations and histone H3K36 trimethylation in phyllodes tumor of breast.

Purpose: SETD2 is one of the key epigenetic regulatory genes involved in histone modifications. Its alterations were potentially oncogenic and commonly found in cancers. Interestingly, SETD2 is one of the most frequent mutated genes found exclusively in phyllodes tumor of the breast (PT).

Co-expression of HLA-I loci improved prognostication in HER2+ breast cancers.

The underlying basis for cancer immune evasion is important for effective immunotherapy and prognosis in breast cancers. Human leucocyte antigens (HLA)-I comprising three classical antigens (HLA-A, -B and -C) is mandatory for anti-tumor immunity. Its loss occurred frequently in many cancers resulting in effective immune evasion.

Diagnostic upgrade of atypical ductal hyperplasia of the breast based on evaluation of histopathological features and calcification on core needle biopsy.

Aims: Atypical ductal hyperplasia (ADH) of breast is increasingly diagnosed in core needle biopsy (CNB). As higher-grade lesions were found in the excision in a substantial proportion of ADH on CNB, factors predicting risk of subsequent upgrade are clinically significant. This study aims to investigate relevant histopathological factors in CNB that could predict diagnostic upgrade at excision.

Expression of biomarkers in the AKT pathway correlates with malignancy and recurrence in phyllodes tumours of the breast.

Aims: Phyllodes tumours (PTs) of the breast are uncommon fibroepithelial neoplasms with the potential to recur and metastasise. Apart from histological grading, the expression of biological markers and its relationship with tumour behaviour have been topics of interest. The phosphatidylinositol 3-kinase (PI3K)-AKT pathway regulates diverse biological functions, and is one of the most frequently deregulated pathways in cancers.

Core needle biopsy as an alternative to whole section in IHC4 score assessment for breast cancer prognostication.

Aims: IHC4 score, based on expression of four routine markers (oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and proliferation marker, Ki67), is a recently developed, cost-effective prognostic tool in breast cancer. Possibly, the score may be useful also in advanced diseases where only core needle biopsy (CNB) is available and neoadjuvant therapy. However, its studies on CNB are scant.

The Clinical Value of PELP1 for Breast Cancer: A Comparison with Multiple Cancers and Analysis in Breast Cancer Subtypes.

Purpose: Proline, glutamic acid, and leucine-rich protein 1 (PELP1), a novel nuclear receptor (NR) co-regulator, is highly expressed in breast cancer. We investigated its expression in breast cancer subtypes, in comparison with other breast markers as well as cancers from different sites. Its prognostic relevance with different subtypes and other NR expression was also examined in breast cancers.

Amyloid Precursor Protein Is Associated with Aggressive Behavior in Nonluminal Breast Cancers.

Background: β-amyloid precursor protein (APP), a potential target for Alzheimer's disease treatment, has recently been shown to take part in carcinogenesis. Increased APP promotes migration, survival, and proliferation in breast cancer cell lines. We examined the clinical value of APP in breast cancers.

CD147 expression is associated with poor overall survival in chemotherapy treated triple-negative breast cancer.

Aims: In breast cancer models, the functional roles of CD147 in proliferation, invasion and treatment resistance have been widely reported. However, there are only a few studies examining the clinicopathological correlation and prognostic relevance of CD147 in breast cancer, especially in relation to breast cancer molecular subtypes.

Methods: In this study, we analysed CD147 expression in a large cohort of breast cancers, correlating with clinicopathological features and the expression of a comprehensive panel of biomarkers in triple-negative breast cancer (TNBC) and non-TNBC subsets.

Association of clinicopathological features and prognosis of TERT alterations in phyllodes tumor of breast.

Phyllodes tumor (PT) of the breast is a rare but clinically important fibroepithelial tumor with potential risks of recurrence and metastasis. Recent studies identified recurrent TERT promoter mutations in PTs. However, the clinical significance of this alteration has not been fully examined.

GATA-3 is superior to GCDFP-15 and mammaglobin to identify primary and metastatic breast cancer.

Purpose: Despite numerous studies on the utility of GATA-3 as breast cancer marker, its comparison with other breast markers, its concordance between primary and metastatic tumors and its expression in primary cancers from sites with frequent breast metastases remains unclear.

Methods: To address these questions, totally 993 invasive breast cancers (IBC), 254 paired nodal metastases, 23 distant metastases, and 208 lung carcinomas were included. GATA-3 expression was analyzed by immunohistochemistry and compared to other breast markers [gross cystic disease fluid protein 15 (GCDFP-15) and mammaglobin (MGB)].

Integrative single-cell and cell-free plasma RNA transcriptomics elucidates placental cellular dynamics.

The human placenta is a dynamic and heterogeneous organ critical in the establishment of the fetomaternal interface and the maintenance of gestational well-being. It is also the major source of cell-free fetal nucleic acids in the maternal circulation. Placental dysfunction contributes to significant complications, such as preeclampsia, a potentially lethal hypertensive disorder during pregnancy.

Distinct Tertiary Lymphoid Structure Associations and Their Prognostic Relevance in HER2 Positive and Negative Breast Cancers.

Background: The presence of tumor infiltrating lymphocytes (TIL) is associated with favorable prognosis. Recent evidence suggested that not only their density, but also the spatial organization as tertiary lymphoid structures (TLS), play a key role in determining patient survival.

Materials And Methods: In a cohort of 248 breast cancers, the clinicopathologic association and prognostic role of TLS was examined.

Expression and Clinical Significance of Herpes Virus Entry Mediator (HVEM) in Breast Cancer.

Background: Immune checkpoint blockades are currently actively investigated in invasive breast cancers. Given the complexity of immune regulation, multiple inhibitory molecules within the immune checkpoint framework would be involved in tumor immune escape. Evaluation of the components within the framework is a prerequisite for not only identification of additional treatment targets and optimization of immunotherapeutic strategies but also understanding the prognostic value of these molecules.

Atypical aspirates of the breast: a dilemma in current cytology practice.

Aims: The probabilistic approach is widely adopted for breast fine needle aspiration cytology. However, a definite cytological diagnosis is not always possible for C3 (atypia) cases, which poses a management dilemma as this represents a mixed category of benign and malignant cases. It would be beneficial to be able to predict malignancy based on specific cytological features in C3 aspirates.

Intratumoral Heterogeneity in Breast Cancer: A Comparison of Primary and Metastatic Breast Cancers.

Intratumoral heterogeneity presents challenges in the management of cancer. To gain deeper insight in intratumoral heterogeneity at different levels and tumor sites for common biomarkers in breast cancers, this report examines seven cases of invasive breast cancer with multiple axillary nodal metastases and/or recurrences for immunohistochemical expression of estrogen receptors, progesterone receptors, human epidermal growth receptor 2, and Ki67 on all tissue blocks in both primary and metastatic tumors. 2017;22:487-490.

PD-L1 expression and tumor infiltrating PD-1+ lymphocytes associated with outcome in HER2+ breast cancer patients.

Purpose: Clinical trials showing programmed death (PD)-1-PD-ligand 1 (L1) axis as a promising therapeutic target in melanoma and non-small cell lung cancers have made the pathway a focus of recent attention. However, the data regarding PD-L1/PD-1 in breast cancer are inconsistent. Given the heterogeneity of breast cancers, the clinical relevance of PD-L1 and PD-1 tumor infiltrating lymphocytes (TIL) may vary according to subtypes of breast cancer.

Hyaluronan synthase 2 is an adverse prognostic marker in androgen receptor-negative breast cancer.

Aims: The important role of hyaluronan synthase 2 (HAS2), an isozyme responsible for hyaluronan synthesis, in cancer has been increasingly recognised. However, only a few studies with inconsistent results have been reported in breast cancers. With a large cohort, we aim to determine the clinical significance of HAS2 in breast cancers.

Pathological criteria and practical issues in papillary lesions of the breast - a review.

Papillary lesions of the breast include a broad spectrum of lesions, ranging from benign papilloma, papilloma with atypical ductal hyperplasia (ADH) or ductal carcinoma in situ (DCIS) to papillary carcinoma. The accurate diagnosis of mammary papillary lesions is a challenge for pathologists, owing to the overlapping features among these lesions. In this review, some of the diagnostic criteria of papillary lesions are discussed, with special emphasis on some key morphological features, namely fibrovascular cores, epithelial proliferation in a solid pattern, intraductal papilloma complicated by ADH or DCIS, and invasion and its mimics.

FGFR1 is an adverse outcome indicator for luminal A breast cancers.

Fibroblast growth factor receptor 1 (FGFR1) has been suggested to be the candidate gene for 8p11-12 amplification in breast cancer and its therapeutic/ prognostic value is explored. Most previous studies focused on FGFR1 gene amplification, which may not necessarily lead to protein expression. Therefore, analysis of protein level may have more clinical relevance.

Doublecortin-like kinase 1 expression associates with breast cancer with neuroendocrine differentiation.

Doublecortin-like kinase 1 (DCLK1), a microtubule associated kinase, has recently been proposed to be a putative marker for stemness and adverse prognosis in gastrointestinal cancers. However, it is not clear whether the protein also plays similar roles in breast cancer. Here, the expression of DCLK1 was analyzed in a large cohort of invasive breast cancers (IBC) by immunohistochemistry.

Lymphocyte subsets contribute to the degree of lobulitis and ductitis in sclerosing lymphocytic lobulitis of the breast.

Aims: Sclerosing lymphocytic lobulitis (SLL) of the breast is characterised by lymphocytic lobulitis, ductitis, vasculitis and dense keloidal fibrosis with epithelioid fibroblasts. However, the subsets of the infiltrating lymphocytes and their contribution to disease progression have not been fully explored.

Methods: CD20, CD3, CD4, CD8 and regulatory T (Treg) lymphocytes were evaluated in the epithelial and vascular areas in SLL.

Associations of epithelial c-kit expression in phyllodes tumours of the breast.

Background: Mammary phyllodes tumours (PT) are rare biphasic neoplasms but have important clinical significance. Both epithelial and stromal components participate in PT development. Despite a number of studies on stromal c-kit in PT, little is known about the role of its epithelial expression.

Anterior Gradient 2 is a Poor Outcome Indicator in Luminal Breast Cancer.

Background: Recent data have shown anterior gradient 2 (AGR2) to be a novel oncogene overexpressed in luminal breast cancers. However, many studies only focused on its relationship with treatment resistance, and the clinical relevance of AGR2 has not been widely evaluated.

Methods: AGR2 expression in a cohort of breast cancer was correlated with the clinicopathologic features, biomarker expression, and patient survival.