Granzyme B Expression in the Tumor Microenvironment as a Prognostic Biomarker for Patients with Triple-Negative Breast Cancer.

Tumor-infiltrating lymphocytes in the tumor microenvironment are important in the treatment of triple-negative breast cancer (TNBC). Cytotoxic T cells produce cytokines and cytotoxic factors, such as perforin and granzyme, which induce apoptosis by damaging target cells. To identify biomarkers of these cells, we investigated granzyme B (GZMB) in the tumor microenvironment as a biomarker of treatment response and prognosis in 230 patients with primary TNBC who underwent surgery without preoperative chemotherapy between January 2004 and December 2014.

An evaluation of lymphovascular invasion in relation to biology and prognosis according to subtypes in invasive breast cancer.

Lymphovascular invasion (LVI) is associated with a poor outcome in breast cancer. The purpose of the present study was to evaluate the clinical significance of LVI in primary breast cancer and to investigate disease-free survival as a prognostic marker according to the breast cancer subtypes. This study examined 4,652 consecutive cases of invasive breast cancer excluding the patients with non-invasive cancer, stage IV and those who underwent neo-adjuvant therapy from February 2002 to February 2021.

Triple Negative Breast Cancer: An Analysis of the Subtypes and the Effects of Menopausal Status on Invasive Breast Cancer.

Background: Triple negative breast cancer (TNBC) is a subtype of breast cancer which lacks hormone receptor (HR) expression and HER2 gene amplification and is the most aggressive subtype, with a heterogeneous genetic profile. The aim of this retrospective study was to evaluate the clinical significance of menopausal status in breast cancer cases with TNBC.

Methods: Primary breast cancer patients who underwent curative surgery were enrolled in this retrospective study.

INSM1 immunostaining in solid papillary carcinoma of the breast.

Solid papillary carcinoma (SPC) is a histological subtype of breast carcinomas. At least 50% of SPC show neuroendocrine differentiation. Insulinoma-associated protein 1 (INSM1) is a transcription factor now employed as a useful neuroendocrine marker.

Incidence, predictive factors and severity of methotrexate-related liver injury in rheumatoid arthritis: a longitudinal cohort study.

Objectives: The aims were to determine the incidence rate, predictive factors and severity of liver injury that develops during MTX treatment for RA and to evaluate the role of pretreatment hepatic fat deposition.

Methods: We used an ongoing real-life registry containing RA patients who had started MTX between August 2007 and April 2018 at participating institutions. The liver-to-spleen attenuation ratio on CT scans at enrolment was used to evaluate pretreatment fat deposition quantitatively.

Single administration of avelumab induced a complete response in thyroid transcription factor 1-positive combined Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is an aggressive neoplasm and patients with metastasis have poor survival outcomes. Recently, avelumab, an anti-programmed death ligand 1 (PD-L1) immune checkpoint inhibitor, was approved for first-line treatment in patients with metastatic MCC. While the administration interval of avelumab is every 2 weeks, the durable effect of a single administration of avelumab is unknown.

Microsatellite instability in Japanese female patients with triple-negative breast cancer.

Background: It is important to identify biomarkers for triple-negative breast cancers (TNBCs). Recently, pembrolizumab, an immune checkpoint inhibitor (ICI) for programmed cell death 1 (PD-1), was approved as a treatment strategy for unresectable or metastatic tumor with high-frequency microsatellite instability (MSI-H) or mismatch repair deficiency, such as malignant melanoma, non-small cell lung cancer, renal cell cancer and urothelial cancer. In addition, results from clinical trials suggested that ICI was a promising treatment for TNBCs with accumulated mutations.

T-bet lymphocytes infiltration as an independent better prognostic indicator for triple-negative breast cancer.

Purpose: T-box transcription factor 21 (T-bet), which is the master regulator of effector T-cell activation, is derived by stimulation of T-cell receptors. In this study, we focused on T-bet and examined the function of activated T cells.

Methods: This study included 242 patients with primary triple-negative breast cancer (TNBC) who underwent resection without neoadjuvant chemotherapy between January 2004 and December 2014.

Ki-67 index value and progesterone receptor status can predict prognosis and suitable treatment in node-negative breast cancer patients with estrogen receptor-positive and HER2-negative tumors.

Gene profiling has identified at least 4 breast cancer subtypes, including Luminal A, Luminal B, HER2-enriched and basal-like, and immunohistochemistry is used as a guide to determine these subtypes. In the present study, patients with ER-positive, HER2-negative and negative nodes were classified into 4 groups according to the PgR and the Ki-67 status and were retrospectively examined. The analysis was based on the clinicopathological findings, and includes the recurrence score (RS) and disease-free survival (DFS) rates.

Non-alcoholic steatohepatitis-like pattern in liver biopsy of rheumatoid arthritis patients with persistent transaminitis during low-dose methotrexate treatment.

Objective: The mechanism of liver injury with low-dose methotrexate (MTX) is incompletely understood. This study was designed to evaluate the association between non-alcoholic fatty liver disease (NAFLD) and liver injury during MTX treatment for rheumatoid arthritis (RA).

Methods: Between October 2014 and May 2015, we enrolled all MTX users for RA and monitored participant serum hepatic transaminase levels for 1 year.

Usefulness of virtual touch quantification for staging liver fibrosis in patients with hepatitis C, and factors affecting liver stiffness measurement failure compared with liver biopsy.

Aim: The assessment of liver fibrosis in patients with hepatitis C is important to predict carcinogenesis. In this study, we evaluated the usefulness of virtual touch quantification (VTQ) for staging liver fibrosis, and investigated factors causing discrepancies between the estimated fibrosis stage using VTQ and the pathological fibrosis stage.

Methods: Patients with hepatitis C (n = 302) were assessed using VTQ and underwent pathological liver investigation within 1 week before and after VTQ.

Role of HER2-Related Biomarkers (HER2, p95HER2, HER3, PTEN, and PIK3CA) in the Efficacy of Lapatinib plus Capecitabine in HER2-Positive Advanced Breast Cancer Refractory to Trastuzumab.

Objective: The aim of this study was to investigate the correlation between human epidermal growth factor receptor 2 (HER2)-related biomarkers and the treatment outcomes using lapatinib plus capecitabine (LC) and to evaluate the influence of the estrogen receptor (ER) status in trastuzumab-refractory HER2-positive advanced breast cancer.

Method: Eighty patients were enrolled in this study. Total HER2, p95HER2, and total HER3 expression were quantified using the VeraTag assays.

Evaluation of ALDH1 expression in ipsilateral breast cancer recurrence.

Aldehyde dehydrogenase 1 (ALDH1) is a cancer stem cell (CSC) marker that is easily evaluable. The expression and clinical significance of ALDH1 in ipsilateral breast tumor recurrence (IBTR) has yet to be investigated. In the present study, the expression profile of ALDH1 and its correlation with prognosis in IBTR tissues was examined.

The combination of PD-L1 expression and decreased tumor-infiltrating lymphocytes is associated with a poor prognosis in triple-negative breast cancer.

This study included patients with primary triple-negative breast cancer (TNBC) who underwent resection without neoadjuvant chemotherapy between January 2004 and December 2014. Among the 248 TNBCs studied, programmed cell death ligand-1 (PD-L1) expression was detected in 103 (41.5%) tumors, and high levels of tumor-infiltrating lymphocytes (TILs) were present in 118 (47.

BRCAness as a Biomarker for Predicting Prognosis and Response to Anthracycline-Based Adjuvant Chemotherapy for Patients with Triple-Negative Breast Cancer.

Background: Triple-negative breast cancer (TNBC) is a heterogeneous tumor that encompasses many different subclasses of the disease. In this study, we assessed BRCAness, defined as the shared characteristics between sporadic and BRCA1-mutated tumors, in a large cohort of TNBC cases.

Methods: The BRCAness of 262 patients with primary TNBCs resected between January 2004 and December 2014 was determined through the isolation of DNA from tumor tissue.

[Diffuse large B-cell lymphoma developed newly after 9-year remission of a follicular lymphoma].

Follicular lymphoma (FL) occasionally transforms into diffuse large B-cell lymphoma (DLBCL). This is generally associated with a poor prognosis, necessitating more potent chemotherapy as salvage treatment. However, de novo DLBCL, but not DLBCL transformed from FL, can be treated as primary DLBCL.

A Comparison of the Hot Spot and the Average Cancer Cell Counting Methods and the Optimal Cutoff Point of the Ki-67 Index for Luminal Type Breast Cancer.

Objective: In this case-control study, we investigated the most suitable cell counting area and the optimal cutoff point of the Ki-67 index.

Methods: Thirty recurrent cases were selected among hormone receptor (HR)-positive/HER2-negative breast cancer patients. As controls, 90 nonrecurrent cases were randomly selected by allotting 3 controls to each recurrent case based on the following criteria: age, nodal status, tumor size, and adjuvant endocrine therapy alone.

The importance of tissue handling of surgically removed breast cancer for an accurate assessment of the Ki-67 index.

Aim: Insufficient attention for the Ki-67 immunohistochemistry has been given to the importance of tissue handling for surgical breast cancer specimens. We sought to investigate the effect of fixation status on the Ki-67.

Methods: We examined the effect of fixative, time to and duration of fixation using surgical specimens, and finally, compared the paired Ki-67 index in the tumour between core needle and surgical specimen.

Evaluation of an Optimal Cut-Off Point for the Ki-67 Index as a Prognostic Factor in Primary Breast Cancer: A Retrospective Study.

The Ki-67 index is an important biomarker for indicating the proliferation of cancer cells and is considered to be an effective prognostic factor for breast cancer. However, a standard cut-off point for the Ki-67 index has not yet been established. Therefore, the aim of this retrospective study was to determine an optimal cut-off point in order to establish it as a more accurate prognostic factor.

Survival time according to the year of recurrence and subtype in recurrent breast cancer.

Background: Survival for patients with recurrent breast cancer has improved over time due to the introduction of modern systemic therapy. The aim of this study was to determine the impact of subtype and the year of recurrence on the survival times of recurrent breast cancer.

Methods: Between 1979 and 2013, 813 patients who underwent initial treatment for primary breast cancer experienced recurrence.

Efficacy of intraoperative entire-circumferential frozen section analysis of lumpectomy margins during breast-conserving surgery for breast cancer.

Background: Intraoperative frozen section analysis of the surgical margins during breast-conserving surgery (BCS) for breast cancer can reliably achieve clear surgical margins and prevent re-operations. The aim of this study was to assess intraoperative entire-circumferential frozen section analysis (IEFSA) of the lumpectomy margins during BCS.

Methods: A total of 1029 patients who underwent BCS with IEFSA between June 2007 and July 2013 were available for assessment.

Androgen receptor and enzymes in lymph node metastasis and cancer reoccurrence in triple-negative breast cancer.

Background: Triple-negative breast cancer (TNBC) is characterized by the absence of estrogen receptor, progesterone receptor and HER2. TNBCs are a diverse subgroup, but one promising marker and therapeutic target of this breast cancer is the androgen receptor (AR). Previously we demonstrated that AR and cognate intracrine pathways are associated with decreased proliferation in invasive ductal carcinoma with their decrease also detected between organ-confined and invasive diseases.

Prognostic significance of Ki-67 index value at the primary breast tumor in recurrent breast cancer.

The Ki-67 index value is a prognostic factor in primary breast cancer and is a proliferation marker that also distinguishes between luminal type A and type B breast cancer. Moreover, a change in Ki-67 index values due to treatment and recurrence is considered to be important in treating breast cancer. In this study, we investigated whether the baseline Ki-67 value in the primary tumor is useful as a prognostic factor following disease recurrence.