Assessment of associations between clinical and immune microenvironmental factors and tumor mutation burden in resected nonsmall cell lung cancer by applying machine learning to whole-slide images.

Background: It is unclear whether clinical factors and immune microenvironment (IME) factors are associated with tumor mutation burden (TMB) in patients with nonsmall cell lung cancer (NSCLC).

Materials And Methods: We assessed TMB in surgical tumor specimens by performing whole exome sequencing. IME profiles, including PD-L1 tumor proportion score (TPS), stromal CD8 tumor-infiltrating lymphocyte (TIL) density, and stromal Foxp3 TIL density, were quantified by digital pathology using a machine learning algorithm.

Comparison of Clinically Relevant Mutation Profiles Between Preoperative Biopsy and Corresponding Surgically Resected Specimens in Japanese Patients With Non-Small-cell Lung Cancer by Amplicon-based Massively Parallel Sequencing.

Background: Amplicon-based massively parallel sequencing (MPS) is an effective platform for identifying clinically actionable mutations across many genes in limited amounts of tissue. Most lung cancers are diagnosed and staged using small tissue samples obtained by transbronchial biopsy (TBB). To determine whether the mutations in TBB specimens detected by amplicon-based MPS reflect those present in the tumors, we compared the mutational profiles of preoperative TBB specimens and corresponding surgically resected specimens.

Prospective genetic profiling of squamous cell lung cancer and adenosquamous carcinoma in Japanese patients by multitarget assays.

Background: Despite considerable recent progress in the treatment of lung adenocarcinoma, there has been little progress in the development of efficacious molecular targeted therapies for squamous cell lung cancer. In addition to the recent comprehensive genome-wide characterization of squamous cell lung cancer, it is also important to genotype this form of cancer. We therefore conducted the Shizuoka Lung Cancer Mutation Study to analyze driver mutations in patients with thoracic malignancies.

Assessment of mutational profile of Japanese lung adenocarcinoma patients by multitarget assays: a prospective, single-institute study.

Background: Integration of mutational profiling to identify driver genetic alterations in a clinical setting is necessary to facilitate personalized lung cancer medicine. A tumor genotyping panel was developed and the Shizuoka Lung Cancer Mutation Study was initiated as a prospective tumor genotyping study. This study reports the frequency of driver genetic alterations in Japanese lung adenocarcinoma patients, and clinicopathologic correlations with each genotype.

Novel protein extraction approach using micro-sized chamber for evaluation of proteins eluted from formalin-fixed paraffin-embedded tissue sections.

We describe a novel antigen-retrieval method using a micro-sized chamber for mass spectrometry (MS) analysis to identify proteins that are preferentially eluted from formalin-fixed paraffin-embedded (FFPE) samples. This approach revealed that heat-induced antigen retrieval (HIAR) from an FFPE sample fixed on a glass slide not only improves protein identification, but also facilitates preferential elution of protein subsets corresponding to the properties of antigen-retrieval buffers. Our approach may contribute to an understanding of the mechanism of HIAR.

18F-FDG uptake on PET in primary mediastinal non-thymic neoplasm: a clinicopathological study.

Background: The usefulness of 2-[(18)F]-fluoro-2-deoxy-D-glucose ((18)F-FDG) positron emission tomography (PET) has been investigated in thymic epithelial tumors. However, little is known about PET imaging of (18)F-FDG in primary non-thymic mediastinal neoplasms. The aim of this study is to explore the clinicopathological significance of (18)F-FDG PET in primary mediastinal (non-thymic) neoplasms.

Biologic correlates of ¹⁸F-FDG uptake on PET in pulmonary pleomorphic carcinoma.

Background: Pulmonary pleomorphic carcinoma is a rare epithelial tumor, and little is also known about the information on the usefulness of 2-[¹⁸F]-fluoro-2-deoxy-d-glucose (¹⁸F-FDG) positron emission tomography (PET). Therefore, we conducted the study including the underlying biologic analysis of ¹⁸F-FDG uptake.

Methods: Fifteen patients with pulmonary pleomorphic carcinoma who underwent ¹⁸F-FDG PET before treatment were included in this study.

Biologic correlation of 2-[18F]-fluoro-2-deoxy-D-glucose uptake on positron emission tomography in thymic epithelial tumors.

Purpose: The usefulness of 2-[(18)F]-fluoro-2-deoxy-D-glucose ([(18)F]FDG) positron emission tomography (PET) can help predict the grade of malignancy and staging in thymic epithelial tumors. However, no satisfactory biologic explanation exists for this phenomenon. The aim of this study was to investigate the underlying biologic mechanisms of [(18)F]FDG uptake.

Optimal extent of lymph node dissection for T1 gastric cancer, with special reference to the distribution of micrometastasis, and accuracy of preoperative diagnosis for wall invasion.

Background/aims: Preoperative diagnosis for wall invasion and lymph node metastasis is sometimes difficult in T1 gastric cancer. Optimum dissection extent of lymph nodes for T1 gastric cancer was studied from the aspect of subclassification of wall invasion and lymph node metastasis including micrometastasis.

Methodology: 184 patients with cT1 or pT1 gastric cancer were studied.

Cartilaginous features in matrix-producing carcinoma of the breast: four cases report with histochemical and immunohistochemical analysis of matrix molecules.

Matrix-producing carcinoma of the breast is a well-established entity in the group of metaplastic carcinoma, which is histologically characterized by myxochondroid matrix formation and is extremely rare. We describe here four additional cases of matrix-producing carcinoma of the breast. All cases of matrix-producing carcinoma show nest-like, sheet-like, and cord-like growth of tumor cells with cellular atypia, in addition to scattered cancer cells within myxoid or myxohyalinous stroma.

Evaluation of lymphatic invasion in primary gastric cancer by a new monoclonal antibody, D2-40.

Lymphatic invasion is known as an independent predictor of lymph node metastasis in gastric cancer. However, the diagnosis of lymphatic invasion is sometimes difficult by hematoxylin-eosin (H&E) staining. Immunostaining using D2-40 was performed to study the distribution of lymphatic vessel and lymphatic invasion in a series of 78 primary gastric cancers.

A < 1.7 cM interval is responsible for Dmo1 obesity phenotypes in OLETF rats.

1. Dmo1 (Diabetes Mellitus OLETF type I) is a major quantitative trait locus for dyslipidaemia, obesity and diabetes phenotypes of male Otsuka Long Evans Tokushima Fatty (OLETF) rats. 2.

Difference in cytoplasmic localization pattern of neutral mucin among lobular endocervical glandular hyperplasia, adenoma malignum, and common adenocarcinoma of the uterine cervix.

To investigate whether the cytoplasmic localization pattern of neutral mucin differs between lobular endocervical glandular hyperplasia (LEGH) and cervical adenocarcinoma (CxAd), including minimal-deviation adenocarcinoma (MDA), or adenoma malignum, alcian blue (pH 2.5)/periodic acid-Schiff (AB-PAS) staining was performed to formalin-fixed paraffin-embedded tissue sections of 13 lesions of LEGH and 53 tumors of CxAd, including 6 tumors of MDA. The cytoplasmic localization of neutral mucin was classified as a "whole cytoplasmic pattern," in which neutral mucin filled the cytoplasm entirely, or as an "apical pattern," in which neutral mucin was localized in the subsurface area only.

Interobserver variation in the diagnosis of adenoma malignum (minimal deviation adenocarcinoma) of the uterine cervix.

To examine the interobserver agreement level of the histological diagnosis of adenoma malignum (ADM), 52 proliferative endocervical glandular lesions were evaluated independently by four observers (A to D), each of whom is in charge of gynecological pathology at a different hospital. The correlation of diagnosis by each observer with patient outcome was also examined for 19 of these lesions. When the diagnoses were categorized into benign lesions including hyperplasias, ADM, and common types of adenocarcinoma, consistent diagnoses among all observers were achieved for only 12 lesions (23%), with a slight level of interobserver agreement (kappa=0.