Dynamic change of cancer genome profiling in metachronous bilateral breast cancer with pathogenic variant.

A 61-year-old woman with pathogenic variant had been treated for 20 years and showed dynamic changes in the genomic profile of her metachronous bilateral breast cancer and metastases. She underwent right breast conservation surgery at age 42-Genome 1, lung metastasis and left axillary lymph node metastasis at age 51, partial excision under local anesthesia for left breast cancer at age 53-Genome 2, left axillary lymph node dissection was added 6 month later-Genome 3. Then, olaparib was administered, and subsequently, left mastectomy was performed for the recurrence of left breast cancer at age 59-Genome 4.

The efficacy of bile liquid biopsy in the diagnosis and treatment of biliary tract cancer.

Background: Diagnosing biliary tract cancer is difficult because endoscopic retrograde cholangiopancreatography (ERCP) is performed fluoroscopically, and the sensitivity of bile cytology is low. Liquid biopsy of bile using targeted sequencing is expected to improve diagnosis and treatment, but few studies have been conducted. In this study, we examined whether liquid biopsy of bile improves the diagnostic sensitivity of biliary strictures.

Liquid biopsy of wash samples obtained via endoscopic ultrasound-guided fine-needle biopsy: Comparison with liquid biopsy of plasma in pancreatic cancer.

Objectives: Pancreatic cancer (PC) has a poor prognosis and limited treatment options. Liquid biopsy, which analyzes circulating tumor DNA (ctDNA) in blood, holds promise for precision medicine; however, low ctDNA detection rates pose challenges. This study aimed to investigate the utility of wash samples obtained via endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) as a liquid biopsy for PC.

Clinical and molecular biomarkers predicting response to PARP inhibitors in ovarian cancer.

Objective: To determine the useful biomarker for predicting the effects of poly-(ADP ribose)-polymerase (PARP) inhibitors in Japanese patients with ovarian cancer.

Methods: We collected clinical information and performed molecular biological analysis on 42 patients with ovarian, fallopian tube, and primary peritoneal carcinomas who received PARP inhibitors.

Results: Among the analyzed patients with ovarian cancer, 23.

Development of a molecular barcode detection system for pancreaticobiliary malignancies and comparison with next-generation sequencing.

Background: Obtaining sufficient tumor tissue for genomic profiling is challenging in pancreaticobiliary cancer (PBCA). We determined the utility of molecular barcoding (MB) of liquid biopsies (bile, duodenal fluid, and plasma) for highly sensitive genomic diagnosis and detection of druggable mutations for PBCA.

Methods: Two in-house panels of 60 genes (non-MB panel) and 21 genes using MB (MB panel) were used for the genomic analysis of 112 DNA samples from 20 PBCA patients.

Influence of formalin fixation duration on RNA quality and quantity from formalin-fixed paraffin-embedded hepatocellular carcinoma tissues.

Analyzing RNA samples from formalin-fixed paraffin-embedded (FFPE) tissues is essential for precision medicine. We investigated RNA quantity and quality from FFPE tumor tissues fixed in formalin for various times and compared sequencing metrics from next-generation sequencing (NGS). Hepatocellular carcinoma (HCC) tissues were fixed in 10% neutral buffered formalin (1-240 h) and FFPE blocks were prepared.

p53 Immunohistochemical Staining and TP53 Gene Mutations in Endometrial Cancer: Does Null Pattern Correlate With Prognosis?

Whether immunohistochemistry (IHC) of p53 accurately reflects the TP53 mutational status of endometrial carcinoma (EC) has not yet been established. This study aimed to clarify the relationship between p53 IHC and TP53 mutations in EC and to examine whether p53 IHC can be a more convenient prognostic marker than TP53 mutation in EC. We performed p53 IHC staining of EC samples obtained via surgery and genetic analyses using next-generation sequencing.

Genetic dissection of intratumor heterogeneity of PD-L1 expression in EGFR-mutated lung adenocarcinoma.

In this study, we investigated the association between PD-L1 expression in tumor cells and underlying genetic mutations, which was analyzed in detail using laser microdissection and next-generation sequencing analysis. To investigate whether driver mutations are involved in the background of PD-L1 expression, the EGFR major activating mutation was selected as the most frequent driver mutation. Surgical resection specimens were used to extract sufficient amounts of nucleic acids for analysis, and the high tumor proportion score (TPS:100%) and low (TPS: 0%) PD-L1-expressing parts of the tumor were each laser microdissected to examine the association between PD-L1 expression heterogeneity and genetic mutations within the same tumor.

Impact of the FilmArray Rapid Multiplex PCR Assay on Clinical Outcomes of Patients with Bacteremia.

Bacteremia is a serious disease with a reported mortality of 30%. Appropriate antibiotic use with a prompt blood culture can improve patient survival. However, when bacterial identification tests based on conventional biochemical properties are used, it takes 2 to 3 days from positive blood culture conversion to reporting the results, which makes early intervention difficult.

Nucleic Acid Quality Assessment is Critical to the Success of the Oncomine Dx Target Test for Lung Cancer.

Background And Objective: The Oncomine Dx Target Test (ODxTT) has been used as a companion diagnostic test for lung cancer. Here, we evaluated whether the amount of nucleic acid and the degree of RNA degradation are related to the success of the ODxTT.

Methods: This study included 223 samples from 218 patients with lung cancer.

Carcinogenic potential in regenerated mucosa after endoscopic resection of esophageal squamous cell carcinoma.

Background And Aim: Little is known about genetic mutations in the regenerated mucosa (RM) after endoscopic resection (ER) of esophageal carcinoma. Thus, this study investigates the status of genetic variation in RM after ER of esophageal squamous cell carcinoma (ESCC).

Methods: The study cohort included 19 patients with ESCC.

Comparison of genomic profiling of circulating tumor DNA in pancreaticobiliary malignancies in plasma and bile.

Background: Obtaining sufficient pancreaticobiliary tumor tissue for genomic profiling has limitations. Liquid biopsies using plasma do not provide sufficient sensitivity. Thus, this study aimed to determine the effectiveness of liquid biopsy between bile and plasma for identifying oncogenic and drug-matched mutations.

Validity of pathological diagnosis for early colorectal cancer in genetic background.

Background: This study aimed to investigate the validity of pathological diagnosis of early CRC (E-CRC) from the genetic background by comparing data of E-CRC to colorectal adenoma (CRA) and The Cancer Genome Atlas (TCGA) on advanced CRC (AD-CRC).

Methods: TCGA data on AD-CRC were studied in silico, whereas by next-generation sequencer, DNA target sequences were performed for endoscopically obtained CRA and E-CRC samples. Immunohistochemical staining of mismatch repair genes and methylation of MLH1 was also performed.

Paraganglioma with High Levels of Dopamine, Dopa Decarboxylase Suppression, Dopamine β-hydroxylase Upregulation and Intra-tumoral Melanin Accumulation: A Case Report with a Literature Review.

Object Exclusively dopamine-producing pheochromocytoma/paraganglioma (PPGL) is an extremely rare subtype. In this condition, intratumoral dopamine β-hydroxylase (DBH), which controls the conversion of norepinephrine from dopamine, is impaired, resulting in suppressed norepinephrine and epinephrine production. However, the rarity of this type of PPGL hampers the understanding of its pathophysiology.

Elucidation of genomic origin of synchronous endometrial and ovarian cancer (SEO) by genomic and microsatellite analysis.

Objective: Elucidation of clonal origin of synchronous endometrial and ovarian cancers (SEOs).

Methods: We reviewed 852 patients who diagnosed endometrial and/or ovarian cancer. Forty-five (5.

Deep targeted sequencing of cytological tumor cells using whole genome amplification.

Background: Genomic profiling in lung cancer is essential for precision medicine. Cytological specimens provide an alternative to formalin-fixed paraffin-embedded (FFPE) samples for comprehensive genomic analysis. However, this approach remains challenging when a limited number of tumor cells are available.

TP53-positive clones are responsible for drug-tolerant persister and recurrence of HER2-positive breast cancer.

Purpose: The prognosis of HER2-positive breast cancer has improved with the development of anti-HER2 therapies. In order to further improve the prognosis of HER2-positive breast cancer, it is essential to elucidate the cells that survive during the therapy (drug-tolerant persister DTP).

Methods: Of the 2022 breast cancer patients operated at our institution during 2004-2018, 240 (12%) had HER2-positive breast cancer.

Genomic profiling amplifies the utility of endoscopic ultrasound-guided fine needle biopsy by identifying clinically applicable druggable mutations in pancreatic cancer.

Background: Genomic profiling of tumors is available, but whether the small fragment obtained via endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) is sufficient for these examinations is unknown. Here we investigated whether EUS-FNB specimens are suitable for genomic profiling to identify oncogenic and drug-matched mutations.

Methods: We constructed a pancreatobiliary cancer panel for targeted panel sequencing that covered 60 significantly mutated genes and compared the results with those of whole-exome sequencing (WES).

Detection of actionable mutations in cytological specimens obtained by endoscopic ultrasound-guided fine needle aspiration with rapid onsite evaluation in pancreatic cancer.

Background: It is not clear whether archived cytological specimens (ACSs) obtained with endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) with rapid onsite evaluation (ROSE) can be used for genomic profiling of tumors. We used ACSs to perform genomic analysis of specimens to identify oncogenic and druggable mutations.

Methods: A panel of 60 significantly mutated genes specific to pancreatobiliary cancer was created and used for genomic analysis of 113 specimens of 44 formalin-fixed paraffin-embedded (FFPE) tissues and 69 ACSs obtained by EUS-FNA with ROSE were included.

Molecular analysis of ascitic fluid cytology reflects genetic changes of malignancies of the ovary equivalent to surgically resected specimens.

Background: The objective of this study was to identify the clinical utility of genomic analysis of ascitic fluid cytology (AC) in patients with epithelial ovarian cancer.

Methods: Targeted next-generation sequencing was used to analyze 66 samples from 33 patients who had ovarian (n = 23), fallopian tube (n = 2), and peritoneal (n = 8) carcinoma, and the concordance rate of molecular profiles was compared between surgically resected, formalin-fixed, paraffin-embedded (FFPE) tissues and AC samples.

Results: In total, 159 mutations were identified (54 oncogenic mutations and 105 nononcogenic mutations) in 66 DNA samples (33 FFPE tissues and 33 AC samples) from 33 patients.

Simple IHC reveals complex MMR alternations than PCR assays: Validation by LCM and next-generation sequencing.

Evaluation of the status of mismatch repair (MMR) in tumors is crucial for determining the application of immune checkpoint inhibitors (ICIs). Conventional PCR (MSI-PCR) is the gold standard for confirming the MMR status. However, it requires visual confirmation and presents difficulties in determining MMR status.

Loss of Heterozygosity Induces De Novo SCLC Formation in EGFR-Mutated Lung Adenocarcinoma: A Case Report.

SCLC transformation in EGFR-mutated lung adenocarcinoma is one of the major phenotypic changes that is observed during the resistance to EGFR tyrosine kinase inhibitors. However, the mechanism of this transformation remains unclear. In this study, we found a small de novo SCLC component in surgically resected specimens of EGFR-mutated lung adenocarcinoma before EGFR tyrosine kinase inhibitor treatment.