Genomic signatures of past and present chromosomal instability in Barrett's esophagus and early esophageal adenocarcinoma.

The progression of precancerous lesions to malignancy is often accompanied by increasing complexity of chromosomal alterations but how these alterations arise is poorly understood. Here we perform haplotype-specific analysis of chromosomal copy-number evolution in the progression of Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC) on multiregional whole-genome sequencing data of BE with dysplasia and microscopic EAC foci. We identify distinct patterns of copy-number evolution indicating multigenerational chromosomal instability that is initiated by cell division errors but propagated only after p53 loss.

Accuracy of definitive rapid onsite evaluation cytopathology diagnoses: Assessment of potentially critical diagnoses as a quality assurance measure.

Introduction: Intraprocedural rapid onsite evaluation (ROSE) of cytology specimens enhances cytopathology practice. More recently, ROSE diagnoses, like frozen section (FS) diagnoses, have guided immediate clinical decisions. In this study, we evaluated the diagnostic accuracy of definitive ROSE diagnoses in our quality assurance system over a 52-month period.

Use of p53 immunohistochemistry in conjunction with routine histology improves risk stratification of patients with Barrett's oesophagus during routine clinical care.

Aims: Abnormal p53 protein expression detected by immunohistochemistry (IHC) in Barrett's oesophagus (BO) is reported to be a prognostic biomarker for progression to high-grade dysplasia (HGD) or oesophageal adenocarcinoma (OAC). We evaluated our use of p53 IHC for patients with BO under surveillance from 2010 to 2016 in a single academic institution.

Methods And Results: We identified 78 patients under surveillance for BO who had biopsies evaluated for abnormal p53 expression in conjunction with routine histology and 892 patients who had histological evaluation alone.

Independent Blinded Validation of a Tissue Systems Pathology Test to Predict Progression in Patients With Barrett's Esophagus.

Introduction: A risk prediction test was previously validated to predict progression to high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus (BE). The aim of our study was to independently validate this test to predict the risk of progression to HGD/EAC in BE patients with nondysplastic (ND), indefinite for dysplasia and low-grade dysplasia (LGD).

Methods: A single-blinded, case-control study was conducted to stratify patients with BE as low, intermediate, or high risk for progression to HGD/EAC within 5 years using a previously described risk prediction test.

Loss of ARID1A expression is associated with DNA mismatch repair protein deficiency and favorable prognosis in advanced stage surgically resected esophageal adenocarcinoma.

Esophageal adenocarcinoma often presents at an advanced stage and has a dismal prognosis. Current prognostic markers have limited utility. ARID1A is implicated as a tumor suppressor gene in esophageal adenocarcinoma.

High-resolution genomic alterations in Barrett's metaplasia of patients who progress to esophageal dysplasia and adenocarcinoma.

The main risk factor for esophageal dysplasia and adenocarcinoma (DAC) is Barrett's esophagus (BE), characterized by intestinal metaplasia. The critical genomic mechanisms that lead to progression of nondysplastic BE to DAC remain poorly understood and require analyses of longitudinal patient cohorts and high-resolution assays. We tested BE tissues from 74 patients, including 42 nonprogressors from two separate groups of 21 patients each and 32 progressors (16 in a longitudinal cohort before DAC/preprogression-BE and 16 with temporally concurrent but spatially separate DAC/concurrent-BE).

Low-grade dysplasia diagnosis ratio and progression metrics identify variable Barrett's esophagus risk stratification proficiency in independent pathology practices.

Background And Aims: The diagnosis of low-grade dysplasia (LGD) in Barrett's esophagus (BE) is subject to substantial interobserver variation. Our central aim in this study is to compare independent pathology practices using objective measures of BE risk stratification proficiency, including frequency of diagnosis and rate of progression, with high-grade dysplasia (HGD) or adenocarcinoma (EAC) after the first diagnosis of LGD.

Methods: We retrospectively evaluated over 29,000 endoscopic biopsy cases to identify 4734 patients under endoscopic biopsy surveillance for BE in a healthcare system with multiple independent pathology practices: a subspecialized GI pathology group (SSGI; 162 BE cases per pathologist annually), 3 high BE volume general surgical pathology practices (GSPs; >50 BE cases per pathologist annually), and multiple low BE volume GSPs (10.

Detection of Mutations in Barrett's Esophagus Before Progression to High-Grade Dysplasia or Adenocarcinoma.

Background & Aims: Barrett's esophagus (BE) is the greatest risk factor for esophageal adenocarcinoma (EAC), but only a small proportion of patients with BE develop cancer. Biomarkers might be able to identify patients at highest risk of progression. We investigated genomic differences in surveillance biopsies collected from patients whose BE subsequently progressed compared to patients whose disease did not progress.

Extreme chromosome 17 copy number instability is a prognostic factor in patients with gastroesophageal adenocarcinoma: A retrospective cohort study.

Gastric and esophageal cancers frequently show genomic instability and aneuploidy. Chromosomal copy number instability (CIN) is a form of genomic instability that exerts pleiotropic effects on cellular biology and is a source of genetic heterogeneity in a population of cells. CIN results in cell-to-cell variation in chromosome copy number which can be detected and quantified by fluorescence in situ hybridization (FISH).

The Use of Ancillary Stains in the Diagnosis of Barrett Esophagus and Barrett Esophagus-associated Dysplasia: Recommendations From the Rodger C. Haggitt Gastrointestinal Pathology Society.

Barrett esophagus (BE) is a known risk factor for the development of esophageal adenocarcinoma. Pathologists play a critical role in confirming the diagnosis of BE and BE-associated dysplasia. As these diagnoses are not always straightforward on routine hematoxylin and eosin-stained slides, numerous ancillary stains have been used in an attempt to help pathologists confirm the diagnosis.

5-Fluorouracil upregulates cell surface B7-H1 (PD-L1) expression in gastrointestinal cancers.

Background: Resistance to chemotherapy is a major obstacle in the effective treatment of cancer patients. B7-homolog 1, also known as programmed death ligand-1 (PD-L1), is an immunoregulatory protein that is overexpressed in several human cancers. Interaction of B7-H1 with programmed death 1 (PD-1) prevents T-cell activation and proliferation, sequestering the T-cell receptor from the cell membrane, inducing T-cell apoptosis, thereby leading to cancer immunoresistance.

A Tissue Systems Pathology Test Detects Abnormalities Associated with Prevalent High-Grade Dysplasia and Esophageal Cancer in Barrett's Esophagus.

Background: There is a need for improved tools to detect high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus. In previous work, we demonstrated that a 3-tier classifier predicted risk of incident progression in Barrett's esophagus. Our aim was to determine whether this risk classifier could detect a field effect in nondysplastic (ND), indefinite for dysplasia (IND), or low-grade dysplasia (LGD) biopsies from Barrett's esophagus patients with prevalent HGD/EAC.

A Tissue Systems Pathology Assay for High-Risk Barrett's Esophagus.

Background: Better methods are needed to predict risk of progression for Barrett's esophagus. We aimed to determine whether a tissue systems pathology approach could predict progression in patients with nondysplastic Barrett's esophagus, indefinite for dysplasia, or low-grade dysplasia.

Methods: We performed a nested case-control study to develop and validate a test that predicts progression of Barrett's esophagus to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC), based upon quantification of epithelial and stromal variables in baseline biopsies.

Morphological and molecular approach to synchronous non-small cell lung carcinomas: impact on staging.

Distinction between multiple primary cancers and intrapulmonary metastases in patients with synchronous multifocal lung cancer can be challenging. Histological and genotypic assessment of multifocal lung tumors have been suggested to influence the staging. The aim of this study was to determine the role of morphology and genotype in staging of surgically treated multifocal non-small cell lung carcinoma.

A Model Based on Pathologic Features of Superficial Esophageal Adenocarcinoma Complements Clinical Node Staging in Determining Risk of Metastasis to Lymph Nodes.

Background & Aims: It is important to identify superficial (T1) gastroesophageal adenocarcinomas (EAC) that are most or least likely to metastasize to lymph nodes, to select appropriate therapy. We aimed to develop a risk stratification model for metastasis of superficial EAC to lymph nodes using pathologic features of the primary tumor.

Methods: We collected pathology data from 210 patients with T1 EAC who underwent esophagectomy from 1996 through 2012 on factors associated with metastasis to lymph nodes (tumor size, grade, angiolymphatic invasion, and submucosal invasion).

TissueCypher(™): A systems biology approach to anatomic pathology.

Background: Current histologic methods for diagnosis are limited by intra- and inter-observer variability. Immunohistochemistry (IHC) methods are frequently used to assess biomarkers to aid diagnoses, however, IHC staining is variable and nonlinear and the manual interpretation is subjective. Furthermore, the biomarkers assessed clinically are typically biomarkers of epithelial cell processes.

Paired exome analysis of Barrett's esophagus and adenocarcinoma.

Barrett's esophagus is thought to progress to esophageal adenocarcinoma (EAC) through a stepwise progression with loss of CDKN2A followed by TP53 inactivation and aneuploidy. Here we present whole-exome sequencing from 25 pairs of EAC and Barrett's esophagus and from 5 patients whose Barrett's esophagus and tumor were extensively sampled. Our analysis showed that oncogene amplification typically occurred as a late event and that TP53 mutations often occurred early in Barrett's esophagus progression, including in non-dysplastic epithelium.

The revised American Joint Committee on Cancer staging system (7th edition) improves prognostic stratification after minimally invasive esophagectomy for esophagogastric adenocarcinoma.

Background: Staging for esophagogastric adenocarcinoma lacked sufficient prognostic accuracy and was revised. We compared survival prognostication between American Joint Committee on Cancer (AJCC) 6th and 7th editions.

Methods: We abstracted data for 836 patients who underwent minimally invasive esophagectomy for esophagogastric adenocarcinoma (n = 256 neoadjuvant).

Epithelial PD-L2 Expression Marks Barrett's Esophagus and Esophageal Adenocarcinoma.

Esophageal adenocarcinoma is an increasingly common disease with a dismal 5-year survival rate of 10% to 15%. In the first systematic evaluation of the PD-1 pathway in esophageal adenocarcinoma, we identify expression of PD-L2 in cancer cells in 51.7% of esophageal adenocarcinomas.

Smad4 loss in esophageal adenocarcinoma is associated with an increased propensity for disease recurrence and poor survival.

Previously regarded as a rare neoplasm, the incidence of esophageal adenocarcinoma has risen rapidly in recent decades. It is often discovered late in the disease process and has a dismal prognosis. Current prognostic markers including clinical, radiographic, and histopathologic findings have limited utility and do not consider the biology of this deadly disease.

Undifferentiated carcinoma of the esophagus: a clinicopathological study of 16 cases.

Undifferentiated carcinoma of the esophagus is a rare histologic variant of esophageal carcinoma. Using criteria based on studies of undifferentiated carcinomas arising at other sites, we have collected 16 cases of resected esophageal undifferentiated carcinomas. Patients ranged in age from 39 to 84 years (mean, 65.

Evaluation of a 4-protein serum biomarker panel-biglycan, annexin-A6, myeloperoxidase, and protein S100-A9 (B-AMP)-for the detection of esophageal adenocarcinoma.

Background: Esophageal adenocarcinoma (EAC) is associated with a dismal prognosis. The identification of cancer biomarkers can advance the possibility for early detection and better monitoring of tumor progression and/or response to therapy. The authors present results from the development of a serum-based, 4-protein (biglycan, myeloperoxidase, annexin-A6, and protein S100-A9) biomarker panel for EAC.

GNAS is frequently mutated in both low-grade and high-grade disseminated appendiceal mucinous neoplasms but does not affect survival.

We analyzed a series of 55 disseminated appendiceal mucinous neoplasms treated at our institution for GNAS and KRAS mutations in an attempt to correlate mutation status with clinicopathological findings and patient survival. GNAS mutations (p.R201H, c.

Tumor budding is associated with an increased risk of lymph node metastasis and poor prognosis in superficial esophageal adenocarcinoma.

The treatment approach for superficial (stage T1) esophageal adenocarcinoma critically depends on the pre-operative assessment of metastatic risk. Part of that assessment involves evaluation of the primary tumor for pathologic characteristics known to predict nodal metastasis: depth of invasion (intramucosal vs submucosal), angiolymphatic invasion, tumor grade, and tumor size. Tumor budding is a histologic pattern that is associated with poor prognosis in early-stage colorectal adenocarcinoma and a predictor of nodal metastasis in T1 colorectal adenocarcinoma.