Rare subclonal sequencing of breast cancers indicates putative metastatic driver mutations are predominately acquired after dissemination.

Background: Evolutionary models of breast cancer progression differ on the extent to which metastatic potential is pre-encoded within primary tumors. Although metastatic recurrences often harbor putative driver mutations that are not detected in their antecedent primary tumor using standard sequencing technologies, whether these mutations were acquired before or after dissemination remains unclear.

Methods: To ascertain whether putative metastatic driver mutations initially deemed specific to the metastasis by whole exome sequencing were, in actuality, present within rare ancestral subclones of the primary tumors from which they arose, we employed error-controlled ultra-deep sequencing (UDS-UMI) coupled with FFPE artifact mitigation by uracil-DNA glycosylase (UDG) to assess the presence of 132 "metastasis-specific" mutations within antecedent primary tumors from 21 patients.

Prognostic correlations with the microbiome of breast cancer subtypes.

Alterations to the natural microbiome are linked to different diseases, and the presence or absence of specific microbes is directly related to disease outcomes. We performed a comprehensive analysis with unique cohorts of the four subtypes of breast cancer (BC) characterized by their microbial signatures, using a pan-pathogen microarray strategy. The signature (includes viruses, bacteria, fungi, and parasites) of each tumor subtype was correlated with clinical data to identify microbes with prognostic potential.

Computationally Derived Cribriform Area Index from Prostate Cancer Hematoxylin and Eosin Images Is Associated with Biochemical Recurrence Following Radical Prostatectomy and Is Most Prognostic in Gleason Grade Group 2.

Background: The presence of invasive cribriform adenocarcinoma (ICC), an expanse of cells containing punched-out lumina uninterrupted by stroma, in radical prostatectomy (RP) specimens has been associated with biochemical recurrence (BCR). However, ICC identification has only moderate inter-reviewer agreement.

Objective: To investigate quantitative machine-based assessment of the extent and prognostic utility of ICC, especially within individual Gleason grade groups.

Stable and discriminating features are predictive of cancer presence and Gleason grade in radical prostatectomy specimens: a multi-site study.

Site variation in fixation, staining, and scanning can confound automated tissue based image classifiers for disease characterization. In this study we incorporated stability into four feature selection methods for identifying the most robust and discriminating features for two prostate histopathology classification tasks. We evaluated 242 morphology features from N = 212 prostatectomy specimens from four sites for automated cancer detection and grading.

Accurate and reproducible invasive breast cancer detection in whole-slide images: A Deep Learning approach for quantifying tumor extent.

With the increasing ability to routinely and rapidly digitize whole slide images with slide scanners, there has been interest in developing computerized image analysis algorithms for automated detection of disease extent from digital pathology images. The manual identification of presence and extent of breast cancer by a pathologist is critical for patient management for tumor staging and assessing treatment response. However, this process is tedious and subject to inter- and intra-reader variability.

Evaluating stability of histomorphometric features across scanner and staining variations: prostate cancer diagnosis from whole slide images.

Quantitative histomorphometry (QH) is the process of computerized feature extraction from digitized tissue slide images to predict disease presence, behavior, and outcome. Feature stability between sites may be compromised by laboratory-specific variables including dye batch, slice thickness, and the whole slide scanner used. We present two new measures, preparation-induced instability score and latent instability score, to quantify feature instability across and within datasets.

Self-renewal of CD133(hi) cells by IL6/Notch3 signalling regulates endocrine resistance in metastatic breast cancer.

The mechanisms of metastatic progression from hormonal therapy (HT) are largely unknown in luminal breast cancer. Here we demonstrate the enrichment of CD133(hi)/ER(lo) cancer cells in clinical specimens following neoadjuvant endocrine therapy and in HT refractory metastatic disease. We develop experimental models of metastatic luminal breast cancer and demonstrate that HT can promote the generation of HT-resistant, self-renewing CD133(hi)/ER(lo)/IL6(hi) cancer stem cells (CSCs).

Computer-extracted Features Can Distinguish Noncancerous Confounding Disease from Prostatic Adenocarcinoma at Multiparametric MR Imaging.

Purpose: To determine the best features to discriminate prostate cancer from benign disease and its relationship to benign disease class and cancer grade.

Materials And Methods: The institutional review board approved this study and waived the need for informed consent. A retrospective cohort of 70 patients (age range, 48-70 years; median, 62 years), all of whom were scheduled to undergo radical prostatectomy and underwent preoperative 3-T multiparametric magnetic resonance (MR) imaging, including T2-weighted, diffusion-weighted, and dynamic contrast material-enhanced imaging, were included.

Identifying in vivo DCE MRI markers associated with microvessel architecture and gleason grades of prostate cancer.

Background: To identify computer extracted in vivo dynamic contrast enhanced (DCE) MRI markers associated with quantitative histomorphometric (QH) characteristics of microvessels and Gleason scores (GS) in prostate cancer.

Methods: This study considered retrospective data from 23 biopsy confirmed prostate cancer patients who underwent 3 Tesla multiparametric MRI before radical prostatectomy (RP). Representative slices from RP specimens were stained with vascular marker CD31.

Risk factors for gyrA and parC mutations in Pseudomonas aeruginosa.

Objective: The major mechanism of fluoroquinolone (FQ) resistance in Pseudomonas aeruginosa (PSA) is modification of target proteins in DNA gyrase and topoisomerase IV, most commonly the gyrA and parC subunits. The objective of this study was to determine risk factors for PSA with and without gyrA or parC mutations.

Design: Case-case-control study

Setting: Two adult academic acute-care hospitals

Patients: Case 1 study participants had a PSA isolate on hospital day 3 or later with any gyrA or parC mutation; case 2 study participants had a PSA isolate on hospital day 3 or later without these mutations.

Supervised multi-view canonical correlation analysis (sMVCCA): integrating histologic and proteomic features for predicting recurrent prostate cancer.

In this work, we present a new methodology to facilitate prediction of recurrent prostate cancer (CaP) following radical prostatectomy (RP) via the integration of quantitative image features and protein expression in the excised prostate. Creating a fused predictor from high-dimensional data streams is challenging because the classifier must 1) account for the "curse of dimensionality" problem, which hinders classifier performance when the number of features exceeds the number of patient studies and 2) balance potential mismatches in the number of features across different channels to avoid classifier bias towards channels with more features. Our new data integration methodology, supervised Multi-view Canonical Correlation Analysis (sMVCCA), aims to integrate infinite views of highdimensional data to provide more amenable data representations for disease classification.

Co-occurring gland angularity in localized subgraphs: predicting biochemical recurrence in intermediate-risk prostate cancer patients.

Quantitative histomorphometry (QH) refers to the application of advanced computational image analysis to reproducibly describe disease appearance on digitized histopathology images. QH thus could serve as an important complementary tool for pathologists in interrogating and interpreting cancer morphology and malignancy. In the US, annually, over 60,000 prostate cancer patients undergo radical prostatectomy treatment.

A unique pancreatic tumor with exclusive hepatocytic differentiation.

Only 7 cases of pancreatic tumor with hepatocytic differentiation have been reported in the literature, including 6 cases of hepatoid carcinoma and one case of hepatoid adenoma. Diagnosis of hepatoid carcinoma depends on recognition of characteristic histological features, supported by other evidence linked to hepatic lineage including alpha-fetoprotein production, positive immunoreactivity to liver synthesized proteins, and in situ hybridization detection of albumin mRNA. In addition, a synchronous focus of carcinoma arising in pancreatic ducts, islet cells, or acinar cells is essential.