Microenvironment-induced restoration of cohesive growth associated with focal activation of P-cadherin expression in lobular breast carcinoma metastatic to the colon.

Invasive lobular carcinoma (ILC) is a special breast cancer type characterized by noncohesive growth and E-cadherin loss. Focal activation of P-cadherin expression in tumor cells that are deficient for E-cadherin occurs in a subset of ILCs. Switching from an E-cadherin deficient to P-cadherin proficient status (EPS) partially restores cell-cell adhesion leading to the formation of cohesive tubular elements.

Noninferiority of Artificial Intelligence-Assisted Analysis of Ki-67 and Estrogen/Progesterone Receptor in Breast Cancer Routine Diagnostics.

Image analysis assistance with artificial intelligence (AI) has become one of the great promises over recent years in pathology, with many scientific studies being published each year. Nonetheless, and perhaps surprisingly, only few image AI systems are already in routine clinical use. A major reason for this is the missing validation of the robustness of many AI systems: beyond a narrow context, the large variability in digital images due to differences in preanalytical laboratory procedures, staining procedures, and scanners can be challenging for the subsequent image analysis.

Classification of Pancreatic Ductal Adenocarcinoma Using MALDI Mass Spectrometry Imaging Combined with Neural Networks.

Despite numerous diagnostic and therapeutic advances, pancreatic ductal adenocarcinoma (PDAC) has a high mortality rate, and is the fourth leading cause of cancer death in developing countries. Besides its increasing prevalence, pancreatic malignancies are characterized by poor prognosis. Omics technologies have potential relevance for PDAC assessment but are time-intensive and relatively cost-intensive and limited by tissue heterogeneity.

Inter-observer agreement for the histological diagnosis of invasive lobular breast carcinoma.

Invasive lobular breast carcinoma (ILC) is the second most common breast carcinoma (BC) subtype and is mainly driven by loss of E-cadherin expression. Correct classification of BC as ILC is important for patient treatment. This study assessed the degree of agreement among pathologists for the diagnosis of ILC.

Classification of Inflammatory Bowel Disease from Formalin-Fixed, Paraffin-Embedded Tissue Biopsies via Imaging Mass Spectrometry.

Purpose: Discrimination between ulcerative colitis (UC) and Crohn's disease (CD) by histologic features alone can be challenging and often leads to inaccurate initial diagnoses in inflammatory bowel disease (IBD) patients. This is mostly due to an overlap of clinical and histologic features. However, exact diagnosis is not only important for patient treatment but it also has a socioeconomic impact.

Isolated Intraocular Rosai-Dorfman Disease.

Background/aims: To report a case of Rosai-Dorfman disease (RDD) presenting as a solitary, choroidal mass, initially suspicious for uveal melanoma, in a 72-year-old woman.

Methods: Retrospective case report of a single patient.

Results: A 72-year-old woman presented with sudden vision loss in the right eye.

The EndoRotor(®): endoscopic mucosal resection system for non-thermal and rapid removal of esophageal, gastric, and colonic lesions: initial experience in live animals.

Background And Study Aims: The EndoRotor(®) is a novel, non-thermal, automated mechanical endoscopic resection system designed to remove benign mucosal neoplastic tissue throughout the gastrointestinal tract. It uses suction pressure to pull in mucosa and rapidly and precisely cut it while automatically transporting the samples to a collection trap for later histologic evaluation.

Patients And Methods: To study the technical properties and therapeutic potential of this new tool, we performed multiple upper and lower gastrointestinal endoscopic mucosal resections in three healthy live pigs.

Multicenter randomized controlled trial comparing the performance of 22 gauge versus 25 gauge EUS-FNA needles in solid masses.

Background And Aims: Few randomized studies have assessed the clinical performance of 25-gauge (25G) needles compared with 22-gauge (22G) needles during endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) biopsy of intra-abdominal lesions. We aimed to compare the diagnostic yield, as well as performance characteristics of 22G versus 25G EUS biopsy needles by determining their diagnostic capabilities, the number of needle passes as well as cellularity of aspirated tissue specimen.

Methods: The study is a prospective, randomized, multicenter study.

Impact of single-dose application of TGF-β, copper peptide, stanozolol and ascorbic acid in hydrogel on midline laparatomy wound healing in a diabetic mouse model.

Despite numerous advances and improvements in surgical techniques the incidence of incisional hernias after laparotomy remains high. The aim of this study was to investigate possible effects of single application of ascorbic acid, stanozolol, a synthetic anabolic steroid, copper peptide and transforming growth factor-β (TGF-β) on laparotomy wound healing in an incisional wound model in diabetic mice. After diabetes induction with streptozotozin in Balb-c mice, midline laparatomies were carried out.

Priming with a combination of proangiogenic growth factors enhances wound healing in streptozotocin-induced diabetes in mice.

Background: Numerous proangiogenic growth factors have been shown to improve impaired wound healing. This study evaluated the effects of subcutaneous pretreatment with a combination of proangiogenic growth factors on wound closure, mechanical properties, vessel density, and morphology.

Methods: Thirty-six Balb/c mice with streptozotocin-induced diabetes were divided into 3 groups.

Priming with a combination of proangiogenic growth factors improves wound healing in normoglycemic mice.

Growth factors and/or angiogenic factors are supposed to improve wound healing. The aim of our study was to evaluate the effects of subcutaneous pretreatment with combinatory proangiogenic factors on wound closure, mechanical properties, vessel density and morphology. Twenty-eight Balb/c mice were divided equally into two groups.

MALDI imaging as a specific diagnostic tool for routine cervical cytology specimens.

Cervical squamous cell carcinoma (SCC) is among the most common malignancies in women worldwide. In developed countries routine cytology screening has dramatically reduced SCC mortality within the last three decades. High risk (HR) human papilloma virus (HPV) infection is the main causal factor in nearly 100% of invasive SCCs, in most cases of low grade squamous intraepithelial lesion (LSIL) and in nearly all cases of high grade squamous intraepithelial lesion (HSIL).

Application of MALDI imaging for the diagnosis of classical Hodgkin lymphoma.

Hodgkin lymphoma (HL) is a distinctive lymphoma subtype characterized by rareness of tumor cells [Hodgkin's and Reed-Sternberg (HRS) cells in classical HL and lymphocytic and histiocytic cells in lymphocyte predominant HL] as well as the vast majority of the surrounding inflammatory-like cellular infiltrate. Still the onset of this highly variable disease is not completely understood. Proteome analysis can lead to the identification of potential proteins capable of elucidating malignant growth and survival in HL.

Impact of combinatory growth factor application on rabbit Achilles tendon injury with operative versus conservative treatment: a pilot study.

Acute Achilles tendon (AT) rupture is a common injury with a comparatively high complication rate. Presently, surgical treatments compete with nonoperative treatment modalities. The aim of this study was to elucidate the possible beneficial effects of short-term combinatory application of growth factors on tendon healing during operative or conservative treatment.

Polymorphisms of the apoptosis-associated gene DP1L1 (deleted in polyposis 1-like 1) in colon cancer and inflammatory bowel disease.

Purpose: The deleted-in-polyposis1-like1 (DP1L1) gene displays pro-apoptotic activity and was proposed to be a tumor suppressor. It locates on chromosome 19p13.3, which harbors the locus for Peutz-Jeghers-Syndrome and is deleted in various tumors.

Mutational analysis of the BRAF, RAS and EGFR genes in human adrenocortical carcinomas.

The serine/threonine kinase B-Raf plays a key role in the Ras/Raf/MEK/ERK pathway that relays extracellular signals for cell proliferation and survival. Several types of human malignancies harbor activating BRAF mutations, most frequently a V600E substitution. The epidermal growth factor receptor (EGFR), a transmembrane tyrosine kinase (TK) receptor that mediates proliferation and survival signaling, is expressed in a wide variety of normal and neoplastic tissues.

Activation of Wnt signalling in stroma from pancreatic cancer identified by gene expression profiling.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by an abundant desmoplastic stroma. Interactions between cancer and stromal cells play a critical role in tumour invasion, metastasis and chemoresistance. Therefore, we hypothesized that gene expression profile of the stromal components of pancreatic carcinoma is different from chronic pancreatitis and reflects the interaction with the tumour.

The human trithorax protein hASH2 functions as an oncoprotein.

Regulation of chromatin is an important aspect of controlling promoter activity and gene expression. Posttranslational modifications of core histones allow proteins associated with gene transcription to access chromatin. Closely associated with promoters of actively transcribed genes, trimethylation of histone H3 at lysine 4 (H3K4me3) is a core histone mark set by several protein complexes.

Proteomic analysis of mucosal preparations from patients with ulcerative colitis.

Proteomic profiling with the identification of molecular signatures is a powerful tool in the study of pathogenesis, and may allow us to predict the prognosis of disease states. In this study, mucosa/submucosa from the colonic resections of five patients with ulcerative colitis (UC) who had undergone colonic resection were microdisected. Proteins were separated by two-dimensional (2D) polyacrylamide gel electrophoresis.

Lessons from a patient with an unusual hepatic overlap syndrome.

Background: A 24-year-old white male was diagnosed as having Crohn's disease by clinical, endoscopic and histological assessments, and long-term remission was successfully induced with short-course prednisolone. While the Crohn's disease was still in remission, the patient presented with cholestasis and hyperbilirubinemia but normal alanine aminotransferase levels, negative results for serological tests for infectious causes of hepatopathy and normal gamma-globulin levels.

Investigations: Repeated laboratory and serological tests, ultrasonography, endoscopic retrograde cholangiopancreatographies, CT scan, magnetic resonance cholangiopancreatography and liver biopsies.

Identifying prostate carcinoma by MALDI-Imaging.

Prostate cancer has become one of the most common malignancies worldwide. Although lacking in specificity its diagnosis is still based partially on the serum-based test for prostate-specific antigen. As its pathogenesis has not yet been deciphered, the ongoing search for new and more reliable biomarkers remains a challenge to stratify disease onset and progression.

Tumour-stroma interactions between metastatic prostate cancer cells and fibroblasts.

Previous work has shown the importance of tumour-stroma interactions for prostate cancer development at the primary site. The aim of the present study was to find out whether evidence can be found for a tumour-stroma cross- talk also between metastatic prostate cancer cell lines and non-prostatic stromal fibroblasts which are encountered by metastatic cells at most sites. We addressed this issue in cell culture systems using 3 metastatic human prostate cancer cell lines (LnCaP, PC-3 and DU-145) on the one hand, and a human fibroblast line (HFF, human foreskin fibroblasts) on the other.

Cellular retinoic acid-binding protein 2 is down-regulated in prostate cancer.

Prostate cancer is among the most frequent tumours in industrialized nations and many questions remain open concerning the molecular events underlying its development and progression. In the present study we have combined cDNA array hybridization to laser-assisted microdissection (LAM) in order to investigate differences in gene expression between epithelial and stromal cells of prostate cancer and normal peripheral prostate tissue. Results have been verified for selected candidate genes by quantitative real-time RT-PCR.

Mice transgenic for NPM-ALK develop non-Hodgkin lymphomas.

Background: The t(2;5)(p23;q35) translocation is associated with a high percentage of anaplastic large-cell lymphomas (ALCL) of T- or null-cell phenotype. The translocation produces an 80 kDa hyperphosphorylated chimeric protein (p80) derived from the fusion of the anaplastic lymphoma kinase (ALK) with nucleophosmin (NPM). The NPM-ALK chimeric protein is an activated tyrosine kinase that has been shown to be a potent oncogene and presumably plays a causative role in lymphomagenesis.

Diagnostic and prognostic information in prostate cancer with the help of a small set of hypermethylated gene loci.

Purpose: Our study was designed to evaluate promoter CpG island hypermethylation in the diagnosis and prognosis of prostate cancer.

Experimental Design: Primary prostate cancers from 53 patients, pelvic lymph nodes, noncancerous prostate tissues, and prostate cell lines were analyzed. Real-time methylation-specific PCR was used to identify CpG island hypermethylation at five promising gene loci (i.