Sensitive and broadly applicable residual disease detection in acute myeloid leukemia using flow cytometry-based leukemic cell enrichment followed by mutational profiling.

Persistent measurable residual disease (MRD) is an increasingly important prognostic marker in acute myeloid leukemia (AML). Currently, MRD is determined by multi-parameter flow cytometry (MFC) or PCR-based methods detecting leukemia-specific fusion transcripts and mutations. However, while MFC is highly operator-dependent and difficult to standardize, PCR-based methods are only available for a minority of AML patients.

Residual disease detection using targeted parallel sequencing predicts relapse in cytogenetically normal acute myeloid leukemia.

Despite achieving complete remission after intensive therapy, most patients with cytogenetically normal (CN) AML relapse due to the persistence of submicroscopic residual disease. In this pilot study, we hypothesized that detection of leukemia-specific mutations following consolidation treatment using a targeted parallel sequencing approach predicts relapse. We included 34 AML patients of whom diagnostic material and remission bone marrow slides after at least one cycle of consolidation were available.

HPV-negative penile squamous cell carcinoma: disruptive mutations in the TP53 gene are common.

The majority of penile squamous cell carcinomas is caused by transforming human papilloma virus (HPV) infection. The etiology of HPV-negative cancers is unclear, but TP53 mutations have been implicated. Archival tissues of 108 invasive squamous cell carcinoma from a single pathology institution in a low-incidence area were analyzed for HPV-DNA and p16 overexpression and for TP53 mutations by ion torrent next-generation sequencing.

Signal Transducer and Activator of Transcription 1 (STAT1) Knock-down Induces Apoptosis in Malignant Pleural Mesothelioma.

Malignant pleural mesothelioma (MPM) is the most common primary tumor of the pleura. Its incidence is still increasing in Europe and the prognosis remains poor. We investigated the oncogenic function of signal transducer and activator of transcription 1 (STAT1) in MPM in more detail.

Mutational dichotomy in desmoplastic malignant melanoma corroborated by multigene panel analysis.

Desmoplastic malignant melanoma is a distinct melanoma entity histologically subtyped into mixed and pure forms due to significantly reduced lymph node metastases in the pure form. Recent reports investigating common actionable driver mutations have demonstrated a lack of BRAF, NRAS, and KIT mutation in pure desmoplastic melanoma. In search for alternative driver mutations next generation amplicon sequencing for hotspot mutations in 50 genes cardinal to tumorigenesis was performed and in addition the RET G691S polymorphism was investigated.

Usual interstitial pneumonia and smoking-related interstitial fibrosis display epithelial to mesenchymal transition in fibroblastic foci.

Background: Fibroblastic foci (FF) are a major histological feature of usual interstitial pneumonia (UIP) in idiopathic pulmonary fibrosis (IPF) and collagen vascular diseases (non-IPF). In addition, FF are occasionally associated with smoking-related interstitial fibrosis (SRIF). Recent studies have suggested a role for epithelial to mesenchymal transition (EMT) in pulmonary fibrogenesis.

Signal transducer and activator of transcription 1 (STAT1) acts like an oncogene in malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is the most common primary tumor of the pleura. Its incidence is increasing in Europe and the prognosis remains poor. We compared epithelioid MPM in short and long survivors, and identified signal transducer and activator of transcription 1 (STAT1) as probably being responsible for antiapoptotic signaling and chemoresistance.

BAP1 protein is a progression factor in malignant pleural mesothelioma.

Human malignant pleural mesothelioma (MPM) is an aggressive cancer due to former asbestos exposure with little knowledge about prognostic factors of outcome and resistance to conventional therapy. BRCA1-associated protein 1 (BAP1) is a tumor suppressor gene that is frequently lost in MPM. Germline mutations of BAP1 predispose to several different tumors including malignant mesothelioma.

Reduced folate carrier and folylpolyglutamate synthetase, but not thymidylate synthase predict survival in pemetrexed-treated patients suffering from malignant pleural mesothelioma.

Background: Malignant mesothelioma is a highly aggressive tumor arising from mesothelial-lined surfaces, most often in the pleura cavities. Antifolates belong to the most effective cytotoxic drugs for malignant pleural mesothelioma (MPM) treatment. Pemetrexed is an antifolate inhibiting different folate pathway genes (thymidylate synthase [TS], dihydrofolate reductase, glycinamide ribonucleotide formyltransferase [GARFT], and aminoimidazole carboxamide ribonucleotide formyltransferase, [AICARFT]).

Chromosomal aberrations as detected by array comparative genomic hybridization in early low-grade intraepithelial neoplasias of the breast.

Aims: Low-grade flat ductal intraepithelial neoplasia (DIN1a, flat epithelial atypia) is one of the earliest morphologically recognizable neoplastic lesions of the breast. Frequently, it occurs concomitantly with lobular intraepithelial neoplasia (LIN). We aimed to elucidate chromosomal aberrations in these early neoplastic breast lesions with the use of array comparative genomic hybridization analysis.

Evaluation of formalin-free tissue fixation for RNA and microRNA studies.

FineFix, RCL-2 and HOPE, three formalin-free fixatives, were compared to the common used formalin fixed tissue samples of lung cancer and were evaluated for their effects on quality, quantity and integrity of RNA and microRNA. Two commercially available RNA extraction Kits (RNeasy FFPE by Qiagen and RecoverAll™ Nucleic Acid Isolation by Ambion) were tested and optimized in order to determine an extraction protocol for RNA as well as miRNA independent of the fixative. Two selected miRNAs were quantified via TaqMan MicroRNA assays.

Positioning of necrotic lobular intraepithelial neoplasias (LIN, grade 3) within the sequence of breast carcinoma progression.

Lobular intraepithelial neoplasia Grade 3 (LIN3) is a recently recognized variant of intraepithelial lobular neoplasia (LIN) of the breast composed of either uniform, generally small cells with massive lobular distension, pleomorphic cells, signet-ring cells, or any cell type with necrosis. In contrast to classic forms of LIN, there is no consensus on therapeutic strategies for LIN3. In part this is due to the paucity of molecular data that could assist in defining the relationship of LIN3 to classic LIN and carcinomas.

The VEGF-system in primary pulmonary angiosarcomas and haemangioendotheliomas: new potential therapeutic targets?

Malignant epitheloid vascular tumors (epitheloid haemangioendotheliomas and angiosarcomas) of the lung are very rare lesions often posing difficulties in diagnosis. Due to their rare incidence no standardized therapy regimen is established. Surgical resection of the tumor is the mainstay of treatment, but in many cases, especially due to the multifocality of the tumor, negative resection margins cannot be achieved.

Prognostic significance of p16/cdkn2a loss in pleural malignant mesotheliomas.

Homozygous deletion of p16/CDKN2A is the most common genetic abnormality in malignant mesotheliomas. The aim of this study was to determine prognostic significance of p16/CDKN2A loss in malignant pleural mesotheliomas (MPM) as defined by immunohistochemistry and fluorescence in situ hybridization (FISH). High-density tissue microarrays were constructed from archival formalin-fixed paraffin-embedded samples of 48 MPM.

Sarcomatoid carcinomas of the lung--are these histogenetically heterogeneous tumors?

Sarcomatoid carcinomas (SC) of the lung are a heterogeneous group of nonsmall cell lung carcinomas (NSCLC) containing a sarcoma or sarcoma-like component. SC may represent an epithelial neoplasm undergoing divergent tissue differentiation originating from a single clone. Epithelial-mesenchymal transition (EMT) best describes the origin of the spindle and giant cells.

Chromosomal alterations in low-grade endometrial stromal sarcoma and undifferentiated endometrial sarcoma as detected by comparative genomic hybridization.

Objective: Endometrial stromal sarcomas (ESS) are very rare neoplasms constituting less than 0.5% of all malignant uterine tumors. The aim of the present study was to characterize the karyotypic abnormalities in these malignant mesenchymal tumors and to find specific chromosomal aberrations with eventual correlation with histologic grades.

Analysis of chromosome-11 aberrations in pulmonary and gastrointestinal carcinoids: an array comparative genomic hybridization-based study.

Carcinoid tumors are a heterogeneous group of neoplasms arising from the diffuse neuroendocrine system. Pulmonary as well as gastrointestinal carcinoids can be separated into those with low malignant and intermediate malignant potential. DNA losses of chromosome arm 11q are commonly seen in pulmonary neuroendocrine tumors.

Protein expression profiles in adenocarcinomas and squamous cell carcinomas of the lung generated using tissue microarrays.

With the appearance of defect-targeted therapies, the definition of tumour protein expression profiles has gained increasing importance. Two lung carcinoma tissue microarrays, one including 75 primary adenocarcinomas (ACs) and the other comprising 67 primary squamous cell carcinomas (SQCCs), were generated in the present study. On both arrays, each tumour was represented by an average of five cores.

Atypical goblet cell hyperplasia in congenital cystic adenomatoid malformation as a possible preneoplasia for pulmonary adenocarcinoma in childhood: A genetic analysis.

Congenital cystic adenomatoid malformation (CCAM) of the lung is a congenital lesion that is sometimes complicated by bronchioloalveolar adenocarcinoma (BAC). In some cases foci of atypical goblet cell hyperplasia (AGCH) can be found within the cysts. It has been proposed that CCAM and AGCH predispose to the development of BAC.

Bronchiolar columnar cell dysplasia--genetic analysis of a novel preneoplastic lesion of peripheral lung.

Atypical adenomatous hyperplasia is the only known precursor lesion of lung adenocarcinomas (ACs) so far. Here, we describe a new dysplastic lesion in the bronchioles of peripheral lung for which we propose the name bronchiolar columnar cell dysplasia (BCCD). Eight of fourteen BCCDs were successfully analyzed by means of comparative genomic hybridization (CGH).