SOX9 has distinct roles in the formation and progression of different non-small cell lung cancer histotypes.

The transcription factor SOX9 is a key regulator of multiple developmental processes and is frequently re-expressed in non-small cell lung cancer (NSCLC). Its precise role in the progression of NSCLC histotypes has, however, remained elusive. We show that SOX9 expression relates to poor overall survival and invasive histopathology in human non-mucinous adenocarcinoma and is absent in murine early minimally invasive and low in human in situ adenocarcinoma.

Performance of Finnish biobanks in nationwide pulmonary carcinoid tumour research.

Finnish hospital-integrated biobanks administer millions of formalin-fixed paraffin-embedded tissue samples collected within the clinical diagnostics. According to the Finnish Biobank Act, these samples can be coupled with patients' clinical follow-up data and the data retrieved from national health registries. We collected a nationwide pulmonary carcinoid tumour series from Finnish biobanks to study prognostic factors as well as to explore how the number of tumours found in the Finnish biobanks corresponds to the number of tumours registered by the Finnish Cancer Registry (FCR).

Receptor Tyrosine Kinase Signaling Networks Define Sensitivity to ERBB Inhibition and Stratify -Mutant Lung Cancers.

Most non-small cell lung cancers (NSCLC) contain nontargetable mutations, including , or alterations. By coupling drug sensitivity profiling with drug response studies, we aimed to identify drug vulnerabilities for these NSCLC subtypes. Primary adenosquamous carcinoma (ASC) or adenocarcinoma (AC) cultures were established from (KL) tumors or AC cultures from (KP) tumors.

PD-1 and PD-L1 expression in pulmonary carcinoid tumors and their association to tumor spread.

Pulmonary carcinoid (PC) tumors are rare tumors that account for approximately 1% of all lung cancers. The primary treatment option is surgery, while there is no standard treatment for metastatic disease. As the number of PCs diagnosed yearly is increasing, there is a need to establish novel therapeutic options.

CDKN2A copy number and p16 expression in malignant pleural mesothelioma in relation to asbestos exposure.

Background: Deletion of the CDKN2A locus is centrally involved in the development of several malignancies. In malignant pleural mesothelioma (MPM), it is one of the most frequently reported genomic alteration. MPM is strongly associated with a patients' asbestos exposure.

Somatostatin Receptor Expression Is Associated With Metastasis and Patient Outcome in Pulmonary Carcinoid Tumors.

Context: Pulmonary carcinoids (PCs) belong to neuroendocrine tumors that often overexpress somatostatin receptors (SSTRs). This overexpression provides a molecular basis for tumor imaging and treatment with somatostatin analogs.

Objective: To evaluate SSTR1 to SSTR5 distribution in a large set of PC tumors and to investigate whether the expression is associated with clinicopathological and outcome data.

Clinicopathological indicators of survival among patients with pulmonary carcinoid tumor.

Background: Pulmonary carcinoids (PC) are rare malignant neoplasms that cover approximately 1% of all lung cancers. PCs are classified by histological criteria as either typical (TC) or atypical (AC). Histological subtype is the most studied prognostic factor.

Spatial aspects of oncogenic signalling determine the response to combination therapy in slice explants from Kras-driven lung tumours.

A key question in precision medicine is how functional heterogeneity in solid tumours informs therapeutic sensitivity. We demonstrate that spatial characteristics of oncogenic signalling and therapy response can be modelled in precision-cut slices from Kras-driven non-small-cell lung cancer with varying histopathologies. Unexpectedly, profiling of in situ tumours demonstrated that signalling stratifies mostly according to histopathology, showing enhanced AKT and SRC activity in adenosquamous carcinoma, and mitogen-activated protein kinase (MAPK) activity in adenocarcinoma.

Analysis of the Histologic Features Associated With Interobserver Variation in Idiopathic Pulmonary Fibrosis.

The histologic manifestation of idiopathic pulmonary fibrosis (IPF) is usual interstitial pneumonia (UIP), which is a good prognostic determinant of survival compared with other histologic interstitial lung disease patterns. According to the current international guidelines, the histologic features of suspected IPF/UIP are divided into 4 categories: UIP, probable UIP, possible UIP, and not UIP pattern. Four pulmonary pathologists who were blinded to clinicoradiologic information reevaluated 50 surgical lung biopsies (83.

Asbestos-associated genome-wide DNA methylation changes in lung cancer.

Previous studies have revealed a robust association between exposure to asbestos and human lung cancer. Accumulating evidence has highlighted the role of epigenome deregulation in the mechanism of carcinogen-induced malignancies. We examined the impact of asbestos on DNA methylation.

Cell of Origin Links Histotype Spectrum to Immune Microenvironment Diversity in Non-small-Cell Lung Cancer Driven by Mutant Kras and Loss of Lkb1.

Lung cancers exhibit pronounced functional heterogeneity, confounding precision medicine. We studied how the cell of origin contributes to phenotypic heterogeneity following conditional expression of Kras and loss of Lkb1 (Kras;Lkb1). Using progenitor cell-type-restricted adenoviral Cre to target cells expressing surfactant protein C (SPC) or club cell antigen 10 (CC10), we show that Ad5-CC10-Cre-infected mice exhibit a shorter latency compared with Ad5-SPC-Cre cohorts.

Incidence, Risk Factors, and Outcome of Life-Threatening Ventricular Arrhythmias in Giant Cell Myocarditis.

Background: Ventricular tachyarrhythmias are characteristic of giant cell myocarditis, but their true incidence, predictors, and outcome are unknown.

Methods And Results: Our work involved 51 patients with giant cell myocarditis (35 women) aged 52±12 years. Their medical records were reviewed for history, results of laboratory and imaging studies, and occurrence of serious cardiac events, including life-threatening ventricular tachyarrhythmias.

Long-term outcome and its predictors in giant cell myocarditis.

Aims: There are no studies focusing on prognostic factors in giant cell myocarditis (GCM). We aimed to identify predictors of transplant-free survival in GCM.

Methods And Results: We analysed the details of 46 patients with GCM (31 women, mean age 51 ± 12 years) seen at our hospital since 1991 and followed for the occurrence of cardiac death or transplantation till May 2015.

[Molecular pathologic diagnosis of lung cancer requires basic knowledge also from clinicians].

Besides histological classification of lung cancers, molecular biological examination of tumors is part of modern diagnostics of lung cancers, and cancer therapies are based on molecular biological diagnosis. Current laboratory technique enables the examination of many mutations as part of standard routine diagnosis, necessitating functional multidisciplinary collaboration, with the pathologist playing a central role in the handling of the specimens. In the future, especially pathologists, pulmonary specialists and oncologists are expected to need a good command of molecular biological data on lung cancer, but basic knowledge will be required also from other physicians working with lung cancer patients.

[Diagnostics of non-small cell lung carcinoma].

ALK inhibitor therapy is individual cancer treatment, in which the targeted drug therapy is directed to a patient group that is likely to benefit from the therapy. The detection in the tumor of ALK gene (anaplastic lymphoma kinase) rearrangement is a prerequisite for the ALK inhibitor therapy for non-small cell lung carcinoma. The ALK assay should be performed for non-squamous cellular non-small cell lung carcinomas, especially adenocarcinomas.

Targeted resequencing reveals ALK fusions in non-small cell lung carcinomas detected by FISH, immunohistochemistry, and real-time RT-PCR: a comparison of four methods.

Anaplastic lymphoma receptor tyrosine kinase (ALK) gene rearrangements occur in a subgroup of non-small cell lung carcinomas (NSCLCs). The identification of these rearrangements is important for guiding treatment decisions. The aim of our study was to screen ALK gene fusions in NSCLCs and to compare the results detected by targeted resequencing with results detected by commonly used methods, including fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), and real-time reverse transcription-PCR (RT-PCR).

Comparison of targeted next-generation sequencing (NGS) and real-time PCR in the detection of EGFR, KRAS, and BRAF mutations on formalin-fixed, paraffin-embedded tumor material of non-small cell lung carcinoma-superiority of NGS.

The development of tyrosine kinase inhibitor treatments has made it important to test cancer patients for clinically significant gene mutations that influence the benefit of treatment. Targeted next-generation sequencing (NGS) provides a promising method for diagnostic purposes by enabling the simultaneous detection of multiple mutations in various genes in a single test. The aim of our study was to screen EGFR, KRAS, and BRAF mutations by targeted NGS and commonly used real-time polymerase chain reaction (PCR) methods to evaluate the feasibility of targeted NGS for the detection of the mutations.

Diagnosis, treatment, and outcome of giant-cell myocarditis in the era of combined immunosuppression.

Background: Giant-cell myocarditis often escapes diagnosis until autopsy or transplantation and has defied proper treatment trials for its rarity and deadly behavior. Current therapy rests on multiple-drug immunosuppression but its prognostic influence remains poorly known. We set out to analyze (1) our experience in diagnosing giant-cell myocarditis and (2) the outcome of patients on combined immunosuppression.

Carbonic anhydrase IX in malignant pleural mesotheliomas: a potential target for anti-cancer therapy.

Malignant mesothelioma is a neoplasm deriving from mesothelial cells, which line the body cavities. The most common type is malignant pleural mesothelioma (MPM), which is a locally aggressive malignancy with poor prognosis. To improve both the clinical diagnostics and treatment it is necessary to identify novel molecular targets which are characteristic for MPM.

Expression of snail, twist, and Zeb1 in malignant mesothelioma.

We examined 56 malignant mesotheliomas, 117 lung adenocarcinomas, and 34 metastatic lung adenocarcinomas with antibodies to transcription factors involved in epitheliomesenchymal transition. The tumors were stained immunohistochemically with antibodies zeb1, twist, and snail. Malignant mesotheliomas exhibited a stronger expression of zeb1 and twist than lung adenocarcinomas (p < 0.

Accumulation of genomic alterations in 2p16, 9q33.1 and 19p13 in lung tumours of asbestos-exposed patients.

We have previously demonstrated an association between genomic alterations in 19p13, 2p16, and 9q33.1 and asbestos exposure in patients' lung tumours. This study detected allelic imbalance (AI) in these regions in asbestos-exposed lung cancer (LC) patients' histologically normal pulmonary epithelium.

Regulation of TGF-β storage and activation in the human idiopathic pulmonary fibrosis lung.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease of unknown cause. The pathogenesis of the disease is characterized by fibroblast accumulation and excessive transforming growth factor-β (TGF-β) activation. Although TGF-β activation is a complex process involving various protein interactions, little is known of the specific routes of TGF-β storage and activation in human lung.

Outcome of patients with ductal carcinoma in situ and sentinel node biopsy.

Background: In sentinel node biopsy (SNB), tumor-positive findings, mainly micrometastases and isolated tumor cells (ITC) have been found in up to 8%-16% of patients with pure ductal carcinoma in situ (DCIS) or microinvasive DCIS (DCISM). The prognostic significance of such findings is largely unknown. The aim of this study is to examine the outcome of DCIS and DCISM patients with SNB.

Cysteine-rich protein 1 is regulated by transforming growth factor-β1 and expressed in lung fibrosis.

Transforming growth factor-β (TGF-β) is a diverse cytokine regulating growth, apoptosis, differentiation, adhesion, invasion, and extracellular matrix production. Dysregulation of TGF-β is associated with fibrotic disorders and epithelial-mesenchymal transition, and has been linked with idiopathic pulmonary fibrosis (IPF). Cysteine-rich protein 1 (CRP1) is a small LIM-domain containing protein involved in smooth muscle differentiation.