Low tumour cell content in a lung tumour bank: implications for molecular characterisation.

Lung cancer encompasses multiple malignant epithelial tumour types, each with specific targetable, potentially actionable mutations, such that precision management mandates accurate tumour typing. Molecular characterisation studies require high tumour cell content and low necrosis content, yet lung cancers are frequently a heterogeneous mixture of tumour and stromal cells. We hypothesised that there may be systematic differences in tumour cell content according to histological subtype, and that this may have implications for tumour banks as a resource for comprehensive molecular characterisation studies in lung cancer.

Mitosis trumps T stage and proposed international association for the study of lung cancer/american thoracic society/european respiratory society classification for prognostic value in resected stage 1 lung adenocarcinoma.

Introduction: We investigated whether a group of pathologists could reproducibly apply the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification for lung adenocarcinoma to a cohort of stage 1 tumors and whether this architectural classification and/or other parameters could demonstrate survival advantage.

Methods: A total of 145 cases of 7 edition of tumor, node, metastasis stage 1 adenocarcinoma were retrospectively reviewed for predominant architectural pattern, including cribriform pattern, nuclear grade, mitotic index, and necrosis. The parameters were assessed for reproducibility and survival and using multivariate analysis, compared with stage, age, and sex.

MicroRNA-34c is associated with emphysema severity and modulates SERPINE1 expression.

Background: MicroRNAs (MiRNA) are small non-coding RNAs that regulate gene expression. The aim of this study was to identify miRNAs differentially expressed between mild and moderately emphysematous lung, as well as their functional target mRNAs. Resected lung from patients with COPD undergoing lung cancer surgery was profiled using miRNA (Agilent Human miRNA profiler G4470 V1.

The pivotal role of pathology in the management of lung cancer.

The last decade has seen significant advances in our understanding of lung cancer biology and management. Identification of key driver events in lung carcinogenesis has contributed to the development of targeted lung cancer therapies, heralding the era of personalised medicine for lung cancer. As a result, histological subtyping and molecular testing has become of paramount importance, placing increasing demands on often small diagnostic specimens.

Cystic lung disease.

This review addresses the pathology of lung disease in which the predominant finding is diffuse cystic change. Although cysts may be found radiologically in a wide variety of disease states, the entities discussed are those most likely to be encountered in biopsies where the underlying aetiology is unclear. These include Langerhans cell histiocytosis, lymphangioleiomyomatosis and Birt-Hogg-Dubé syndrome, and recent advances in the molecular pathology of these entities are reviewed.

Phenotypes and karyotypes of human malignant mesothelioma cell lines.

Background: Malignant mesothelioma is an aggressive tumour of serosal surfaces most commonly pleura. Characterised cell lines represent a valuable tool to study the biology of mesothelioma. The aim of this study was to develop and biologically characterise six malignant mesothelioma cell lines to evaluate their potential as models of human malignant mesothelioma.

Pleural fluid cell-free DNA integrity index to identify cytologically negative malignant pleural effusions including mesotheliomas.

Background: The diagnosis of malignant pleural effusions (MPE) is often clinically challenging, especially if the cytology is negative for malignancy. DNA integrity index has been reported to be a marker of malignancy. The aim of this study was to evaluate the utility of pleural fluid DNA integrity index in the diagnosis of MPE.

Whole genome sequencing for lung cancer.

Lung cancer is a leading cause of cancer related morbidity and mortality globally, and carries a dismal prognosis. Improved understanding of the biology of cancer is required to improve patient outcomes. Next-generation sequencing (NGS) is a powerful tool for whole genome characterisation, enabling comprehensive examination of somatic mutations that drive oncogenesis.

MS4A1 dysregulation in asbestos-related lung squamous cell carcinoma is due to CD20 stromal lymphocyte expression.

Asbestos-related lung cancer accounts for 4-12% of lung cancers worldwide. We have previously identified ADAM28 as a putative oncogene involved in asbestos-related lung adenocarcinoma (ARLC-AC). We hypothesised that similarly gene expression profiling of asbestos-related lung squamous cell carcinomas (ARLC-SCC) may identify candidate oncogenes for ARLC-SCC.

Array-comparative genomic hybridization reveals loss of SOCS6 is associated with poor prognosis in primary lung squamous cell carcinoma.

Background: Primary tumor recurrence commonly occurs after surgical resection of lung squamous cell carcinoma (SCC). Little is known about the genes driving SCC recurrence.

Methods: We used array comparative genomic hybridization (aCGH) to identify genes affected by copy number alterations that may be involved in SCC recurrence.

Mesothelial markers in high-grade breast carcinoma.

Aims: Advances in molecular profiling have subdivided breast carcinomas into distinct subtypes. Basal carcinomas are generally oestrogen receptor (ER)-progesterone receptor (PR)-/human epidermal growth factor receptor 2 (HER2)-, and cytokeratin (CK)5/6+. This profile overlaps with that of mesothelial cells.

Diagnostic molecular biomarkers for malignant pleural effusions.

Malignant pleural effusions (MPEs) are a common and important cause of cancer-related mortality and morbidity. Prompt diagnosis using minimally invasive tests is important because the median survival after diagnosis is only 4-9 months. Pleural fluid cytology is pivotal to current MPE diagnostic algorithms but has limited sensitivity (30-60%).

Genes and gene ontologies common to airflow obstruction and emphysema in the lungs of patients with COPD.

Chronic obstructive pulmonary disease (COPD) is a major public health problem with increasing prevalence worldwide. The primary aim of this study was to identify genes and gene ontologies associated with COPD severity. Gene expression profiling was performed on total RNA extracted from lung tissue of 18 former smokers with COPD.

Common pathogenic mechanisms and pathways in the development of COPD and lung cancer.

Introduction: Lung cancer and COPD commonly coexist in smokers, and the presence of COPD increases the risk of developing lung cancer. In addition to smoking cessation and preventing smoking initiation, understanding the shared mechanisms of these smoking-related lung diseases is critical, in order to develop new methods of prevention, diagnosis and treatment of lung cancer and COPD.

Areas Covered: This review discusses the common mechanisms for susceptibility to lung cancer and COPD, which in addition to cigarette smoke, may involve inflammation, epithelial-mesenchymal transition, abnormal repair, oxidative stress, and cell proliferation.

MicroRNA-218 is deleted and downregulated in lung squamous cell carcinoma.

MicroRNAs (miRNAs) are a family of small, non-coding RNA species functioning as negative regulators of multiple target genes including tumour suppressor genes and oncogenes. Many miRNA gene loci are located within cancer-associated genomic regions. To identify potential new amplified oncogenic and/or deleted tumour suppressing miRNAs in lung cancer, we inferred miRNA gene dosage from high dimensional arrayCGH data.

Symbolic rule-based classification of lung cancer stages from free-text pathology reports.

Objective: To classify automatically lung tumor-node-metastases (TNM) cancer stages from free-text pathology reports using symbolic rule-based classification.

Design: By exploiting report substructure and the symbolic manipulation of systematized nomenclature of medicine-clinical terms (SNOMED CT) concepts in reports, statements in free text can be evaluated for relevance against factors relating to the staging guidelines. Post-coordinated SNOMED CT expressions based on templates were defined and populated by concepts in reports, and tested for subsumption by staging factors.

ADAM28: a potential oncogene involved in asbestos-related lung adenocarcinomas.

Asbestos-related lung cancer accounts for 4-12% of all lung cancers worldwide. Since putative mechanisms of carcinogenesis differ between asbestos and tobacco induced lung cancers, tumors induced by the two agents may be genetically distinct. To identify gene expression biomarkers associated with asbestos-related lung tumorigenicity we performed gene expression array analysis on tumors of 36 patients with primary lung adenocarcinoma, comparing 12 patients with lung asbestos body counts above levels associated with urban dwelling (ARLC-AC: asbestos-related lung cancer-adenocarcinoma) with 24 patients with no asbestos bodies (NARLC-AC: non-asbestos related lung cancer-adenocarcinoma).

Lung asbestos content in lungs resected for primary lung cancer.

Introduction: The majority of Australia's burden of lung cancer occurs in current or former tobacco smokers. To determine the possible contribution of asbestos exposure in Australians presenting with primary lung cancer, we measured lung asbestos content in cases resected consecutively at a single cardio-thoracic hospital.

Methods: Asbestos bodies were quantified by lung tissue digestion, filtration, and light microscopy, and were correlated with exposure questionnaires and clinicopathological features.

Collection of cancer stage data by classifying free-text medical reports.

Cancer staging provides a basis for planning clinical management, but also allows for meaningful analysis of cancer outcomes and evaluation of cancer care services. Despite this, stage data in cancer registries is often incomplete, inaccurate, or simply not collected. This article describes a prototype software system (Cancer Stage Interpretation System, CSIS) that automatically extracts cancer staging information from medical reports.

Expression profiling defines a recurrence signature in lung squamous cell carcinoma.

Lung cancer remains the leading cause of cancer death worldwide. Overall 5-year survival is approximately 10-15% and despite curative intent surgery, treatment failure is primarily due to recurrent disease. Conventional prognostic markers are unable to determine which patients with completely resected disease within each stage group are likely to relapse.

Transient elevation of the tumor markers CA 15-3 and CASA as markers of interstitial lung disease rather than underlying malignancy in dermatomyositis sine myositis.

A 37-year-old woman with severe interstitial lung disease associated with dermatomyositis sine myositis is reported. A thoracoscopic lung biopsy revealed organizing diffuse alveolar damage. Significantly elevated serum levels of the tumor markers CA 15-3 and CASA (cancer-associated serum antigen) were detected, but no evidence of an underlying malignancy (including breast and ovarian) was found on serial clinical and radiologic examinations.

The role of left and right ventricular early diastolic Doppler tissue echocardiographic indices in the evaluation of acute rejection in orthotopic heart transplant.

Background: The aim was to evaluate whether Doppler tissue echocardiographic early diastolic indices of both the right and left ventricle (LV) may assist in the detection of acute heart transplant (HT) rejection.

Methods: In all, 44 consecutive patients with HT (mean age 52.0 +/- 9.

'Iron lung': distinctive bronchoscopic features of acute iron tablet aspiration.

Three confirmed cases of acute iron tablet-induced necrosis due to a fulminant chemical burn injury to the tracheobronchial tree as a result of accidental inhalation and/or aspiration of iron tablets are described. Although histological confirmation has been relied upon for diagnosis, the distinctive bronchoscopic features may allow prompt recognition and treatment by bronchoscopists to prevent this potentially fatal condition.