Molecular Signatures of Lung and Pleural Tumors: Joint Symposium of the European Working Groups for Molecular Pathology and Pulmonary Pathology, 21st European Congress of Pathology

Archives of Pathology & Laboratory Medicine, Oct 2008 by Popper, Helmut H

The intent of this special section on Molecular Signatures of Lung and Pleural Tumors is to describe new methodologic developments in molecular pathology to the general pathologist as well as to the specialist. Pathology in general and pulmonary pathology in particular have made dramatic steps forward in recent decades: In the mid 1980s, the advent of immunohistochemistry revolutionized our research and diagnostic work. Polymerase chain reaction and in situ hybridization for selected mRNAs followed in the early 1990s. Analysis of DNA by chromosomal hybridization and cDNA array were the next steps in this story of success, but these new techniques showed how contamination of tumor tissues with normal tissues or with necrotic tissues could confuse test results. For example, analysis of gene expression of tumor tissues contaminated with normal tissues disclosed overexpression of genes usually found in normal lung, such as surfactant genes. This explains why results of some earlier investigations have not been reproducible.

In the 21st century, proteomics is the new player in this field. Proteins cannot only be extracted from fresh but also from formalin-fixed, paraffin-embedded tissue. These proteins can be quantitated, specific proteins can be evaluated, phosphorylation status can be assessed, protein arrays can be used to evaluate the expression pattern in a given tumor, and antibody arrays can be used to evaluate different proteins simultaneously. We now have the opportunity to combine these various methods to obtain the maximum amount of information from tumor tissues.

Today, genomic alterations can be explored using oligoarrays with a resolution of less than 100 base pairs, methylation status can be uncovered, the expression profile of mRNAs can be evaluated, the regulatory network of microRNAs can be integrated into the evaluation, and finally, the translation into proteins and the phosphorylation status of the proteins can be assessed. Therefore, the tools are there for functional genomics and proteomics, and the development of molecular target therapy.

Today, it is increasingly important for pathologists to have some knowledge of molecular pathology and molecular diagnostics.

Although other medical disciplines are entering the molecular field, only pathologists have the expertise to interpret the morphologic features of a disease and identify the tissue samples of interest for studies of molecular targeted therapy.

This special section was put together with the aim to update our readers on the new methodology and its application to pulmonary and pleural neoplasms. It is based on presentations held at the European Pathology Society Congress in Istanbul, Turkey, at a joint venture symposium on molecular pathology of lung cancer (the European Working Group for Pulmonary Pathology and the European Working Group for Molecular Pathology, September 2007). The topics were selected to cover genomic research, RNA expression analysis, proteomics, and aspects of their application for tumor pathology.

Helmut H. Popper, MD

Accepted for publication June 17, 2008.

From the Institute of Pathology, Medical University of Graz, Graz, Austria.

The author has no relevant financial interest in the products or companies described in this article.

Reprints: Helmut H. Popper, MD, Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, Graz, Styria A-8036, Austria (e-mail: helmut.popper@meduni-graz.at).

Helmut H. Popper holds a professorship at the Medical University of Graz. He serves as a staff member at the Institute of Pathology, doing surgical pathology and cytopathology. His primary interests are pulmonary, pleural, and mediastinal pathology. He is Director of the Laboratories for Molecular Cytogenetics, Environmental and Respiratory Pathology. Dr Popper received his MD at the Medical University of Graz (formerly Karl-Franzens-University). After initial studies in Pharmacology in Graz, Dr Popper did his residency and fellowship in pathology at the Institute of Pathology with subsequent additional training at the Armed Forces Institute of Pathology (Department of Pulmonary & Mediastinal Pathology), the Departments of Pathology at Stanford University, United States, and Papworth Hospital, United Kingdom (heart and lung transplantation pathology), and the Lovelace Inhalation Toxicology Research Institute, Albuquerque, NM (Inhalation Toxicology). He has authored more than 150 publications on pulmonary and pleural pathology, inhalation toxicology, as well as molecular and genetic pathology. Dr Popper is an associate editor in atomic pathology for the Archives of Pathology & Laboratory Medicine.