Human Pathology (2007) 38, 11031104

www.elsevier.com/locate/humpath

Editorial

In situ techniques in diagnostic pathology

Many rapid advances are being made in understanding the molecular pathogenesis of tumors and infectious diseases. This knowledge is being used in diagnostic pathology as well as in making decisions about targeted therapies for specific diseases. Many new techniques such as RNA profiling, genomics, proteomics, and laser capture microdissection have contributed to these rapid advances [1-4]. For anatomic pathologists, the ability to visualize these changes in protein and nucleic acid levels in tissues under the microscope extend their ability to make pathologic diagnosis at the molecular level. In situ techniques have usually combined histopathologic analyses with innovations in chemistry and biochemistry over many decades. In the past 2 decades, advances in molecular biology have been joined to histological methods leading to the application of immunohistochemical and in situ hybridization techniques for tissue diagnoses. With the combination of these methods, the pathologist can readily observe changes in abnormal tissue and compare them with normal tissue in the same section under the microscope. These approaches have resulted in greater insights into the development and progression of disease processes than could be appreciated by morphologists in the past. One obvious advantage of this approach is that the trained morphologist does not have to assume which cell type in the tissues is contributing to the amplified or abnormal signal that is detected. Although some indirect techniques such as laser capture microdissection have also tried to bridge the gap between measuring molecular events and attributing these changes to a particular cell type, laser capture microdissection is at best an indirect approach, hence not as powerful as direct in situ observations. Four articles in this special section of this issue combine molecular techniques such as fluorescent (FISH) and chromogenic in situ hybridization (CISH) and in situ polymerase reaction with direct histopathologic observations using molecular techniques that have direct clinical diagnostic applications. The article by Lambros et al [5] examines CISH and FISH in breast cancer, the most widely used clinical application of these techniques. These authors show how in situ molecular genetic analyses are changing diagnostic and prognostic
0046-8177/$ see front matter 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.humpath.2007.05.005

approaches to breast cancer in the analysis of HER2 amplification, 12p13 amplification, and analysis of the basal-like phenotype in breast cancer. These studies illustrate how FISH and CISH are helping to unravel the complexity of breast cancer molecular genetics. The review by Nuovo [6] illustrates how routine histopathology is often insufficient in diagnosing the specific etiologic agents of infections. These studies show how in situ polymerase chain reaction amplification is required to localize some viruses in intact cells. These studies also illustrate the flexibility of in situ approaches for the detection of human papilloma virus in lesions such as cervical squamous intraepithelial lesions and cervical cancer. The in situ detection of Epstein Barr virus in a wide variety of pathological states, including posttransplant lymphoproliferative disorders and AIDS lymphoma, is illustrated. Similarly, localization of HIV in various tissues has provided new insights into the role of this virus in infection. The article by Halling and Kipp [7] illustrates how diagnostic cytology has rapidly progressed from observation of single cells or cell clusters to diagnosing some malignancies with molecular tools. These principles are illustrated in carcinomas of the bladder, biliary tract, and lung as well as dysplastic changes in Barrett esophagus and in esophageal carcinoma. The article by Powell et al [8] on metallographic methods represents another major step forward for in situ diagnostics because of the extreme sensitivity and resolution for visualizing endogenous gene copies in nonamplified tissues and for resolving multiple gene copies to allow copy enumeration in amplified tissues without the use of fluorescence optics. After reading these excellent articles, it is hoped that the reader will agree that the golden age of in situ diagnostics is rapidly approaching and that we can all be optimistic about the future of in situ techniques in diagnostic pathology. Ricardo V. Lloyd MD, PhD Department of Laboratory Medicine and Pathology Mayo Clinic Rochester, MN 55905, USA

1104

Editorial
[4] Jain KK. Role of oncoproteomics in the personalized management of cancer. Expert Rev Proteomics 2004;1:49-55. [5] Lambros MB, Natrajan R, Reis-Filho JS. Chromogenic and fluorescent in situ hybridization in breast cancer. HUM PATHOL 2007;38:1105-22. [6] Nuovo GJ. The utility of in situ based methodologies including in situ PCR for the diagnosis and study of viral infections. HUM PATHOL 2007;38:1123-36. [7] Halling KC, Kipp BR. Fluorescence in situ hybridization in diagnostic cytology. HUM PATHOL 2007;38:1137-44. [8] Powell RD, Pettay JD, Powell WF, et al. Metallographic in situ hybridization. HUM PATHOL 2007;38:1145-59.

References
[1] Cardoso J, Molenaar L, de Menezes FX, et al. Genomic profiling by DNA amplification of laser capture microdissected tissues and array CGH. Nucleic Acids Res 2004;32:e146. [2] Posadas EM, Simpkins F, Liotta LA, MacDonald C, Kohn EC. Proteomic analysis for the early detection and rational treatment of cancer-realistic hope? Ann Oncol 2005;16:16-22. [3] Espina V, Geho D, Mehta AI, Petricoin III EF, Liotta LA, Resenblatt KP. Pathology of the future: molecular profiling for targeted therapy. Cancer Invest 2005;23:36-46.