Editorial

Special Focus on Investigative Techniques

This issue of Veterinary Pathology presents a series of articles on investigative techniques used by pathologists in different settings. For many years, hematoxylin and eosin (HE) and other histochemical stains were the main and typically the sole methodology to evaluate disease processes. Electron microscopy (EM), although used sporadically, contributed to the identification of pathogens and the study of disease processes. In the early 1970s, immunohistochemistry (IHC) started to play a role in the identification of pathogens, cell components, and neoplasia. The next significant leap in our ability to understand diseases came with the use of genomics to decipher changes in nucleic acids. These technological advances resulted in the identification of new diseases, reclassification of pathogens, and increased understanding of neoplasia and other entities in human beings and, to a lesser extent, in animals. Nextgeneration sequencing has a tremendous potential to elucidate the disease process and is currently used in many human and some animal diseases. As mentioned by medical pathologists,1,3,5,11 the field of pathology has been slow in ‘‘catching up’’ with the current trend. One problem is that, in many training institutions, pathology residents are still trained mostly in routine diagnostics rather than new technologies. For lack of experience, the pathologist may hesitate to interpret the results generated by these technologies or simply leave the interpretation to molecular biologists. Disease research (and eventually prognostication and theranostics) will require pathologists with expertise in both histopathology and genomic and molecular techniques.1,4 This expertise demands an understanding of the fundamentals of the methods as well as their applications and limitations. We hope this series of articles, albeit incomplete, raises awareness of the need for a ‘‘new pathologist.’’ Classic (routine) techniques such as histopathology with HE stain cannot be replaced by the new technologies. Histopathology remains a pillar of pathology; the article on factors affecting the visibility of a target tissue in histologic sections addresses this.10 A review article on ultrastructural methodologies follows. Electron microscopy, although considered ‘‘defunct’’ by some after the advent of IHC and other technologies, has a niche in the study of disease. The main problem, as the authors2 of this article acknowledge, is the progressive reduction of experts in electron microscopy. This article should challenge pathologists to adapt and advance EM techniques. One need only glance at the table of contents in current pathology journal issues to appreciate the importance of IHC in the study of human and animal disease. Several articles in this special issue reinforce this and describe the challenges of IHC in

Veterinary Pathology 2014, Vol 51(1) 5-6 ª The Author(s) 2013 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0300985813514949 vet.sagepub.com

terms of standardization and interpretation of results.12,13,16 Additional articles on IHC in this issue support its use, not only for diagnostics but also for prognostication and theranostics. The digital era has not only exponentially expanded the generation and evaluation of data but also reduced the bias of pathologists in the interpretation of results. Sophisticated software allows simultaneous evaluation of multiple IHC markers and multifaceted quantification of pathological changes. Several articles in this issue are focused on imaging or technologies that rely on image processing for interpretation.9,17,18 Genomic analysis has an extraordinary impact in human pathology and some animal diseases. The review article on nucleic acid–based methodologies in formalin-fixed tissues8 and another on laser capture microdissection7 emphasize the importance of these techniques and demonstrate how the humble paraffin block can be a tremendous source of information despite its shortcomings. The last group of articles in this issue of Veterinary Pathology is focused on the use of these new technologies, in combination with classic ones, in drug development14,15 and how the quality of results depends on the integrity of the sample.6 Publication of this project was made possible, in part, by the remarkable dedication of Veterinary Pathology editorial staff, from the managing editor to the photo editors. Last, but not least, we acknowledge the hard work of peer reviewers. Although these articles were written by experts, the constructive critiques of the reviewers definitely improved each manuscript. We sincerely appreciate the reviewers’ selfless contributions. J. A. Ramos-Vara Department of Comparative Pathobiology, Purdue University, West Lafayette, IN, USA J. D. Webster Department of Pathology, Genentech, Inc, San Francisco, CA, USA Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.

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References 1. Berman DM, Bosenberg MW, Orwant RL, et al. Investigative pathology: leading the post-genomic revolution. Lab Invest. 2012;92:4–8. 2. Cheville N, Stasko J. Techniques in electron microscopy of animal tissue. Vet Pathol. 2014;51:28–41. 3. Dry S, Grody WW, Papagni P. Stuck between a scalpel and a rock, or molecular pathology and legal-ethical issues in use of tissues for clinical care and research. Am J Clin Pathol. 2012; 137:346–355. 4. Haspel RL, Arnaout R, Briere L, et al. A curriculum in genomics and personalized medicine for pathology residents. Am J Clin Pathol. 2010;133:1–3. 5. Hess JL. What are anyway? The role of pathologists in the 21st century. Arch Pathol Lab Med. 2010;134:1424–1425. 6. Hostetter G, Varlan P, Edewaard E, et al. Veterinary and human biobanking practices: enhancing molecular simple integrity. Vet Pathol. 2014;51:270–280. 7. Liu H, McDowell CL, Hanson NE, et al. Laser capture microdissection for the investigative pathologist. Vet Pathol. 2014;51: 257–269. 8. Maes R, Ingeborg I, Wise A, et al. Beyond H&E: integration of nucleic acid–based analyses into diagnostic pathology. Vet Pathol. 2014;51:238–256. 9. Mansfield JR. Multispectral imaging: a review of its technical aspects and applications in anatomic pathology. Vet Pathol. 2014;51:185–210.

10. McGavin M. Factors affecting visibility of a target tissue in histologic sections. Vet Pathol. 2014;51:9–27. 11. Musser JM. Third-track pathology. Arch Pathol Lab Med. 2011; 135:687–688. 12. Pen˜a L, Adelina G, Goldschmidt M, et al. Canine mammary tumors: a review and consensus of standard guidelines on epithelial and myoepithelial phenotype markers, HER-2 and hormone receptor assessment using immunohistochemistry. Vet Pathol. 2014;51:127–145. 13. Ramos-Vara JA, Miller M. When tissue antigens and antibodies get along: revisiting the technical aspects of immunohistochemistry, the red, brown, and blue technique. Vet Pathol. 2014;51: 42–87. 14. Sasseville VG, Mansfield KG, Brees DJ. Safety biomarkers in preclinical development: translational potential. Vet Pathol. 2014;51:281–291. 15. Shinde V, Burke KE, Chakravarty A, et al. Applications of pathology-assisted image analysis of IHC-based biomarkers in oncology. Vet Pathol. 2014;51:292–303. 16. Ward JM, Rehg JE. Rodent immunohistochemistry: pitfalls and troubleshooting. Vet Pathol. 2014;51:88–101. 17. Webster JD, Dunstan RW. Whole-slide imaging and automated image analysis: considerations and opportunities in the practice of pathology. Vet Pathol. 2014;51:211–223. 18. Wood BR, Kiupel M, McNaughton D. Progress in Fourier transform infrared spectroscopic imaging applied to venereal cancer diagnosis. Vet Pathol. 2014;51:224–237.

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Special focus on investigative techniques.

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