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Histopathology meets molecular pathology

2001; Elsevier BV; Volume: 92; Issue: 6 Linguagem: Inglês

10.1067/moe.2001.120519

1528-395X

Joseph A. Regezi,

dental development and anomalies

The accompanying review article, “Advanced diagnostic methods in oral and maxillofacial pathology. Part I: Molecular methods” (see this issue, pages 650-669), and its companion article, “Advanced diagnostic methods in oral and maxillofacial pathology. Part II: Immunohistochemical and immunofluorescent methods” (to be published in the January 2002 issue of this Journal) are intended to show what I believe represent state-of-the-art diagnostics as they apply to oral and maxillofacial pathology. These topics are of further importance because they now represent a rapidly growing facet of the oral literature. The application of molecular methods to tissue microscopy has the capacity to enhance our diagnostic abilities and our understanding of the underlying mechanisms of oral diseases that affect our patients. The advances in molecular technology will have a significant impact on all dental specialties. The purpose of this editorial is to give my view of what I believe are complementary roles that histopathology and molecular pathology play in the present and future practice of surgical oral and maxillofacial pathology. As an oral pathologist who has practiced surgical pathology for more years than I like to remember (more than 30 years), I have the advantage of age to help me formulate my perspective of the field. Please forgive me for some philosophical digression here, but having received my formal education in oral pathology in the late 1960s and early 1970s, I was ill-prepared for the molecular revolution that we have experienced in the past decade. My research training, such as it was, quickly became irrelevant. I'm sure that many of my colleagues would agree that it is a constant struggle to keep up with advancements in the field. It is, nonetheless, important to appreciate the power of molecular methodologies and to be willing to assess applications as they become available. It is incumbent on us to read and think about how new technologies and methods might potentially be used to solve some of the diagnostic dilemmas that we frequently face. Techniques in this rapidly expanding field, such as gene expression profiling,1Ladanyi M Chan WC Triche TJ Gerald WL. Expression profiling of human tumors: the end of surgical pathology?.J Mol Diagn. 2001; 3: 92-97Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar have the ability to help us decipher previously unanswerable questions about tumor biology. They may also offer alternative classification of diseases on the basis of molecular profiles and may—one day—better predict patient outcome from biopsy material. I was trained by several experienced mentors who were leaders in histopathologic diagnosis. Not surprisingly, what I learned from them continues to be the foundation of the majority of work that I do today: the histopathologic interpretation of routinely stained tissue sections. I believe that new molecular methodologies have added to and will continue to complement the sophistication of tissue diagnosis and prognostication. However, I also believe that they will not—at least not for many years to come—replace the histologic component of surgical pathology. Histopathology remains at the core of disease diagnosis. Tissue confirmation of diseases assessed this way continues to be the norm and is the “gold standard” with which all other methods are compared. That the dental and medical professions depend on microscopic diagnosis of diseases for direction in the management of patients attests to the continued relevance and reliability of histopathology.2Rushing L Joste N The surgical pathology report: standardizing the “gold standard.”.J Surg Oncol. 1997; 65: 1-2Crossref PubMed Scopus (8) Google Scholar Archived paraffin-embedded tissue has now become an incredibly valuable resource for molecular studies. For example, polymerase chain reaction amplification of DNA, and more recently RNA, extracted from tissue sections can be used to identify genetic alterations that are intimately associated with many oral diseases. Because the surgical pathologist is the guardian and gatekeeper of this archive, organization (diagnosis, demographics) and the willingness to make this material available to collaborating investigators can be important in the advancement of knowledge. Don't ask me to run a gel electrophoresis or extract DNA from a specimen and amplify it by polymerase chain reaction. This should be left up to those individuals with training and experience in molecular methods. Rather, ask me “How can one apply these molecular methods to the study of oral diseases?” Ask me “Can you explain in molecular terms the events leading to the static picture one sees under the microscope?” The surgical pathologist has an experienced and important perspective of clinical microscopic correlation—a perspective that the molecular scientist may not fully appreciate. Working together, molecular tools can be applied to practical problems to better understand disease mechanisms and improve diagnostic skills, ultimately aiding in the development of rational therapeutic regimens. We who are working in academic institutions are expected to be at the forefront of knowledge in our respective disciplines. With this comes the obligation to read continually and assess the current literature. Thus, we are in a unique position to ask pertinent questions about and to investigate oral diseases. Publishing the results of our studies, be they clinically or laboratory based, is a requisite of the positions we hold. Oral cancer is an important area within the domain of dentistry and is most likely to see the greatest impact of molecular technology initially. Already there is the promise of beneficial effects from molecular application. Mechanisms explaining the loss of cell cycle control and cell invasion are being described. The immunohistochemical and molecular methods used to decipher oral cancer pathogenesis are now moving into the diagnostic field. Translational studies leading to the identification of diagnostic and predictive tumor markers likely will be forthcoming in this decade and will have relevance to tumor diagnosis. The identification of tumor markers may eventually become a part of routine histologic reporting. In malignancies at other sites—for example, breast cancer— molecular methods have already shown that amplification of the HER2 /neu gene, leading to protein overexpression, gives some breast cancers a proliferation advantage. This knowledge has led to the development of an immunohistochemical staining method that allows the surgical pathologist to assess HER2 /neu gene protein product that has predictive value for individual breast cancer patients. Rather that diminishing, this type of practical application enhances the role and importance of histopathology and illustrates the need to better understand the molecular biology of a disease and how these genetic changes can be assessed in patient biopsy material. I would like to conclude with an appreciative note to Editor Alan Gould and his editorial board for their invitation to write these 2 articles—and for their critical appraisal. We believe that the subjects discussed have much practical value and are worthy of review; we hope that the readers of this Journal agree. Finally, we are well aware that many of our colleagues could have produced similar manuscripts, so we feel honored to have been asked.