DOG1 immunohistochemical staining of testicular biopsies is a reliable tool for objective assessment of infertility |
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| Institution: | 1. Department of Pathology, St. Elizabeth Healthcare, Edgewood, KY, USA;2. Department of Pathology & Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA;3. Department of Pathology, Brown University, Providence, RI, USA;1. Weill Cornell Medicine- New York Presbyterian Hospital, Department of Dermatopathology, 1300 York Avenue, New York, NY 10065, United States of America;2. Weill Cornell Medicine- New York Presbyterian Hospital, Hematology/Oncology, 1300 York Avenue, New York, NY 10065, United States of America;3. Department of Dermatology, Yale University School of Medicine, New Haven, CT, United States of America;4. Memorial Sloan Kettering Cancer Center, Section of Dermatopathology, 1275 York Avenue, New York, NY 10065, United States of America;5. Department of Dermatology, Donald and Barbara Zucker School of Medicine, At New Hyde Park, N.Y., United States of America;1. Harvard Medical School, Boston, MA, USA;2. Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA;3. Pathology Service, Massachusetts General Hospital, Boston, MA, USA;4. Center for Diversity and Inclusion, Massachusetts General Hospital, Boston, MA, USA;5. University of North Carolina, Chapel Hill, NC, USA;1. Department of Pathology, University of Pittsburgh Medical Center, A711 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, USA;2. Department of Radiology, University of Pittsburgh Medical Center, Presbyterian University Hospital Suite E204, 200 Lothrop Street, Pittsburgh, PA 15213, USA;3. Division of Hematopathology, University of Pittsburgh Medical Center, Hill Building, 3rd Floor, 3477 Euler Way, Pittsburgh, PA 15213, USA;1. The Ohio State University Comprehensive Cancer Center, Columbus, OH, United States of America;2. Phylogeny Medical Laboratory, Powell, OH, United States of America;3. National Institute of Infectious Diseases Evandro Chagas-Oswaldo Cruz Foundation (INI/FIOCRUZ), Rio de Janeiro, Brazil;4. Fiocruz National Institute of Women''s, Children and Adolescent''s Health Fernandes Figueira, Rio de Janeiro, Brazil;5. Cornell Medical Center, United States of America;1. Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA;2. At submission Dr. Hidalgo-Lopez was working in AMGEN, Thousand Oaks, CA, USA;1. Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA;2. School of Biological Sciences, National Institute of Science Education and Research, Bhubaneswar, India;3. Center for Diagnostic Pathology, AdventHealth, Florida Hospital, University of Central Florida, Orlando, FL, USA;4. Department of Gynecologic Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA;5. Department of Pediatrics, University of Massachusetts, Worcester, MA, USA |
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| Abstract: | Testicular biopsy may be a component of the work-up of male infertility. However, no reliable diagnostic tools are available for objective quantitative assessment of spermatogenic cells. It is well known that MAGE-A4 is selectively expressed in spermatogonia and our group has previously demonstrated that DOG1 differentially stains germ cells. Therefore, we performed DOG1 and a double stain cocktail (DOG1 and 57b murine monoclonal anti-MAGE-A4) immunohistochemical stains on 40 testicular infertility biopsies (10 each with active spermatogenesis, Sertoli cell-only, hypospermatogenesis, and maturation arrest), 25 benign seminiferous tubules from radical orchiectomies, and 5 spermatocytic tumors (ST). In biopsies/resections with active spermatogenesis, DOG1 stained spermatocytes and spermatids and was absent in spermatogonia, while MAGE-A4 stained spermatogonia and primary spermatocytes (weak). In hypospermatogenesis, DOG1 highlighted decreased spermatocytes/spermatids and MAGE-A4 highlighted decreased spermatogonia. DOG1 staining confirmed decreased to absent spermatocytes in maturation arrest and MAGE-A4 staining established the presence of preserved spermatogonia in all cases. All STs were negative for DOG1 and positive for MAGE-A4, while all Sertoli cell-only cases were negative for DOG1 and the double stain cocktail. In conclusion, we confirmed that DOG1 is expressed in spermatocytes and spermatids and MAGE-A4 highlights primarily spermatogonia. Usage of these stains facilitates confirmation of maturation arrest, assessment of the percentage of testis involvement in hypospermatogenesis and identification of mixed patterns. Finally, this study supports that the differentiation of STs is more closely related to spermatogonia than the more mature spermatocytes. |
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