Page 94 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition
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CHAPTER 3  The Pathology of Neoplasia  73



            TABLE 3.7     Common Diagnostic Immunohistochemical Markers/Panels and Respective Tumor Types in Cats and
                       Dogs—cont’d
  VetBooks.ir  Tumor Type    Molecular Marker(s)  Localization/Expression  Comments                    References
                                       +/–
                                               Chromogranin = Cyto
                                                                 All are generic markers of NE origin. Recommended to
                             Chromogranin A
                                                                                                       138,174,203
             Neuroendocrine
               tumors        Synaptophysin +/–  Synaptophysin = Cyto  run in concert because NE tumors are often variably
                                +
                             NSE  [Hormone-specific   NSE = Cyto   immunoreactive. NSE is found in a number of cell
                               antibodies (e.g.,                   types and therefore NE specificity, but it is useful in
                               antiglucagon, insulin,              combination with other NE markers.
                               thyroglobulin and cal-
                               citonin (see Thyroid
                               Tumor, later), may
                               help determine spe-
                               cific histogenesis].
             Plasma cell tumor  MUM-1/IRF4 +   MUM-1 = N         In humans, plasma cell neoplasms, multiple myeloma,   204
                             CD18 +/−          CD18, CD3, CD79a = PM  and plasmablastic lymphomas are typically negative
                             CD3 −             Pax5 = N            for Pax5. Pax5 expression via IHC in similar canine
                             CD79a +/−  (Pax5 )                    tumors, has not been reported.
                                       −
             Rhabdomyoma,    Vimentin +        Vimentin, Desmin,    Desmin (see Leiomyoma, leiomyosarcoma). Myoglobin   206–208
               rhabdomyosarcoma  Desmin +        Myoglobin = Cyto  is typically a late-stage marker; may be negative in
                             Myoglobin +/−     MyoD1 and myogenin = N  poorly differentiated rhabdomyosarcomas.
                                −
                             SMA  (MyoD1 +/−                     Myo-D1 and myogenin can be useful in undifferentiated
                             Myogenin +/− ;                        tumors. (MyoD-1 and myogenin are not routinely
                               see comments)                       available).
                                                                 PTAH is a histochemical stain that may highlight cross
                                                                   striations of skeletal muscle.
                                   + e
             Sarcoma         Vimentin          Cyto                                                    174–176
                             Cytokeratin −
             Synovial cell sarcoma  Vimentin +  Vimentin, cytokeratin   Histogenesis is controversial. Relevance of cytokeratin   209,210
                             Cytokeratin +/–     = Cyto            expression has been questioned. May recruit large
                             CD18 –            CD18 = PM           numbers of CD18+ histiocytes, making distinction
                                                                   from articular/periarticular histiocytic sarcoma chal-
                                                                   lenging.
             Thyroid tumor: fol-  Thyroglobulin +  Thyroglobulin = Cyto  Thyroglobulin = provides iodination sites for the   205,211–213
               licular epithelial   TTF-1 +    TTF-1 = N           production of thyroid hormones, TTF-1 = nuclear
               origin (follicular   Calcitonin −  Calcitonin = Cyto  transcription factor specific to thyroid tissue save
               carcinoma; follicu-  Chromogranin A −               for pulmonary epithelium, calcitonin = polypeptide
               lar, solid, or mixed   Synaptophysin −              secreted by thyroid C-cells; counteracts effects of PTH
               subtypes)     NSE −                                 by reducing blood Ca 2+

             Thyroid tumor: C-cell   Thyroglobulin −  As above   As for Thyroid tumor: follicular epithelial origin  211–213
               /parafollicular cell   TTF-1 +
               origin (medullary   Calcitonin +
               C-cell carcinoma)  Chromogranin A +
                             Synaptophysin +
                             NSE +
             This table provides common diagnostic immunohistochemical markers used in veterinary oncologic pathology on formalin-fixed, paraffin-embedded tissue sections. Immunohistochemical stains should
             always be interpreted in conjunction with routine (hematoxylin & eosin) histopathologic evaluation and in the presence of appropriately stained positive and negative control tissues. Positive immunoreac-
             tivity supports histogenesis; however, negative immunoreactivity does not definitively rule out histogenesis because of the potential dedifferentiation of neoplastic cells with loss of antigen expression, in
             addition to the potential for technical error (false negative).
             Ab, antibody, BSAP, B-cell–specific activator protein; Cyto, cytoplasmic; DOG1, discovered on gastrointestinal tumor 1; EC, endothelial cell; EMT, epithelial-mesenchymal transition; Factor VIII-RAg/vWF,
             factor VIII–related antigen/von Willebrand factor; GFAP, glial fibrillary acidic protein; Gp, glycoprotein; IFP, intermediate filament protein; IHC, immunohistochemistry; MKs, megakaryocytes; MUM-1/IRF4,
             multiple myeloma 1/interferon regulatory factor 4; N, nuclear; NE, neuroendocrine; NSE, neuron-specific enolase; PECAM, platelet endothelial cell adhesion molecule; PM, plasma membrane; PTH,
             parathyroid hormone; PTAH, phosphotungstic acid-hematoxylin; RTK, tyrosine kinase receptor; SMA, smooth muscle actin; TEM, Transmission electron microscopy; TRP, tyrosinase-related protein; TTF-1,
             thyroid transcription factor-1; Vim, vimentin.
             a Generic marker for tumors of epithelial origin.
             b Iba1 may be helpful in differentiating histiocytic tumors from other round cell tumors. 187
             c KIT/CD117 is supportive of but should not be considered diagnostic for mast cell tumor because it is not mast-cell specific; it has been shown to carry prognostic relevance in canine cutaneous mast cell
             tumor based on its cellular localization/expression pattern determined by means of IHC. 116
             d Rare positivity in amelanotic melanomas.
             e Generic marker for tumors of mesenchymal cell origin.
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