Table 1:

Next-Generation Immunohistochemical Markers Discussed in This Review

Marker	Useful in Diagnosis of:	Next-Generation IHC “Qualifications”
PAX8	Müllerian, renal, and thyroid carcinoma; thymic neoplasms (with polyclonal antibody); pancreatic origin of well-differentiated neuroendocrine tumor (with polyclonal antibody)	Lineage-restricted transcription factor
MDM2/CDK4	Well- and dedifferentiated liposarcoma	Protein correlate of molecular genetic event
GATA-3	Breast and urothelial carcinoma; also expressed by pheochromocytoma/paraganglioma, choriocarcinoma, mesonephric carcinoma, parathyroid tumors, and pituitary gonadotroph and TSH-expressing tumors; often expressed by mesothelioma, chromophobe renal cell carcinoma, and cutaneous epithelial neoplasms; variably expressed by yolk sac tumor	Lineage-restricted transcription factor
ERG	Vascular neoplasms; also expressed by subsets of prostate cancer, Ewing sarcoma, and acute leukemia; antibodies to N-terminus label epithelioid sarcoma	Lineage-restricted transcription factor
Islet 1	Pancreatic origin of well-differentiated neuroendocrine tumor	Lineage-restricted transcription factor
PAX6	Pancreatic origin of well-differentiated neuroendocrine tumor	Lineage-restricted transcription factor
SALL4	Germ cell neoplasia; also expressed by hepatoid adenocarcinoma; may be frequently expressed by rhabdoid and Wilms tumor; aberrant expression in a significant minority (20-30%) of serous, gastric, urothelial, and biliary carcinomas	Lineage-restricted transcription factor
SOX10	Melanocytic, nerve sheath, and myoepithelial tumors; also often (60%) expressed by triple-negative breast cancer	Lineage-restricted transcription factor
INI1/SMARCB1 (loss)	Epithelioid sarcoma; malignant rhabdoid tumors of soft tissue, kidney, and CNS, and medullary carcinoma of kidney; subset of epithelioid MPNST, myoepithelial carcinoma of soft tissue, and extraskeletal myxoid chondrosarcoma	Protein correlate of molecular genetic event
p40	Squamous, urothelial, and myoepithelial tumors; myoepithelial/basal cell marker in breast and prostate	Lineage-restricted transcription factor
ATRX (loss)	Diffuse astrocytoma and pancreatic origin of well-differentiated neuroendocrine tumor	Protein correlate of molecular genetic event
SATB2	Colorectal origin of adenocarcinoma, lower GI origin of well-differentiated neuroendocrine tumor, and possibly cutaneous origin of a poorly differentiated neuroendocrine carcinoma; osteoblastic lineage; BCOR-rearranged sarcoma	Lineage-restricted transcription factor
OTP	Bronchopulmonary origin of well-differentiated neuroendocrine tumor	Lineage-restricted transcription factor; identified through gene expression profiling
Rb protein (loss)	Poorly differentiated neuroendocrine carcinoma; spindle cell/pleomorphic lipoma, cellular angiofibroma, and mammary-type myofibroblastoma	Protein correlate of molecular genetic event
SMAD4 (loss)	Pancreatic origin of adenocarcinoma; also frequently lost in colorectal cancer	Protein correlate of molecular genetic event
BAP1 (loss)	Mesothelioma (especially epithelioid) and intrahepatic cholangiocarcinoma; loss in ocular melanoma and renal cell carcinoma prognostically adverse	Protein correlate of molecular genetic event
SF1	Adrenal cortical and sex cord-stromal neoplasms	Lineage-restricted transcription factor
NKX3.1	Prostate cancer	Lineage-restricted transcription factor
INSM1	Neuroendocrine neoplasms	Lineage-restricted transcription factor