Comprehensive IHC Antibody Menu for a National Reference Pathology Laboratory
Dako Omnis / Agilent-prioritized, international-standard clones — tiered per subspecialty
Bottom line: A comprehensive national reference IHC menu should run ~340–360 distinct antibodies (well within the ~300–500 range expected of such a center), split into ~110–120 Tier 1 "essential core" markers that carry daily diagnostic volume and ~220–240 Tier 2 "extended reference" markers. Where possible, clone selection below is anchored to NordiQC external-quality-assessment (EQA) performance and, for predictive markers, to FDA/EMA companion-diagnostic pairings and CAP/ASCO-CAP guidance. Because you run Dako Omnis, I flag Agilent/Dako FLEX RTU products that perform well and explicitly flag the several clones NordiQC shows underperform on Omnis (desmin D33, MLH1 ES05 RTU IS079, PAX8 MRQ-50), so you can pre-empt validation failures.
How the tiering and clone recommendations were decided
Primary source for "recommended clone": NordiQC (nordiqc.org) publishes per-clone pass/optimal rates across the three main platforms (Dako/Agilent Omnis, Roche/Ventana BenchMark, Leica Bond). I prefer clones rated sufficient/optimal and note where NordiQC data favors one clone or flags a poor performer.
Predictive/companion markers: follow FDA/EMA assay–drug pairings and CAP/ASCO-CAP guidelines, not just diagnostic performance.
Tier 1 = essential core every high-volume lab must have; Tier 2 = specialized/esoteric markers expected only of a national reference center.
Omnis-specific flags: several clones underperform specifically on Omnis; for those, run the concentrate as an LDT with alkaline HIER (TRS High pH) + 3-step detection, or source the Ventana/Leica RTU.
Quality/validation context for a reference lab
Validation (CAP/CLSI "20/10 rule"): ≥20 positive + ≥20 negative cases for predictive markers (ER, PR, HER2, PD-L1, MMR); ≥10 positive + ≥10 negative for non-predictive markers. Revalidate on any protocol/retrieval/platform change.
EQA: Enroll in NordiQC and/or UK NEQAS ICC & ISH for all predictive and high-impact markers (NordiQC modules: General, Breast, HER2 ISH, Companion).
Controls: on-slide multi-tissue controls including a low-expressor tissue (tonsil+kidney for MMR/EMA, pancreas for CK7/CDX2, testis for NKX3.1/PRAME/OCT3-4).
Accreditation: ISO 15189 is the operative standard; in Turkey, TÜRKAK accreditation to ISO 15189 and TİTCK device registration apply — but the menu itself is built to international standard.
1. Epithelial / carcinoma workup & cytokeratins
Tier 1
Pan-CK
AE1/AE3 (Dako FLEX RTU)
Broad epithelial screen
CK (low MW)
CAM5.2 (CK8/18)
Adenocarcinoma
CK7
OV-TL 12/30 — Dako FLEX RTU GA619 gave highest optimal rate (97%) in NordiQC
Upper-GI/pulmonary/gynae epithelium
CK20
Ks20.8 (Dako FLEX RTU); alt SP33 (Ventana)
Colorectal/urothelial/Merkel
CK5/6
D5/16B4 (Dako) — NordiQC found D5/16 B4 less successful for CK5; RTU XM26 or SP27 performed best
Squamous/mesothelial/myoepithelial
34βE12 / HMW-CK
34βE12 (CK903)
Basal/squamous
p63
DAK-p63 / 4A4
Squamous, myoepithelial, urothelial
EMA / MUC1
E29 (Dako FLEX RTU) — NordiQC most reliable; GP1.4 gave no sufficient results
Epithelial/perineurial/plasma cells
Tier 2
CK8/18
B22.1 & B23.1 / Zym5.2
LMW CK
CK19
RCK108 / b170
Thyroid, HCC differential
CK17 / CK14
E3 / LL002
Squamous/basal subsets
Cadherin-17 (CDH17)
EPR3312
GI adeno, medullary CRC
2. Breast pathology
Tier 1
ER
EP1 (Dako FLEX RTU) — strongest NordiQC performance on Omnis; alt SP1, 1D5
ASCO/CAP; tonsil sensitivity control
PR
PgR636 / PgR 1294 (Dako); alt 1E2 (Ventana), clone 16
ASCO/CAP
HER2 (IHC)
HercepTest mAb clone DG44, GE001 for Dako Omnis — 100% pass, 76–91% optimal in NordiQC; alt 4B5 (Ventana)
ASCO/CAP 2023; DG44 more sensitive for HER2-low
Ki-67
MIB-1 (Dako FLEX RTU); alt 30-9, K2, SP6
All NordiQC-recommendable
GATA3
L50-823 (Ventana RTU best in NordiQC); alt EP368, QR018
Breast/urothelial
E-cadherin
NCH-38 — NordiQC optimal on all platforms; alt EP700
Ductal vs lobular
p63
4A4 / DAK-p63
Myoepithelial
Tier 2
GCDFP-15
23A3 / EP1582Y
Apocrine/mammary
Mammaglobin
304-1A5 / 31A5
Mammary
SOX10
SP267 (Ventana RTU; NordiQC 95% optimal)
Triple-negative/basal, metaplastic
TRPS1 (TRPS2)
EPR16171
Highly sensitive breast lineage incl. TNBC
p120 catenin
6H11 / EP66
Lobular (cytoplasmic) vs ductal
Calponin
CALP
Myoepithelial
SMM-HC
SMMS-1
Myoepithelial
Androgen receptor
AR441 / SP107
Molecular apocrine, TNBC subtyping
3. Gastrointestinal & pancreatobiliary
Tier 1
CDX2
EPR2764Y or DAK-CDX2 (Dako FLEX RTU); also EP25 — NordiQC 97% sufficient
Intestinal lineage
SATB2
EP281 (Ventana RTU most successful 89%; EP281 concentrate weak on Bond/Omnis — use 3-step detection)
Colorectal/appendiceal, osteoblastic
Villin
CWWB1 / ID2C3
Brush-border/GI
DOG1
K9 / SP31
GIST
CD117 (KIT)
DAK-CD117 polyclonal (Dako FLEX RTU) / YR145
GIST, mastocytosis
β-catenin
β-catenin-1
Nuclear in desmoid, solid-pseudopapillary
SMAD4/DPC4
EP618Y / B-8
Loss in pancreatic ductal adeno
Tier 2
HepPar-1
OCH1E5
Hepatocellular
Arginase-1
EPR6672 / polyclonal
More specific hepatocellular
Glypican-3
1G12 / GC33
HCC, yolk sac
Glutamine synthetase
EP164 / GS-6
β-catenin-activated adenoma, HCC
SDHB
21A11AE7
Loss in SDH-deficient GIST
MUC2 / MUC5AC / MUC6
Ccp58 / CLH2 / CLH5
Mucinous subtyping
IMP3 (IGF2BP3)
69.1
Pancreatobiliary/high-grade dysplasia
Maspin
EAW24
Pancreatic ductal adeno (nuclear)
Mesothelin
5B2
Pancreatic/mesothelial
Annexin A10
1-CET-9C10
Pancreatobiliary, gastric foveolar
Cadherin-17
EPR3312
GI lineage
Claudin-18.2
43-14A (see Companion)
zolbetuximab CDx
4. MMR / Lynch & GI predictive
Tier 1
MLH1
ES05 (Dako FLEX RTU & Leica) — best NordiQC pass (94% on Bond); Omnis RTU IS079 dropped performance — calibrate carefully
Predictive/Lynch (20/10 validation)
PMS2
EP51 (Dako/Agilent & Leica RTU 96–100%); avoid Ventana A16-4 RTU — inferior 32% NordiQC
Pairs with MLH1
MSH2
G219-1129 / FE11 (Dako FLEX RTU GA085 93% optimal; Ventana 760-5093 95%)
Pairs with MSH6
MSH6
EP49 / SP93 (NordiQC 90% pass)
Detects isolated MSH6 loss
BRAF V600E
VE1 (Ventana RTU)
Reflex after MLH1 loss; also melanoma/thyroid/HCL
Tier 2
HER2 (gastric)
4B5 (Ventana) / HercepTest
Gastric-specific scoring
Claudin-18.2
43-14A (Ventana RxDx)
see Companion
MMR note
Always run all four; MLH1 M1 clone gives dot-like pattern pitfall (avoid false isolated PMS2 loss)
—
5. Genitourinary
Tier 1
PSA
ER-PR8 / polyclonal (Dako FLEX RTU)
Prostatic
NKX3.1
EP356 (NordiQC 94% pass, all platforms)
More specific/sensitive than PSA for metastatic prostate
AMACR (P504S)
13H4 (Dako RTU 100%) or SP116 (Ventana RTU 100%) — SP116 needs 3-step for optimal
Prostate carcinoma
PIN4 / triple cocktail
4A4 (p63) + 34βE12 + P504S
Basal cell + carcinoma
GATA3
L50-823
Urothelial
PAX8
SP348 (Ventana RTU 100%; NordiQC-preferred) or QR016; avoid MRQ-50 — poor on Omnis/Ventana, cross-reacts with PAX5
Renal/Müllerian/thyroid
ERG
EPR3864
Prostate (fusion), vascular
Tier 2
PSAP
PASE/4LJ
Prostatic (poorly diff.)
Uroplakin II
BC21
Highly specific urothelial
Uroplakin III
AU1 / SP73
Urothelial
S100P
16/f5
Urothelial
Thrombomodulin
1009
Urothelial
CD10
56C6
RCC, others
RCC marker
66.4.C2
Renal
CAIX
EP161 / polyclonal
Clear cell RCC (membranous)
PAX2
EP235
Renal/Müllerian
TFE3
MRQ-37
Xp11 translocation RCC
TFEB
MRQ-52 / polyclonal
t(6;11) RCC
Fumarate hydratase (FH)
J-13
Loss in HLRCC/FH-deficient RCC
2SC
polyclonal
Surrogate for FH deficiency
Cathepsin K
3F9
TFE/TFEB RCC, PEComa
ALK
D5F3 / 5A4
ALK-rearranged RCC
INI1/SMARCB1
MRQ-27
Medullary RCC loss
6. Gynecologic
Tier 1
PAX8
SP348 (Ventana RTU) / QR016
Müllerian/renal/thyroid
WT1
6F-H2 (Dako FLEX RTU)
Serous (diffuse nuclear)
p53
DO-7 (Dako FLEX RTU) — interpret by mutation pattern (wild-type vs aberrant/null); NordiQC pass rates low (~65%), calibrate carefully
Serous/endometrial molecular surrogate
p16
E6H4 (CINtec, Ventana RTU 100% NordiQC); alt JC8 (Dako), 6H12 (Leica)
HPV surrogate; block-type positivity
ER / PR
EP1 / PgR636
see Breast
Napsin A
polyclonal / IP64
Clear cell carcinoma
MMR panel
see Section 4
Endometrial universal screen
Tier 2
HNF-1β
EPR16897 / polyclonal
Clear cell
Vimentin
V9
Endometrioid vs endocervical
PTEN
6H2.1 / Y184
Endometrioid loss
ARID1A (BAF250a)
EPR13501 / D2A8U
Clear cell/endometrioid loss
SALL4
6E3 / EP299
Germ cell
p57 (CDKN1C)
KP10 / 57P06
Complete vs partial hydatidiform mole
hPL
polyclonal
Trophoblast
SF1 / inhibin
N1665 / R1
Sex-cord stromal
7. Pulmonary / thoracic
Tier 1
TTF-1
SPT24 or SP141 — NordiQC: 8G7G3/1 alarmingly low pass (3%, run 46); SPT24 88%, SP141 94%. Trade-off: SPT24/SP141 more sensitive but 8G7G3/1 more specific (less SqCC/mesothelioma cross-staining)
Lung adeno/thyroid
Napsin A
polyclonal / IP64
Lung adeno
p40
BC28 (Dako RTU DAK-p40 100%; NordiQC 94% pass) — avoid polyclonal p40
Squamous (more specific than p63)
CK5/6
D5/16B4 (see caveat) / SP27
Squamous
PD-L1
22C3 (Dako GE006) — see Companion
NSCLC CDx
Tier 2 (incl. mesothelioma panel)
ALK
D5F3 (Ventana CDx)
NSCLC fusion
ROS1
D4D6 (screen) / SP384
Confirm by FISH/NGS
pan-TRK
EPR17341
NTRK fusion screen
Calretinin
DAK-Calret1 / SP65
Mesothelial
WT1
6F-H2
Mesothelial
D2-40 (podoplanin)
D2-40
Mesothelial/lymphatic
BAP1
C-4 (NordiQC dominant clone, ~65% pass concentrate — calibrate); loss = mesothelioma
Nuclear loss
MTAP
EPR6893
Cytoplasmic loss = CDKN2A codeletion surrogate
Claudin-4
3E2C1 / polyclonal — no main-vendor RTU; carcinoma+ / mesothelioma−
Highly specific carcinoma marker
HEG1
SKM9-2 — per Churg et al., Histopathology 2023 (4-lab data): membrane staining in 393/434 (91%) epithelioid/biphasic mesotheliomas vs 1/360 (0.3%) NSCLC (sensitivity 91%, specificity 99.7%)
Mesothelial
DLL3
SP347 (Ventana)
SCLC; tarlatamab context
8. Head & neck, salivary, thyroid, endocrine
Tier 1
p16
E6H4
HPV-associated OPSCC surrogate
SOX10
SP267
Salivary, melanocytic, S100 substitute
S100
polyclonal (Dako FLEX RTU) / 4C4.9
Salivary/nerve
Thyroglobulin
DAK-Tg6 / 2H11+6E1
Thyroid follicular
TTF-1
SPT24 / SP141 (see caveat); 8G7G3/1 for specificity
Thyroid/lung
PAX8
SP348
Thyroid/parathyroid
Calcitonin
polyclonal / SP17
Medullary thyroid
Chromogranin A
LK2H10 (± PHE5), DAK-A3 — NordiQC: LK2H10 most robust
Neuroendocrine
Synaptophysin
MRQ-40 or SNP88 (higher sensitivity than DAK-SYNAP/27G12)
Neuroendocrine
INSM1
MRQ-70 (NordiQC 93% — superior to widely-cited A-8 at 55%)
Neuroendocrine transcription factor
Tier 2
NUT
C52B1
NUT carcinoma
PLAG1
polyclonal / 3B7
Pleomorphic adenoma
HMGA2
polyclonal
Pleomorphic adenoma/lipoma
MYB
EP769Y
Adenoid cystic carcinoma
NR4A3
polyclonal / H-7
Acinic cell carcinoma
pan-TRK
EPR17341
Secretory carcinoma (MASC)
Mammaglobin
304-1A5
Secretory carcinoma
Androgen receptor
AR441 / SP107
Salivary duct carcinoma
DOG1
K9
Acinic cell
Monoclonal CEA
II-7 / COL-1
Medullary thyroid, biliary
PTH
polyclonal
Parathyroid
Insulin / glucagon / somatostatin
polyclonal
Islet/endocrine typing
SF1 (NR5A1)
N1665 / polyclonal
Adrenal cortical, pituitary gonadotroph
Inhibin-α
R1
Adrenal cortical, sex-cord
Melan-A
A103
Adrenal cortical, melanocytic
SDHB
21A11AE7
Paraganglioma/pheo syndromic loss
Parafibromin (CDC73)
2H1
Loss in parathyroid carcinoma
PIT1 / TPIT / SF1
—
Pituitary lineage typing
9. Hematopathology
Tier 1
CD3
polyclonal A0452 / LN10 / F7.2.38 (Dako FLEX RTU) — HIER mandatory
T cells
CD20
L26 (Dako FLEX RTU; Leica/Ventana RTU 100% NordiQC)
B cells
CD79a
JCB117
B cells (incl. post-rituximab)
PAX5
DAK-PAX5 (NordiQC most robust; avoid SP34 — aberrant staining)
B lineage
CD5
4C7
T cells, CLL/MCL
CD10
56C6
GC, FL, BL
BCL2
124 (Dako) / E17
FL, DLBCL
BCL6
PG-B6p or LN22 (Dako Omnis RTU best; GI191E/A8 Ventana poorer signal-to-noise)
GC
MYC
Y69
High-grade/double-hit
Cyclin D1
EP12 / SP4 (NordiQC 95% pass)
MCL, HCL, myeloma
CD30
Ber-H2
HL, ALCL, embryonal
CD15
Carb-3 / MMA
HL
Ki-67
MIB-1
Proliferation
Kappa / Lambda
polyclonal IHC + mRNA ISH
Plasma cell clonality (ISH preferred)
Tier 2
SOX11
MRQ-58
Cyclin D1-neg MCL
CD23
DAK-CD23 / SP23
CLL, FDC
LEF1
EP310
CLL
CD138
MI15
Plasma cells
MUM1/IRF4
MUM1p (Dako GA644 100%, 98% optimal NordiQC)
Plasma cell/ABC-DLBCL
ALK1
ALK1 / D5F3
ALCL
TdT
polyclonal / SEN28
Lymphoblastic
CD34
QBEnd/10
Blasts, vascular
CD117
polyclonal / YR145
Mast cells, AML
MPO
polyclonal
Myeloid
CD68
PG-M1 / KP1
Histiocytes
CD163
MRQ-26 / 10D6
Histiocytes
Lysozyme
polyclonal
Myelomonocytic
CD21 / CD23
1F8 / DAK-CD23
FDC meshworks
CD4 / CD8 / CD7 / CD2
4B12 / C8/144B / CBC.37 / AB75
T-subset
CD56
123C3 / MRQ-42
NK/T, plasma cell, NE
TIA-1 / granzyme B / perforin
2G9 / GrB-7 / 5B10
Cytotoxic
EBV LMP1 + EBER-ISH
CS.1-4 + EBER ISH
EBER ISH is gold standard
HHV8/LANA
13B10
KS, PEL, Castleman
PD-1
NAT105
TFH, follicular
PD-L1
22C3 / 28-8
cHL, therapy
CD25
4C9
HCL, ATLL
CD123
6H6 / polyclonal
pDC, BPDCN, HCL
TCL1
27D6
pDC, CLL
Annexin A1
EP75
HCL
BRAF VE1
VE1
HCL
Langerin/CD207
12D6
LCH
CD1a
O10 / EP3622
LCH, cortical thymocytes
S100
polyclonal
LCH, RDD, histiocytoses
IgG4 / IgG
polyclonal
IgG4-RD ratio
Tryptase
AA1
Mast cells/mastocytosis
ERG
EPR3864
Vascular/endothelial
10. Soft tissue & bone
Tier 1
SMA
1A4
Myoid
Desmin
D33 (Dako FLEX RTU) — NOT recommended on Dako Omnis per NordiQC; use DE-R-11 with HIER (not enzymatic) on Omnis
Myogenic
h-caldesmon
h-CD / E89
Smooth muscle vs myofibroblast
Myogenin
F5D
Rhabdomyosarcoma
MyoD1
EP212 / 5.8A
Rhabdomyosarcoma
S100
polyclonal / 4C4.9
Nerve sheath, cartilage
SOX10
SP267 (NordiQC 92% pass)
Nerve sheath, melanocytic
CD34
QBEnd/10
SFT, DFSP, vascular
STAT6
YE361 / EP325
Solitary fibrous tumor (nuclear)
Ki-67
MIB-1
Grading
β-catenin
β-catenin-1
Desmoid (nuclear)
Tier 2
MUC4
8G7
Synovial sarcoma, LGFMS
TLE1
EPR9060 / 1F5
Synovial sarcoma
INI1/SMARCB1
MRQ-27 / 25
Loss: epithelioid sarcoma, rhabdoid
BRG1/SMARCA4
EPNCIR111A
Loss: SMARCA4-deficient tumors
ALK
D5F3 / 5A4
IMT
ROS1
D4D6
IMT subset
pan-TRK
EPR17341
NTRK sarcoma, LFN tumor
CD99
12E7 / O13
Ewing (membranous)
NKX2.2
EP336
Ewing
FLI1
MRQ-1
Ewing, vascular
ERG
EPR3864
Vascular, Ewing subset
CAMTA1
polyclonal
Epithelioid hemangioendothelioma
TFE3
MRQ-37
ASPS, PEComa
WT1 (C-terminus)
6F-H2
DSRCT
H3K27me3
polyclonal / C36B11
MPNST loss
H3G34W
RM263
Giant cell tumor of bone
H3K36M
RM193
Chondroblastoma
SATB2
EP281
Osteosarcoma, osteoblastic
Brachyury (TBXT)
EPR18113
Chordoma
MDM2
IF2 / SMP14
WD/DD liposarcoma — confirm by FISH; IHC imperfect
CDK4
DCS-31
WD/DD liposarcoma (with MDM2)
Rb1
13A10 / G3-245
Spindle cell/pleomorphic lipoma loss
PAX7
EPR20353
Rhabdomyosarcoma, Ewing
DOG1
K9
GIST
HHV8/LANA
13B10
Kaposi
GLUT1
polyclonal / SPM498
Perineurioma, hemangioma
EMA / claudin-1
E29 / polyclonal
Perineurioma
11. Neuropathology
Tier 1
GFAP
GA5 / polyclonal (Dako FLEX RTU)
Glial
OLIG2
EPR2673 / 211F1.1
Glial lineage
IDH1 R132H
H09 (Dianova; field standard); alt MRQ-67 (less background)
Diffuse glioma; WHO CNS5 first step
ATRX
polyclonal / BSB-108
Loss in astrocytoma
p53
DO-7
Astrocytoma pattern
Ki-67
MIB-1
Grading
Synaptophysin
MRQ-40 / SNP88
Neuronal/neurocytic
Tier 2
H3 K27M
RM192 / polyclonal
Diffuse midline glioma
H3K27me3
C36B11
Loss in DMG, MPNST
BRAF VE1
VE1
PXA, ganglioglioma, PA
EMA
E29
Meningioma, ependymoma (dot)
SSTR2A
UMB-1
Meningioma, NET
Progesterone receptor
PgR636
Meningioma
STAT6
YE361
Solitary fibrous tumor/HPC
NeuN
A60
Neuronal
Chromogranin A
LK2H10
Neuroendocrine
INI1/SMARCB1
MRQ-27
AT/RT loss
L1CAM
UJ127
Ependymoma (ZFTA/RELA)
LIN28A
polyclonal
ETMR
β-catenin
β-catenin-1
WNT medulloblastoma, craniopharyngioma
Transthyretin
polyclonal
Choroid plexus
PIT1 / TPIT / SF1
—
Pituitary lineage
Pituitary hormones (GH, PRL, ACTH, TSH, FSH, LH)
—
Adenoma typing
Neurofilament
2F11
Axonal preservation
Phospho-tau (AT8)
AT8
Neurodegeneration/autopsy
β-amyloid
6F/3D
Alzheimer/CAA
α-synuclein
KM51 / 5G4
Lewy body
TDP-43 (phospho)
1D3 / polyclonal
FTLD/ALS
12. Dermatopathology & melanocytic
Tier 1
S100
polyclonal / 4C4.9
Melanocytic screen
SOX10
SP267
Melanocytic/nerve
Melan-A
A103
Melanocytic
HMB-45
HMB-45
Melanocytic (junctional gradient)
PRAME
EPR20330 (NordiQC 80% pass, optimal on all platforms)
Malignant melanocytic (nuclear)
Ki-67
MIB-1
Proliferation
BerEP4
Ber-EP4
BCC
p16
E6H4
Spitzoid/melanoma context
Tier 2
Tyrosinase
T311
Melanocytic
MITF
D5 / C5
Melanocytic (nuclear)
BAP1
C-4
BAP1-inactivated melanocytic tumor loss
β-catenin / LEF1
β-catenin-1 / EP310
Deep penetrating nevus
EMA
E29
Paget, sebaceous, epithelioid
CEA
polyclonal / II-7
Paget/EMPD
CK7
OV-TL 12/30
Paget/EMPD
GCDFP-15
23A3
Mammary Paget
Adipophilin
polyclonal
Sebaceous
Androgen receptor
AR441 / SP107
Sebaceous
CD34
QBEnd/10
DFSP (vs DF)
Factor XIIIa
AC-1A1 / EP3372
Dermatofibroma
ERG / CD31
EPR3864 / JC70A
Angiosarcoma
MYC
Y69
Post-radiation/secondary angiosarcoma (amplified)
CD123
6H6
Lupus (pDC clusters)
13. Renal medical / nephropathology & transplant
Tier 1
IgA / IgG / IgM
polyclonal (Dako)
Immune-complex GN panel
C3 / C1q
polyclonal
Complement deposition
C4d
SP91 (Cell Marque rmAb) or polyclonal
Antibody-mediated rejection (peritubular capillaries)
Kappa / Lambda
polyclonal
Light-chain restriction (myeloma cast, MIDD)
Albumin / Fibrinogen
polyclonal
Panel completeness
SV40 large T
MRQ-4 or PAb416
BK polyomavirus nephropathy (nuclear)
Tier 2
PLA2R
polyclonal (Sigma HPA012657)
Primary membranous nephropathy (granular GBM)
THSD7A
polyclonal (Sigma HPA000923)
PLA2R-negative membranous
DNAJB9
rabbit polyclonal (Thermo/Invitrogen)
Fibrillary GN (sensitive/specific; can replace EM)
14. Infectious disease IHC
Tier 1
CMV
DDG9 + CCH2 cocktail (Dako)
Inclusions
HSV1/2
polyclonal (Dako)
Herpetic
Helicobacter pylori
polyclonal (Cell Marque/Dako) or BC7
Gastric
EBV (EBER-ISH)
EBER ISH probe
Gold standard for EBV
Tier 2
Adenovirus
2/6 + 20/11 cocktail
Enteric/pulmonary
SV40/BK
MRQ-4 / PAb416
Polyomavirus
Treponema pallidum
polyclonal
Syphilis (superior to silver)
Spirochetes / Borrelia
polyclonal
—
Mycobacteria
polyclonal (BCG)
Adjunct to AFB
Fungal
anti-Aspergillus/Candida
Adjunct to GMS/PAS
Toxoplasma gondii
polyclonal
Tachyzoites/bradyzoites
HHV8/LANA
13B10
KS
Parvovirus B19
R92F6
Aplastic/hydrops
SARS-CoV-2 (N protein)
polyclonal / 1A9
Research/autopsy
15. Neuroendocrine & paraganglioma across sites
Confirm NE differentiation: synaptophysin (MRQ-40/SNP88), chromogranin A (LK2H10), INSM1 (MRQ-70).
Site of origin: CDX2 (midgut), TTF-1 (lung/thyroid — clone caveat), Islet-1 (pancreatic/duodenal), SATB2 (rectal/appendiceal).
SSTR2A (UMB-1): theranostic (SSA/PRRT) + diagnostic.
Ki-67 (MIB-1): mandatory for WHO grading — per WHO 2019 GEP-NEN classification: well-differentiated NET G1 Ki-67 <3% (<2 mitoses/2 mm²), G2 3–20%, G3 >20%, distinct from poorly-differentiated NEC.
SDHB (21A11AE7): loss flags SDH-deficient paraganglioma/pheochromocytoma syndromes.
GATA3 (L50-823): head/neck parasympathetic paraganglioma (with tyrosine hydroxylase, keratin-negativity).
16. Cancer of unknown primary (CUP) — algorithmic core
First tier: pan-CK, CK7/CK20, TTF-1, CDX2, GATA3, PAX8, p40, ER, S100/SOX10, synaptophysin/chromogranin. Second tier by pattern: NKX3.1 (prostate), napsin A (lung/clear cell), WT1 (serous/mesothelial), SATB2 (colorectal), arginase-1/HepPar-1 (hepatocellular), GCDFP-15/mammaglobin/TRPS1 (breast), SALL4/OCT3-4 (germ cell), melan-A/inhibin/SF1 (adrenal). GATA3 + PAX8 + TTF-1 + CDX2 resolves the majority of epithelial CUPs.
17. Germ cell tumors
SALL4
6E3 / EP299
Pan-germ cell (most sensitive)
OCT3/4
C-10 (NordiQC optimal)
Seminoma/embryonal (nuclear)
CD30
Ber-H2
Embryonal carcinoma
Glypican-3
1G12
Yolk sac, choriocarcinoma
AFP
polyclonal
Yolk sac
hCG (β)
polyclonal
Choriocarcinoma/syncytiotrophoblast
CD117
polyclonal
Seminoma/dysgerminoma
D2-40
D2-40
Seminoma
SOX2
SP76
Embryonal (vs seminoma)
SOX17
polyclonal
Seminoma/yolk sac
PLAP
8A9
Classic germ cell
18. Pediatric small round blue cell tumors
WT1 (6F-H2; C-terminus for DSRCT), desmin (dot-like in DSRCT/RMS), myogenin/MyoD1 (RMS), CD99 (12E7) + NKX2.2 (EP336) + FLI1 (Ewing), PHOX2B (neuroblastoma — highly specific), INI1/SMARCB1 (rhabdoid loss), LIN28A (ETMR/germ cell), glypican-3 + β-catenin (hepatoblastoma), SALL4.
19. Mesothelial / serosal & body-cavity cytology
Carcinoma: MOC31, claudin-4, BerEP4.
Mesothelial: calretinin, WT1, D2-40, HEG1 (SKM9-2), CK5/6.
Malignancy within mesothelial proliferation: BAP1 loss + MTAP loss (CDKN2A surrogate).
Efficient two-stain approach: HEG1+/claudin-4− = mesothelioma; claudin-4+/HEG1− = carcinoma (caution when high-grade serous carcinoma is in the differential — mesothelial markers can stain it).
20. Predictive / companion & theranostic markers (consolidated)
PD-L1 (assay–drug pairing; each assay tied to its own platform + scoring)
22C3 pharmDx (GE006, Dako/Agilent) — NordiQC strongest (98% pass, 92% optimal)
Dako ASL48
Pembrolizumab; NSCLC, gastric, cervical, H&N, esophageal, TNBC
TPS (lung), CPS (others)
28-8 pharmDx (Dako)
Dako
Nivolumab (complementary)
TC/TPS
SP263 (Ventana)
BenchMark
Durvalumab/atezolizumab; NSCLC, urothelial
TPS/CPS
SP142 (Ventana) — lowest sensitivity, non-interchangeable
BenchMark
Atezolizumab; TNBC (IC), NSCLC
IC% (TNBC), TC/IC
Blueprint project: 22C3/28-8/SP263 are concordant on tumor-cell staining; SP142 stains consistently fewer cells. Do not interchange assay + scoring algorithm.
HER2
Breast: HercepTest mAb DG44 (GE001, Dako Omnis) or 4B5 (Ventana); ASCO/CAP 2023. HER2-low — per Modi et al., NEJM 2022 (DESTINY-Breast04): ~60% of HER2-negative metastatic breast cancers express low HER2, defined as IHC 1+, or IHC 2+ with negative ISH; the trial used the VENTANA HER2/neu (4B5) assay (response rate 52.3% with trastuzumab deruxtecan). Reproducibility of 1+ vs 0 is the weak point (NordiQC flags decreased HER2-low concordance).
Gastric: 4B5/HercepTest with gastric-specific scoring.
ER / PR
EP1 (ER) / PgR636 (PR); ASCO/CAP 2020 — ≥1% positive is positive; tonsil sensitivity control; report % and intensity.
MMR
MLH1 ES05, PMS2 EP51, MSH2 FE11/G219-1129, MSH6 EP49 — four-antibody panel; dMMR → immunotherapy eligibility + Lynch screen.
Other established CDx / theranostic
ALK
D5F3 (VENTANA ALK CDx)
NSCLC — crizotinib/alectinib; dichotomous
ROS1
D4D6 (screen) / SP384
Confirm fusion by FISH/NGS
pan-TRK
EPR17341 (Ventana)
NTRK fusion screen; confirm by NGS
BRAF V600E
VE1
Melanoma, thyroid, CRC, HCL, LCH
IDH1 R132H
H09
Glioma
Claudin-18.2
43-14A (VENTANA CLDN18 RxDx)
Gastric/GEJ — zolbetuximab; positive = ≥75% of tumor cells with moderate-to-strong (2+/3+) membranous staining (SPOTLIGHT/GLOW; ~38.4% of screened patients positive)
FOLR1 (FRα)
FOLR1-2.1 (VENTANA FOLR1 RxDx)
Ovarian — mirvetuximab soravtansine; high FRα by PS2+ = ≥75% of viable tumor cells at 2+/3+ intensity (MIRASOL, NEJM 2023)
c-MET
SP44 (VENTANA MET RxDx)
NSCLC — telisotuzumab vedotin (Emrelis, FDA accelerated approval May 14 2025); MET-high = ≥50% of tumor cells with strong (3+) staining (intermediate = 25–<50% 3+; LUMINOSITY)
TROP2
EPR20043 (Ventana)
Sacituzumab govitecan — IHC not yet a validated selector
DLL3
SP347 (Ventana)
SCLC — tarlatamab context; emerging/RUO, not a required CDx
HER3 (ERBB3)
RTJ.2 / DAK-H3-IC
Investigational (patritumab deruxtecan)
NECTIN-4
no validated clone
Enfortumab vedotin given without IHC selection
EGFR mutation-specific
L858R (43B2), E746-A750del (6B6/D6B6)
Adjunct only — limited/variable sensitivity; molecular is gold standard
Relevant ISH (adjuncts)
HER2 DISH/FISH (Ventana dominant), EBER-ISH (EBV gold standard), kappa/lambda mRNA ISH (plasma-cell clonality, superior to IHC), albumin mRNA ISH (hepatocellular), high-risk HPV RNA ISH (OPSCC/cervix — more specific than p16 alone).
21. Approximate antibody count summary
Cytokeratins/epithelial
8
4
12
Breast
7
8
15
GI & pancreatobiliary
7
12
19
MMR & GI predictive
5
3
8
Genitourinary
7
17
24
Gynecologic
7
8
15
Pulmonary/thoracic
5
12
17
H&N/salivary/thyroid/endocrine
11
20
31
Hematopathology
14
33
47
Soft tissue & bone
11
27
38
Neuropathology
7
22
29
Dermatopathology
8
16
24
Nephropathology
6
3
9
Infectious disease
4
11
15
Germ cell
—
11
11
Pediatric SRBCT (new)
—
~6
6
Companion/theranostic (unique)
~8
~10
18
Approximate total (deduplicated)
~340–360 distinct antibodies
This places the menu squarely in the ~300–500 range expected of a comprehensive national reference laboratory. Roughly 110–120 Tier 1 antibodies carry the vast majority of daily diagnostic volume; the ~220–240 Tier 2 additions provide reference-center breadth.
Recommendations (staged, with change thresholds)
Phase 1 — core (~120 Tier 1): Stand up all Tier 1 panels first; prioritize predictive markers (ER/PR/HER2/MMR/PD-L1 22C3) with full 20/10 validation and NordiQC enrollment before clinical sign-out. Benchmark: NordiQC "sufficient" (ideally "optimal") on each before go-live.
Phase 2 — reference breadth: Add Tier 2 by expected referral volume. Highest reference-center value: hematopathology, soft tissue, and neuropathology panels (largest esoteric-marker counts and the markers other labs most often refer out).
Omnis-specific validation (do this proactively): For clones NordiQC flags as weak on Omnis — desmin D33, MLH1 ES05 RTU (IS079), PAX8 MRQ-50 — either validate the concentrate as an LDT with alkaline HIER (TRS High pH) + 3-step detection, or source the Ventana/Leica RTU. Similarly plan 3-step detection for SATB2 (EP281), AMACR (SP116), and BCL6.
Theranostic governance: Tie each PD-L1 clone to its drug + scoring algorithm; never substitute. Onboard CDx assays (claudin-18.2 43-14A, FOLR1-2.1, MET SP44) as the corresponding drugs gain local (TİTCK) approval. Treat TROP2/DLL3/HER3/NECTIN-4 as investigational until validated selection assays exist.
Revalidation triggers (thresholds that change the plan): any NordiQC "insufficient" result, a platform or antibody-lot change, a new WHO classification edition, or a new companion-drug approval → revalidate the affected assay.
Caveats
NordiQC pass rates are platform- and protocol-dependent; a "recommended clone" still requires local calibration. Several clones (SATB2 EP281, AMACR SP116, BCL6, several MMR RTUs) need a 3-step detection system for optimal results.
Several clones underperform specifically on Dako Omnis despite being field standards elsewhere (desmin D33, MLH1 ES05 RTU IS079) — this is the single biggest platform-specific risk for your lab.
p53 and PAX8 have persistently low NordiQC pass rates; invest in calibration and interpret p53 by mutation-pattern (wild-type / overexpressed / null), not simple positive-negative.
MDM2/CDK4 IHC is imperfect — confirm liposarcoma by MDM2 FISH. Likewise ALK/ROS1/pan-TRK IHC are screens; confirm fusions molecularly.
Emerging theranostic markers (TROP2, DLL3, HER3, NECTIN-4) lack validated FDA companion-diagnostic IHC assays — treat as investigational and do not use for treatment selection outside trials.
Polyclonal antibodies remain field standard where no monoclonal RTU exists (PLA2R, THSD7A, DNAJB9, claudin-4, several infectious-disease markers) but require careful specificity validation.
Clone vendor-sourcing shifts over time (e.g., HHV8 13B10 moved Leica→Cell Marque; C4d available as both SP91 mAb and polyclonal) — verify current availability and validate the specific lot/product locally.
In this section
Last updated