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IHC Markers — Complete Immunohistochemistry Guide for Pathology Board Exams

The single reference page for every IHC marker tested on FRCPath, NEET SS, ABPath AP, and FCPS examinations. 150+ markers across 12 organ systems, companion diagnostics, and the exam traps that cost candidates marks.

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IHC Markers

Organ Systems

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Exam Traps

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Jump to CK7/CK20 ↓ Free 199 MCQ PDF

Master CK7/CK20 Panel

The first-line tool for narrowing site of origin in carcinoma of unknown primary. Source: Chu et al., Mod Pathol 2000; PathologyOutlines; Wang et al., Diagnostic Pathology 2025.

CK7+ / CK20+

Urothelial carcinoma (~60%)
Pancreatic adenocarcinoma (subset)
Ovarian mucinous carcinoma (~74%)
Gastric adenocarcinoma (30–50%)
Extrahepatic bile duct / gallbladder
Sinonasal intestinal-type adenocarcinoma

CK7+ / CK20−

Lung adenocarcinoma (non-mucinous)
Breast carcinoma
Serous / endometrioid / clear cell ovarian
Endometrial / endocervical adenocarcinoma
Thyroid carcinoma
Mesothelioma
Cholangiocarcinoma
Salivary gland tumours

CK7− / CK20+

Colorectal adenocarcinoma (80–95%)
Merkel cell carcinoma (perinuclear dot, ~88%)
Some appendiceal mucinous tumours

CK7− / CK20−

Clear cell RCC
Hepatocellular carcinoma
Prostatic adenocarcinoma
Adrenocortical carcinoma
Germ cell tumours (seminoma, embryonal)
Most squamous cell carcinomas (except cervical)

Exam Traps — CK7/CK20 Gastric and pancreatobiliary tumours show high variability — never rely on CK7/CK20 alone for these. CK20 loss in proximal CRC is associated with MSI-H/BRAF-mutated tumours. Cervical SCC is often CK7+ unlike other squamous carcinomas. Papillary and chromophobe RCC are CK7+ (unlike classic clear cell RCC). Always confirm with lineage-specific markers.

Breast Pathology IHC

High Yield ▾

Marker	Pattern	Positive In	Significance
ER	Nuclear	~70–75% breast CA	Positive ≥1% (ASCO/CAP). Predicts endocrine therapy benefit. "Low positive" 1–10%
PR	Nuclear	~60–65% breast CA	Low PR often = Luminal B phenotype
HER2	Membranous	15–20% breast CA	0: no/<10%. 1+: faint >10%. 2+: equivocal→ISH. 3+: intense >10%
Ki-67	Nuclear	Variable %	Cut-offs debated: <5% low, >30% high (IKWG). Luminal A vs B surrogate
E-cadherin	Membranous	Ductal CA	Lost in lobular (CDH1 loss). Up to 15% ILC retains E-cad → use p120
GATA3	Nuclear	85–95% breast	Also + in urothelial. Less sensitive in TNBC
Mammaglobin	Cytoplasmic	70–80% breast	Metastatic workup. Lower sensitivity than GATA3
GCDFP-15	Cytoplasmic	40–60% breast	Apocrine differentiation. Less sensitive in high-grade
SOX10	Nuclear	~30% TNBC	Useful in TNBC/metaplastic. Also + in melanoma (trap)

HER2 Scoring (ASCO/CAP 2023)

Score	Staining Pattern	Interpretation
0	No staining or incomplete faint ≤10%	Negative
1+	Incomplete faint >10%	Negative (but HER2-low for T-DXd)
2+	Weak–moderate complete >10%	Equivocal → reflex to ISH
3+	Intense complete circumferential >10%	Positive

Exam Pearl HER2-low (IHC 1+ or 2+/ISH−) is now clinically relevant for trastuzumab deruxtecan (DESTINY-Breast04 trial) but is NOT an official ASCO/CAP interpretive category. Distinguishing IHC 0 from 1+ now matters clinically — requires 40x magnification.

Molecular Subtypes by IHC Surrogate

Subtype	ER	PR	HER2	Ki-67
Luminal A	+	+	−	Low
Luminal B (HER2−)	+	+/−	−	High
Luminal B (HER2+)	+	+/−	+	High
HER2-enriched	−	−	+	High
Triple-negative / Basal	−	−	−	Very high

Exam Trap E-cadherin retention in ILC: Up to 15% of classic ILC retains E-cadherin. Use p120 catenin — cytoplasmic pattern = lobular, membranous = ductal. ER low positive (1–10%): ~50% behave like TNBC biologically. Mandatory report comment per ASCO/CAP 2020.

Lung Pathology IHC

High Yield ▾

Adenocarcinoma vs Squamous vs Small Cell

Marker	Adenocarcinoma	Squamous	Small Cell
TTF-1	+ (90–95%)	−	+ (~80%)
Napsin-A	+ (80–90%)	−	−
p40	−	+ (95%)	−
CK5/6	−	+	−
Synaptophysin	−	−	+ (90%)
Chromogranin	−	−	+ (80%)
Ki-67	Variable	Variable	Very high (50–100%)

Exam Pearl Minimal panel for poorly differentiated NSCLC: TTF-1 + p40 is often sufficient. p40 is more specific than p63 for squamous differentiation (p63 can be positive in some adenocarcinomas).

Mesothelioma vs Adenocarcinoma

Marker	Mesothelioma	Lung Adenocarcinoma
Calretinin	+ (90%)	−
WT1	+ (75%)	−
D2-40	+	−
TTF-1	−	+ (90%)
Napsin-A	−	+ (80%)
BerEP4	−	+
MOC31	−	+
BAP1	Loss = malignant	Retained

Exam Pearl BAP1 loss in mesothelial proliferation is 100% specific for malignancy — the single most important adjunct in effusion cytology for distinguishing reactive mesothelial cells from mesothelioma.

PD-L1 Scoring

TPS (Tumor Proportion Score): % of viable tumour cells with partial/complete membrane staining. TPS ≥50% → pembrolizumab monotherapy. TPS 1–49% → chemo ± pembrolizumab. TPS <1% → chemo-based.

CPS (Combined Positive Score): Includes tumour + immune cells. Used in gastric, cervical, TNBC, urothelial contexts.

Clones: 22C3 (pembrolizumab), 28-8 (nivolumab), SP263 (durvalumab), SP142 (atezolizumab).

GI & Hepatobiliary IHC

High Yield ▾

Key Entities

Entity	IHC Profile	Notes
Colorectal ADC	CDX2+, CK20+, SATB2+, CK7−	Classic lower GI. SATB2 highly specific
GIST	DOG1+, CD117+, CD34+, desmin−, S100−	DOG1 more sensitive/specific than CD117
HCC	Arginase-1+, HepPar1+, Glypican-3+, canalicular pCEA/CD10	Arginase-1 most specific. CK7/CK20 usually −
Cholangiocarcinoma	CK7+, CK19+, HepPar1−, Arginase-1−	Helps separate from HCC
GI NET	Synaptophysin+, Chromogranin+	Ki-67: G1 <3%, G2 3–20%, G3 >20%

Lynch Syndrome MMR IHC Screening

Test: MLH1, MSH2, MSH6, PMS2. Loss patterns: MLH1/PMS2 loss (most common) → reflex to BRAF V600E and MLH1 methylation to distinguish sporadic vs Lynch. MSH2/MSH6 or isolated MSH6/PMS2 loss → germline testing.

Exam Trap CK7 in proximal colon: 15–40% of right-sided CRC expresses CK7. Never exclude CRC based on CK7 positivity alone. HepPar1 can be positive in gastric tumours — Arginase-1 is more specific for HCC.

Genitourinary IHC

Exam Favourite ▾

Renal Cell Carcinoma Subtypes

RCC Subtype	PAX8	CK7	CAIX	CD10	Other
Clear cell	+	−	+ (membranous)	+	Vimentin+; VHL loss
Papillary	+	+	−/cup	±	AMACR+
Chromophobe	+	+ (diffuse)	−	−	CD117+
TFE3 translocation	+	±	±	+	TFE3+, Cathepsin K+

Prostate: Malignant vs Benign

Malignant: AMACR+, PSA+, NKX3.1+, ERG±. Basal markers p63−, CK5/6−, HMWCK− (absence confirms loss of basal cells = adenocarcinoma).

Germ Cell Tumours

Tumour	OCT4	PLAP	c-KIT	CD30	SALL4	AFP	β-hCG
Seminoma	+	+	+	−	+	−	−
Embryonal CA	+	±	−	+	+	±	±
Yolk sac	−	−	−	−	+	+	−
Choriocarcinoma	−	−	−	±	−	−	+

Exam Pearl AFP elevation = NOT pure seminoma. Even if histology looks like seminoma, elevated serum AFP means search for yolk sac tumour component → reclassify as mixed germ cell tumour.

Gynecologic IHC

Exam Favourite ▾

TCGA/ProMisE Molecular Classification (Endometrial)

Class	Key Test	p53	MMR	Prognosis
POLE ultramutated	POLE sequencing	Wild-type	Intact	Excellent (2–5%)
MMR-deficient	IHC: MLH1/MSH2/MSH6/PMS2	Variable	Deficient	Intermediate (20–30%)
NSMP	Exclusion	Wild-type	Intact	Variable (50–60%)
p53-abnormal	p53 IHC	Mutant	Intact	Worst (15–20%)

Algorithm: MMR IHC → POLE sequencing → p53 IHC.

Key Entities

Endometrial serous: p53 mutant (diffuse/null), ER−, PR−, p16 block+. Endometrioid: ER+, PR+, p53 wild-type, PTEN loss common. High-grade serous ovarian: PAX8+, WT1+, p53 mutant, CK7+, CK20−. Cervical SCC: p16 block+ (HPV), p63+, CK5/6+. Granulosa cell: Inhibin+, calretinin+, SF1+, FOXL2+.

Exam Pearl p16 block positivity means TWO different things: in cervix → HPV-related (Rb pathway). In endometrial serous → p53 pathway (non-HPV). Correlate with p53 IHC and clinical context.

Lymphoma IHC

High Yield ▾

Entity	Key Markers	Key Negatives	Genetics
Classic Hodgkin	CD30+, CD15+, PAX5 dim	CD20−, CD45−	—
NLPHL	CD20+, CD45+, OCT2+, BOB1+	CD30−, CD15−	—
DLBCL	CD20+, CD79a+	—	Hans: CD10/BCL6/MUM1
Follicular	CD20+, CD10+, BCL2+, BCL6+	CD5−	t(14;18)
Mantle cell	CD20+, CD5+, Cyclin D1+, SOX11+	CD23−	t(11;14)
Burkitt	CD20+, CD10+, BCL6+, Ki-67 ~100%	BCL2−	t(8;14) MYC
CLL/SLL	CD20 dim, CD5+, CD23+, LEF1+	Cyclin D1−	—
Hairy cell	CD20+, CD25+, CD103+, Annexin A1+	—	BRAF V600E+
ALCL	CD30+, ALK±, EMA+	—	t(2;5) ALK+

Exam Pearl CD5+ B-cell lymphoma: MCL (CD23−, Cyclin D1+) vs CLL (CD23+, Cyclin D1−). This single distinction appears on almost every pathology board exam. BCL2− in Burkitt distinguishes it from follicular lymphoma (BCL2+). Annexin A1 is the most specific marker for hairy cell leukaemia.

Dermatopathology IHC

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Melanoma: S100+ (95%), SOX10+ (95%), Melan-A+ (80–90%), HMB-45+ (80%). SOX10 has improved specificity over S100. HMB-45 especially useful in epithelioid melanomas.

Merkel cell carcinoma: CK20+ (perinuclear dot), synaptophysin+, TTF-1−. The perinuclear dot CK20 pattern is pathognomonic.

DFSP vs Dermatofibroma: DFSP = CD34+, Factor XIIIa−. Dermatofibroma = CD34−, Factor XIIIa+. Opposite pattern.

BCC: BerEP4+, BCL2+. SCC: p40+, p63+, CK5/6+.

Soft Tissue Sarcoma IHC

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Tumour	Primary Markers	Translocation
Synovial sarcoma	TLE1+, EMA/CK (focal)	t(X;18) SS18-SSX
Solitary fibrous	STAT6+ (nuclear), CD34+	NAB2-STAT6 fusion
WD/DD Liposarcoma	MDM2+, CDK4+ (nuclear)	12q13-15 amplification
Ewing sarcoma	CD99+ (membranous), NKX2-2+	t(11;22) EWSR1-FLI1
Rhabdomyosarcoma	Desmin+, Myogenin+, MyoD1+	PAX3/7-FOXO1 (alveolar)
Leiomyosarcoma	SMA+, Desmin+, h-caldesmon+	No specific fusion
MPNST	S100 (focal), SOX10 (focal)	H3K27me3 loss
Desmoid	Nuclear β-catenin+	CTNNB1 mutation

Exam Pearl — Small Round Blue Cell DDx Ewing = CD99 (membranous) + NKX2-2. Rhabdomyosarcoma = desmin + myogenin. DSRCT = EWSR1-WT1. Lymphoma = CD45 + lineage markers. Neuroblastoma = NB84 + synaptophysin.

Neuropathology IHC (WHO 2021)

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Tumour	IDH1	ATRX	1p/19q	Key Feature
Astrocytoma, IDH-mutant	+	Loss	Intact	Grade 2–4; Grade 4 if CDKN2A/B homdel
Oligodendroglioma	+	Retained	Codeleted	Must have BOTH IDH-mut + 1p/19q codel
Glioblastoma, IDH-wt	−	Variable	Intact	EGFR amp, TERT, +7/−10 (even w/o MVP/necrosis)

Meningioma: EMA+, SSTR2A+, PR±. Schwannoma: S100+, SOX10+ (diffuse). Neurofibroma: S100 (patchy), CD34+ in fibroblasts.

Endocrine IHC

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Papillary thyroid: TTF-1+, thyroglobulin+, CK19+, HBME-1+, BRAF V600E±. Medullary thyroid: Calcitonin+, chromogranin+, CEA+, TTF-1±, thyroglobulin−. Adrenal cortical: SF1+, inhibin+, Melan-A+, CK−/focal. Pheochromocytoma: Synaptophysin+, chromogranin+, GATA3+, S100 in sustentacular cells, CK−. Parathyroid: PTH+, GATA3+, chromogranin±.

Exam Trap TTF-1 is positive in BOTH lung and thyroid. Differentiate with thyroglobulin (thyroid) vs Napsin-A (lung). TTF-1 is also positive in ~80% of small cell carcinoma — including extrapulmonary small cell.

Molecular Markers & Companion Diagnostics

High Yield ▾

Biomarker	Tumour(s)	Therapy	Testing
EGFR	Lung ADC	Osimertinib (3rd gen TKI)	NGS/PCR (IHC not recommended)
ALK	Lung ADC (3–5%)	Alectinib, lorlatinib	IHC (D5F3 = FDA-approved CDx)
ROS1	Lung ADC (1–2%)	Crizotinib, entrectinib	IHC screen → FISH/NGS
BRAF V600E	Melanoma, lung, CRC, thyroid, HCL	Dabrafenib + trametinib	IHC (VE1) or molecular
KRAS G12C	Lung (13%), CRC	Sotorasib, adagrasib	Molecular only (no IHC)
HER2	Breast, gastric, biliary	Trastuzumab, T-DXd	IHC + ISH
NTRK	Pan-cancer (<1%)	Larotrectinib, entrectinib	Pan-TRK IHC screen → NGS
MMR/MSI	CRC, pan-cancer	Pembrolizumab (dMMR)	IHC (4 markers) or PCR/NGS
PD-L1	NSCLC, urothelial, gastric, TNBC	Pembrolizumab, atezolizumab	IHC (22C3, SP263, etc.)
BRCA1/2	Breast, ovarian, pancreatic	Olaparib, niraparib	Germline/somatic NGS
IDH1/2	Glioma, cholangiocarcinoma	Vorasidenib, ivosidenib	IHC (R132H) + NGS
FGFR	Urothelial, CCA	Erdafitinib, pemigatinib	NGS/FISH
Claudin 18.2	Gastric/GEJ (HER2−)	Zolbetuximab	IHC (VENTANA 43-14A)

Common Exam Traps & Pitfalls

Must Know ▾

"Same Marker, Different Tumours"

Marker	Positive In	How to Differentiate
TTF-1	Lung ADC, thyroid CA, ~80% SCLC	Lung: Napsin-A+; Thyroid: thyroglobulin+
PAX8	Renal, thyroid, Müllerian, thymic	Context + CK7/CK20, WT1, ER, thyroglobulin, CAIX
GATA3	Breast (85%), urothelial (85%), parathyroid, pheo	Breast: mammaglobin+; Urothelial: uroplakin+, p63+
CDX2	Colorectal, mucinous ovarian, some gastric	CRC: SATB2+, CK7−; Ovarian: PAX8±, CK7+
CD99	Ewing (membranous), lymphoblastic lymphoma	Ewing: NKX2-2+ (most specific); correlate morphology
WT1	Serous ovarian, mesothelioma	Ovarian: PAX8+, calretinin−; Meso: calretinin+, D2-40+
SOX10	Melanoma, TNBC, nerve sheath tumours	Melanoma: Melan-A+, panCK−; Breast: panCK+, GATA3±

"Unexpected Positive" Markers

Marker	Expected	Unexpected Positive In
Napsin-A	Lung ADC	RCC; clear cell CA of female genital tract
GATA3	Breast, urothelial	Chromophobe RCC (50–80%), parathyroid (70–90%), BCC (80%)
Synaptophysin	NET	Adrenal cortical neoplasms (false NE positive)
CD117	GIST, seminoma	Chromophobe RCC, mastocytosis, AML
Calretinin	Mesothelioma	Adrenal cortical, sex cord-stromal, some breast CA
Inhibin	Sex cord-stromal, adrenal	Trophoblastic tumours (choriocarcinoma)

Technical Pitfalls

HER2 gastric vs breast: Gastric accepts basolateral staining; breast requires complete circumferential. Gastric has marked heterogeneity
SMA staining myofibroblasts: Reactive stromal myofibroblasts around invasive cancer can mimic preserved myoepithelium. Use nuclear markers (p63/p40) or SMMHC instead
Chromophobe RCC vs oncocytoma: Both CD117+. Chromophobe: CK7 diffuse+. Oncocytoma: CK7 scattered/−
Ki-67 counting: Hot-spot vs global counting debate. WHO NET grading recommends hot-spot method, ≥500 cells counted

Practice IHC-Based Questions

This guide covers the markers. Our MCQs test whether you can apply them under exam conditions.

Explore Full Course → Free Board Questions Free 199 MCQ PDF

Sources & References

WHO Classification of Tumours, 5th Edition (all volumes). ASCO/CAP Guidelines: ER/PR (2020), HER2 (2018/2023 update). Chu PG et al. Mod Pathol 2000;13(9):962-972. Hans CP et al. Blood 2004;103(1):275-282. DESTINY-Breast04 (Modi S, N Engl J Med 2022). PathologyOutlines.com. Dabbs DJ, Diagnostic Immunohistochemistry, 6th Ed. CAP/IASLC/AMP Molecular Testing Guidelines.

This guide is for examination preparation. Clinical IHC interpretation should always correlate with morphology, clinical history, and institutional protocols. Sensitivity/specificity figures are approximate ranges from multiple published sources.

Last updated: July 2026 | eLearningFRCPath