Difference between revisions of "Immunohistochemical staining"

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===Prostate vs. bladder===
===Prostate vs. bladder===
Prostate adenocarcinoma vs. urothelial carcinoma:  
Prostate adenocarcinoma vs. urothelial carcinoma:  
*Prostate:PSA +ve, PSAP +ve, AR +ve, CK7 -ve, CK20 -ve.
*Prostate adenocarcioma: PSA +ve, PSAP +ve, AR +ve, CK7 -ve, CK20 -ve.
*Urothelial carcinoma: CK7 +ve, CK20 +ve, PSA -ve, PSAP -ve, AR -ve.
*Urothelial carcinoma: CK7 +ve, CK20 +ve, PSA -ve, PSAP -ve, AR -ve.



Revision as of 15:34, 18 October 2011

Immunohistochemical staining, also immunostaining, is a powerful tool. It is abbreviated IHC.

Utility

Use of IHC:[1]

  1. Unknown primary tumours.
  2. Poorly differentiated tumours.
  3. Prognostic markers, e.g. ERBB2 (HER2).

General (malignant) differential diagnosis

 
 
 
 
 
 
 
 
 
 
Malignancy
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Epithelial
(Carcinoma)
 
Mesenchymal
(Sarcoma)
 
Germ cell
tumour
 
Neuroendocrine
carcinoma
 
Hematologic
 
Malignant
melanoma
  • Carcinoma.
    • AE1/AE3 - pankeratin.
    • Others: EMA, HMWK, LMWK.
  • Sarcoma.
    • Vimentin.
      • Many pathologists think this stain is totally useless.
  • Germ cell tumours.
    • PLAP (placental-like alkaline phosphatase) - not very sensitive.[2]
    • Others: D2-40, OCT 3/4.
  • Neuroendocrine carcinoma.
    • Chromogranin A.
    • Synaptophysin.
    • CD56.
    • CD57.[3]
  • Melanoma.
    • S-100, HMB-45, Melan A (MART-1).
      • Additional (UHN): melanoma cocktail (HMB-45, MART-1)[4], microphthalmia,[5] tyrosinase.[6]
  • Hematologic.
    • Lymphoma/leukemia.
      • CD45 (common leukocyte antigen).
      • CD30.
    • Plasma cell:
      • Kappa.
      • Lambda.
      • CD138.

Keratins

Classification:[7]

  • Low molecular weight keratins (LMWK): 7, 8/18, 19, 20.
  • High molecular weight keratins (HWMK): 4, 10, 13, 14, 17.

Uses:

Organ specific

Thyroid and lung

  • TTF-1 (thyroid transcription factor-1) -- +ve in thyroid gland malignancies.
    • Very good for breast vs. lung.[10]
      • Often negative in squamous cell carcinoma of the lung (as with CK7 & CK20), though HMWK is usually positive.

Image: Adenocarcinoma with nuclear TTF-1 positivity (WC).

Breast markers

  • GCDFP-15 (AKA BRST-2) -- specific, but NOT sensitive.
  • ER (estrogen receptor) - in normal breast.
  • PR (progesterone receptor) - in normal breast.
  • HER2/neu - pathological, assoc. with worse prognosis.

Prostate gland

  • PSA - prostatic specific antigen.
  • PSAP - prostatic specific acid phosphatase.
  • p63 - stains nuclei of basal cell in normal prostate.
  • 34betaE12 - stains basal cells in normal prostate.
  • AMACR (racemase, P504S[11]) - present in adenocarcinoma (NOT in normal prostate).
  • AR - usually present in prostate confined cancers.[12]
  • CAP cocktail - AKA CAP, AKA PIN-4, AKA PIN.

Colorectal carcinoma markers

  • CEA.

Small bowel

  • CDX2.
  • Villin.

Kidney

Renal cell carcinoma:

  • RCC, EMA, CD10.
  • CK7 -ve in clear cell RCC.
  • AMACR +ve in papillary RCC.
  • D2-40 +ve in ChRCC.

Xanthogranulomatous pyelonephritis:

  • CD68 (for macrophages).

Ovary

  • CA125, CK7+, CK20-.
  • WT1 -- 90% in serous +ve.

Serous markers

  • WT-1, CA-125, D2-40.

Liver

HCC vs. cholangiocarcinoma:

  • TTF-1: ~90-100% +ve (cytoplasmic) in HCC vs. ~10% in choleangiocarcinoma.[15]

Mesothelium

  • Calretinin.
  • WT-1.
  • D2-40.
  • CK5/6.

Typically negative:

  • CEA.
  • TTF-1.

Pancreas

Neuropathology

General:

  • S-100.

Glial:

  • GFAP.

Neuronal:

  • Synaptophysin.
  • Chromogranin.

Specific entities:

  • EMA +ve: meningioma, ependymomas (cytoplasm dot-like).[18]

Tumour (low-grade gliomas):

  • IDH-1 +ve.
    • Usually negative in Glioblastoma.

Miscellaneous

Macrophages

  • CD68.

Special:

Special, less common:

One organ vs. another

Cervix vs. uterus

  • Cervix (typically): CEA +ve,[24] p16 +ve.
    • ... and ER -ve, PR -ve, vimentin -ve.
  • Uterus (typically): vimentin +ve, ER +ve, PR +ve.[25]
    • ... and CEA -ve, p16 -ve.

Additional Ref.:[26]

Liver vs. bile duct

Intrahepatic cholangiocarcinoma (ICC) vs. hepatocellular carcinoma (HCC):[27]

  • ICC: CK19 (92.5%), MUC-1 (73.8%) +ve.
  • HCC: HepPar-1 (85.6%), CD34 (87.8%) +ve.

Prostate vs. bladder

Prostate adenocarcinoma vs. urothelial carcinoma:

  • Prostate adenocarcioma: PSA +ve, PSAP +ve, AR +ve, CK7 -ve, CK20 -ve.
  • Urothelial carcinoma: CK7 +ve, CK20 +ve, PSA -ve, PSAP -ve, AR -ve.

Lymphomas

This is covered more extensively in the lymphoma article.

Lymphocytes

  • CD45 (AKA common leukocyte antigen).

B-cells

  • CD20.
  • CD19 (flow only).
  • PAX5.
  • CD79a.

T-cells

  • CD3 - general T-cell marker (marks both CD4 +ve and CD8 +ve cells).
  • CD4.
  • CD8.
  • CD7.
  • CD43.

Specific entities

Follicular lymphoma

  • CD10 +ve, BCL6 +ve.

CLL

  • CD5 +ve, CD23 +ve.

Mantle cell lymphoma

Hodgkin's lymphoma

This is covered more extensively in the Hodgkin lymphoma article.

Classic types:

  • CD30 Reed-Sternberg cells (RSCs) +ve ~98%.[29]
  • CD15 Reed-Sternberg cells +ve ~80%, stains neutrophils.

Germ cell tumours

Seminoma

  • D2-40 +ve.[2]
  • OCT 3/4 +ve.

Embryonal carcinoma

  • CD30 +ve - cytoplasm, cell membrane, Golgi.
    • Rarely positive in seminoma.
  • CK7 +ve.[30]
  • AE1/AE3 +ve.

Yolk sac tumour (endodermal sinus tumour)

  • AFP (alpha fetoprotein).

Choriocarcinoma

  • beta-hCG.

Bare bones mnemonic for GCTs

The germ cell tumour (GCT) IHC mnemonic ABCD:

  • AFP = yolk sac tumour.
  • Beta-hCG = choriocarcinoma.
  • CD30 = embryonal carcinoma.
  • D2-40 = seminoma.

Spindle cell lesions

Abbreviated spindle cell panel (memory device SCADS):

  • S100.
  • CD34.
  • AE1/AE3.
  • Desmin.
  • SMA.

A MFH panel:

Muscle markers

  • Desmin - all three types.
  • H-caldesmon - smooth muscle - most specific.
  • Smooth muscle actin (SMA) - smooth muscle.
  • MyoD1 - skeletal muscle.
  • Smooth muscle myosin (abbreviated SMMS).

Proliferation markers

  • MIB1 - an antibody against the protein Ki-67 (a protein expressed in proliferating cells).

Note: MIB1 should not be confused with mindbomb homolog 1 (MIB-1), a gene that regulates apoptosis.[33]

Carcinomas

CK7 and CK20

CK7+ CK20-

Mnemonic: OBE + lung x2 + H&N x2

CK7- CK20+

CK7+ CK20+

  • Pancreatic adenocarcinoma.
  • Ovary, mucinous subtype.
  • Occasionally gastric adenocarcinoma, cholangiocarcinoma.
  • "Transitional cell carcinoma" (urothelial cell carcinoma).§
  • Esophagus (adenocarcinoma).

Mnemonic: POOTE.

Note:

CK7- CK20-

Mnemonic: NASH TURP.

Vimentin & cytokeratin

A few tumours are positive for both vimentin and cytokeratins.

Common tumours:


Common tumours that uncommonly have the pattern:


Rare tumours:

References

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External links