Difference between revisions of "Immunohistochemical staining"

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==Organ specific==
==Organ specific==
===Thyroid===
===Thyroid===
*TTF-1 (thyroid transcription factor-1).
*TTF-1 ([[thyroid]] transcription factor-1) -- +ve in thyroid gland malignancies.
**Very good for breast vs. lung.<ref name=pmid18318581>{{cite journal |author=Jagirdar J |title=Application of immunohistochemistry to the diagnosis of primary and metastatic carcinoma to the lung |journal=Arch. Pathol. Lab. Med. |volume=132 |issue=3 |pages=384–96 |year=2008 |month=March |pmid=18318581 |doi= |url=http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0003-9985&volume=132&page=384}}</ref>
**Very good for [[breast]] vs. [[lung]].<ref name=pmid18318581>{{cite journal |author=Jagirdar J |title=Application of immunohistochemistry to the diagnosis of primary and metastatic carcinoma to the lung |journal=Arch. Pathol. Lab. Med. |volume=132 |issue=3 |pages=384–96 |year=2008 |month=March |pmid=18318581 |doi= |url=http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0003-9985&volume=132&page=384}}</ref>
***Negative in squamous cell carcinoma of the lung (as with CK7 & CK20), though HMWK is usually positive.
***Negative in squamous cell carcinoma of the lung (as with CK7 & CK20), though HMWK is usually positive.


===Breast markers===
===[[Breast]] markers===
*GCDFP-15 (aka BRST2) -- specific, but NOT sensitive.
*GCDFP-15 (aka BRST2) -- specific, but NOT sensitive.
*ER (estrogen receptor) - in normal breast.
*ER (estrogen receptor) - in normal breast.
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*PSA - prostatic specific antigen.
*PSA - prostatic specific antigen.
*PSAP - prostatic specific acid phosphatase.
*PSAP - prostatic specific acid phosphatase.
*p63 - stains nuclei of basal cell in normal prostate.
*p63 - stains nuclei of basal cell in normal [[prostate]].
*34betaE12 - stains basals cells in normal prostate.
*34betaE12 - stains basals cells in normal prostate.
*AMACR (racemase, P504S<ref>[http://www.antibodies-online.com/antibody/125649/P504S+alphaMethylacylCoA+Racemace+AMACR+Human/ http://www.antibodies-online.com/antibody/125649/P504S+alphaMethylacylCoA+Racemace+AMACR+Human/]</ref>) - present in adenocarcinoma (NOT in normal prostate).
*AMACR (racemase, P504S<ref>[http://www.antibodies-online.com/antibody/125649/P504S+alphaMethylacylCoA+Racemace+AMACR+Human/ http://www.antibodies-online.com/antibody/125649/P504S+alphaMethylacylCoA+Racemace+AMACR+Human/]</ref>) - present in adenocarcinoma (NOT in normal prostate).
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*AFP (alpha-fetaprotein).
*AFP (alpha-fetaprotein).
*Glypican-3.
*Glypican-3.
**HCC stains with glypican 3, while liver with dysplastic changes and/or [[cirrhosis|cirrhotic changes]] does not.<ref>{{cite journal  | author=Anatelli F, Chuang ST, Yang XJ, Wang HL. |title=Value of glypican 3 immunostaining in the diagnosis of hepatocellular carcinoma on needle biopsy |journal=Am J Clin Pathol. |volume=130 |issue= 2 |pages= 219-23? |year= 2008 |pmid= 18628090 |doi= 10.1309/WMB5PX57Y4P8QCTY }}</ref>
**HCC stains with glypican 3, while [[liver]] with dysplastic changes and/or [[cirrhosis|cirrhotic changes]] does not.<ref>{{cite journal  | author=Anatelli F, Chuang ST, Yang XJ, Wang HL. |title=Value of glypican 3 immunostaining in the diagnosis of hepatocellular carcinoma on needle biopsy |journal=Am J Clin Pathol. |volume=130 |issue= 2 |pages= 219-23? |year= 2008 |pmid= 18628090 |doi= 10.1309/WMB5PX57Y4P8QCTY }}</ref>
*HepPar-1 (hepatocytes paraffin antibody 1) - labels hepatocellular mitochondria.<ref name=pmid12502967>The diagnostic value of hepatocyte paraffin antibody 1 in differentiating hepatocellular neoplasms from nonhepatic tumors: a review. Lamps LW, Folpe AL. Adv Anat Pathol. 2003 Jan;10(1):39-43. Review. PMID 12502967.</ref>
*HepPar-1 (hepatocytes paraffin antibody 1) - labels hepatocellular mitochondria.<ref name=pmid12502967>The diagnostic value of hepatocyte paraffin antibody 1 in differentiating hepatocellular neoplasms from nonhepatic tumors: a review. Lamps LW, Folpe AL. Adv Anat Pathol. 2003 Jan;10(1):39-43. Review. PMID 12502967.</ref>


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===Pancreas===
===Pancreas===
*CK17 - approx. 50% of pancreaticobiliary adenocarcinomas & patchy.<ref name=pmid11345833>{{cite journal |author=Goldstein NS, Bassi D |title=Cytokeratins 7, 17, and 20 reactivity in pancreatic and ampulla of vater adenocarcinomas. Percentage of positivity and distribution is affected by the cut-point threshold |journal=Am. J. Clin. Pathol. |volume=115 |issue=5 |pages=695–702 |year=2001 |month=May |pmid=11345833 |doi=10.1309/1NCM-46QX-3B5T-7XHR |url=}}</ref>
*CK17 - approx. 50% of [[pancreas|pancreatico]]biliary adenocarcinomas & patchy.<ref name=pmid11345833>{{cite journal |author=Goldstein NS, Bassi D |title=Cytokeratins 7, 17, and 20 reactivity in pancreatic and ampulla of vater adenocarcinomas. Percentage of positivity and distribution is affected by the cut-point threshold |journal=Am. J. Clin. Pathol. |volume=115 |issue=5 |pages=695–702 |year=2001 |month=May |pmid=11345833 |doi=10.1309/1NCM-46QX-3B5T-7XHR |url=}}</ref>
*CK19.<ref name=pmid18318589>{{cite journal |author=Geller SA, Dhall D, Alsabeh R |title=Application of immunohistochemistry to liver and gastrointestinal neoplasms: liver, stomach, colon, and pancreas |journal=Arch. Pathol. Lab. Med. |volume=132 |issue=3 |pages=490–9 |year=2008 |month=March |pmid=18318589 |doi= |url=}}</ref>
*CK19.<ref name=pmid18318589>{{cite journal |author=Geller SA, Dhall D, Alsabeh R |title=Application of immunohistochemistry to liver and gastrointestinal neoplasms: liver, stomach, colon, and pancreas |journal=Arch. Pathol. Lab. Med. |volume=132 |issue=3 |pages=490–9 |year=2008 |month=March |pmid=18318589 |doi= |url=}}</ref>


Revision as of 01:51, 24 July 2010

Immunohistochemical staining is a godsend. It helps when ya can't quite figure it out from the histology or with conventional stains.

General (malignant) differential diagnosis

 
 
 
 
 
 
 
 
 
 
Malignancy
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Epithelial
(Carcinoma)
 
Mesenchymal
(Sarcoma)
 
Germ cell
tumour
 
Neuroendocrine
carcinoma
 
Lymphoid
(Lymphoma)
 
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.[1]
    • Others: D2-40, OCT 3/4.
  • Neuroendocrine carcinoma.
    • Chromogranin.
    • Synaptophysin.
    • CD56.
  • Melanoma.
    • S-100, HMB-45, Melan A (MART-1).
  • Lymphoma/leukemia.
    • CD45 (common leukocyte antigen).

Keratins

Classification:[2]

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

Uses:

  • CK8 (CAM5.2)[3] - used to look for mets from breast cancer in axillary lymph nodes.
  • HWMK - squamous cell carcinoma.

Organ specific

Thyroid

  • TTF-1 (thyroid transcription factor-1) -- +ve in thyroid gland malignancies.
    • Very good for breast vs. lung.[4]
      • Negative in squamous cell carcinoma of the lung (as with CK7 & CK20), though HMWK is usually positive.

Breast markers

  • GCDFP-15 (aka BRST2) -- specific, but NOT sensitive.
  • ER (estrogen receptor) - in normal breast.
  • PR (progesterone receptor) - in normal breast.
  • HER2/neu - pathological, assoc. with worse prognosis.
    • HER2/neu+ cancers Tx'ed with trastuzumab (Herceptin).

Prostate

  • PSA - prostatic specific antigen.
  • PSAP - prostatic specific acid phosphatase.
  • p63 - stains nuclei of basal cell in normal prostate.
  • 34betaE12 - stains basals cells in normal prostate.
  • AMACR (racemase, P504S[5]) - present in adenocarcinoma (NOT in normal prostate).
  • CAP cocktail - AKA CAP (AMACR p63 and 34βE12).

CRC 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

  • AFP (alpha-fetaprotein).
  • Glypican-3.
  • HepPar-1 (hepatocytes paraffin antibody 1) - labels hepatocellular mitochondria.[7]

HCC vs. cholangiocarcinoma:

  • TTF-1: ~90-100% +ve (cytoplasmic) in HCC vs. ~10% in choleangiocarcinoma.[8]

Mesothelium

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

Typically negative:

  • CEA.
  • TTF-1.

Macrophages

  • CD68.
  • CD1a -- +ve in Langerhans histocytes.

Less common:

Pancreas

One organ vs. another

Cervix vs. uterus

  • Cervix (typically): CEA +ve,[12] p16 +ve.
    • ... and ER -ve, PR -ve, vimentin -ve.
  • Uterus (typically): vimentin +ve, ER +ve, PR +ve.[13]
    • ... and CEA -ve, p16 -ve.

Additional Ref.:[14]

Liver vs. bile duct

Intrahepatic cholangiocarcinoma (ICC) vs. hepatocellular carcinoma (HCC):[15]

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

Lymphomas

Lymphocytes

  • CD45 (AKA common leukocyte antigen).

B-cells

  • CD20.
  • CD19 (flow only).

Follicular lymphoma:

  • CD10+, bcl-6+.

CLL:

  • CD5+, CD23+.

Mantle cell lymphoma:

  • Cyclin D1+.

T-cells

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

Hodgkin's lymphoma

Classic types:

  • CD30 Reed-Sternberg cells (RSCs) +ve ~98%.[16]
  • CD15 Reed-Sternberg cells +ve ~80%, stains neutrophils.

Germ cell tumours

Seminoma

  • D2-40 +ve.[1]
  • OCT 3/4 +ve.

Embryonal carcinoma

  • CD30 +ve - cytoplasm, cell membrane, Golgi.
    • Rarely positive in seminoma.
  • CK7 +ve.[17]
  • 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.

Sarcomas

MFH panel (MSH):

  • CD34 - GISTs, solitary fibrous tumour/hemangiopericytoma, DFSP, angiosarcoma.
  • S-100 - neural differentiation, melanoma.
  • Desmin - smooth muscle.
  • MIB1 - proliferation marker (target is Ki-67 protein).
  • CD99 - blue small cell tumours, membranous staining EWS.
  • Bcl-2.
  • PGP 9.5.
  • SMMS - smooth muscle.
  • Caldesmon - muscle.
  • PDGFR - GIST.

Muscle markers

  • Desmin - all three types.
  • Caldesmon - smooth muscle.
  • Smooth muscle myosin - smooth muscle.
  • MyoD1 - skeletal muscle.

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.[18]

Carcinomas

CK7 and CK20

CK7+ CK20-

  • Ovary (but not mucinous).
  • Breast.
  • Endometrial.
  • Lung (adenocarcinoma).
  • Mesothelium.
  • Salivary.
  • Thyroid (all).

Mnemonic: OBE + lung x2 + H&N x2

CK7- CK20+

  • Colorectal adenocarcinoma.
  • Merkel cell tumour.

CK7+ CK20+

  • Pancreatic adenocarcinoma.
  • Ovary, mucinous subtype.
  • Occasionally gastric adeno, cholangiocarcinoma.
  • Transistional cell carcinoma or urothelial cell carcinoma (UCC).
  • Esophagus (adenocarcinoma).

Mnemonic: POOTE.

CK7- CK20-

  • Neuroendocrine lung (small cell carcinoma).
  • Adrenocortical carcinoma (ACC).
  • Squamous cell carcinoma (all sites of the body).
  • Hepatocellular carcinoma (HCC).
  • Thymoma.
  • Urogenital tumours - germ cell tumours.
  • Renal cell carcinoma (clear cell type).
  • Prostate adenocarcinoma.

Mnemonic: NASH TURP.

Vimentin & cytokeratin

A few tumours are positive for both vimentin and cytokeratins.

References

  1. ↑ 1.0 1.1 Iczkowski KA, Butler SL, Shanks JH, et al (February 2008). "Trials of new germ cell immunohistochemical stains in 93 extragonadal and metastatic germ cell tumors". Hum. Pathol. 39 (2): 275-81. doi:10.1016/j.humpath.2007.07.002. PMID 18045648.
  2. ↑ http://www.nordiqc.org/Epitopes/Cytokeratins/cytokeratins.htm
  3. ↑ Murata T, Nakashima Y, Takeuchi M, Sueishi K, Inomata H (September 1993). "The diagnostic use of low molecular weight keratin expression in sebaceous carcinoma". Pathol. Res. Pract. 189 (8): 888–93. PMID 7508102.
  4. ↑ Jagirdar J (March 2008). "Application of immunohistochemistry to the diagnosis of primary and metastatic carcinoma to the lung". Arch. Pathol. Lab. Med. 132 (3): 384–96. PMID 18318581. http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0003-9985&volume=132&page=384.
  5. ↑ http://www.antibodies-online.com/antibody/125649/P504S+alphaMethylacylCoA+Racemace+AMACR+Human/
  6. ↑ Anatelli F, Chuang ST, Yang XJ, Wang HL. (2008). "Value of glypican 3 immunostaining in the diagnosis of hepatocellular carcinoma on needle biopsy". Am J Clin Pathol. 130 (2): 219-23?. doi:10.1309/WMB5PX57Y4P8QCTY. PMID 18628090.
  7. ↑ The diagnostic value of hepatocyte paraffin antibody 1 in differentiating hepatocellular neoplasms from nonhepatic tumors: a review. Lamps LW, Folpe AL. Adv Anat Pathol. 2003 Jan;10(1):39-43. Review. PMID 12502967.
  8. ↑ Lei JY, Bourne PA, diSant'Agnese PA, Huang J (April 2006). "Cytoplasmic staining of TTF-1 in the differential diagnosis of hepatocellular carcinoma vs cholangiocarcinoma and metastatic carcinoma of the liver". Am. J. Clin. Pathol. 125 (4): 519–25. doi:10.1309/59TN-EFAL-UL5W-J94M. PMID 16627262.
  9. ↑ Pernick NL, DaSilva M, Gangi MD, Crissman J, Adsay V (November 1999). ""Histiocytic markers" in melanoma". Mod. Pathol. 12 (11): 1072–7. PMID 10574605.
  10. ↑ Goldstein NS, Bassi D (May 2001). "Cytokeratins 7, 17, and 20 reactivity in pancreatic and ampulla of vater adenocarcinomas. Percentage of positivity and distribution is affected by the cut-point threshold". Am. J. Clin. Pathol. 115 (5): 695–702. doi:10.1309/1NCM-46QX-3B5T-7XHR. PMID 11345833.
  11. ↑ Geller SA, Dhall D, Alsabeh R (March 2008). "Application of immunohistochemistry to liver and gastrointestinal neoplasms: liver, stomach, colon, and pancreas". Arch. Pathol. Lab. Med. 132 (3): 490–9. PMID 18318589.
  12. ↑ 12.0 12.1 Alkushi A, Irving J, Hsu F, et al. (March 2003). "Immunoprofile of cervical and endometrial adenocarcinomas using a tissue microarray". Virchows Arch. 442 (3): 271-7. doi:10.1007/s00428-002-0752-4. PMID 12647218.
  13. ↑ URL: http://www.nature.com/modpathol/journal/v19/n8/full/3800620a.html
  14. ↑ LAE 15 Jan 2009.
  15. ↑ [Evaluation of immunohistochemical markers for differential diagnosis of hepatocellular carcinoma from intrahepatic cholangiocarcinoma] Dong H, Cong WL, Zhu ZZ, Wang B, Xian ZH, Yu H. Zhonghua Zhong Liu Za Zhi. 2008 Sep;30(9):702-5. Chinese. PMID 19173916.
  16. ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 567. ISBN 978-0781765275.
  17. ↑ Cheville JC, Rao S, Iczkowski KA, Lohse CM, Pankratz VS (April 2000). "Cytokeratin expression in seminoma of the human testis". Am. J. Clin. Pathol. 113 (4): 583–8. doi:10.1309/3QLC-5MF1-JYXU-A5XX. PMID 10761461.
  18. ↑ http://www.genenames.org/data/hgnc_data.php?hgnc_id=21086
  19. ↑ Llombart-Bosch A, Lopez-Guerrero JA, Peydro-Olaya A (2002). "Synovial sarcoma (SS): new perspectives supported by modern technology". Arkh. Patol. 64 (3): 39–47. PMID 15338724.
  20. ↑ http://cat.inist.fr/?aModele=afficheN&cpsidt=2504165
  21. ↑ http://www.nature.com/modpathol/journal/v14/n9/full/3880401a.html

External links

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