Difference between revisions of "Immunohistochemical staining"
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**OCT4. | **OCT4. | ||
***PLAP ([[placental alkaline phosphatase]]) - not very sensitive.<ref name=pmid18045648>{{cite journal |author=Iczkowski KA, Butler SL, Shanks JH, ''et al'' |title=Trials of new germ cell immunohistochemical stains in 93 extragonadal and metastatic germ cell tumors |journal=Hum. Pathol. |volume=39 |issue=2 |pages=275-81 |year=2008 |month=February |pmid=18045648 |doi=10.1016/j.humpath.2007.07.002 |url=}}</ref> | ***PLAP ([[placental alkaline phosphatase]]) - not very sensitive.<ref name=pmid18045648>{{cite journal |author=Iczkowski KA, Butler SL, Shanks JH, ''et al'' |title=Trials of new germ cell immunohistochemical stains in 93 extragonadal and metastatic germ cell tumors |journal=Hum. Pathol. |volume=39 |issue=2 |pages=275-81 |year=2008 |month=February |pmid=18045648 |doi=10.1016/j.humpath.2007.07.002 |url=}}</ref> | ||
**Glypican 3 +ve. | **[[Glypican 3]] +ve. | ||
*Neuroendocrine carcinoma. | *Neuroendocrine carcinoma. | ||
**Chromogranin A. | **Chromogranin A. | ||
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**[[CD56]]. | **[[CD56]]. | ||
**CD57.<ref name=pmid12727026>{{Cite journal | last1 = Kurokawa | first1 = M. | last2 = Nabeshima | first2 = K. | last3 = Akiyama | first3 = Y. | last4 = Maeda | first4 = S. | last5 = Nishida | first5 = T. | last6 = Nakayama | first6 = F. | last7 = Amano | first7 = M. | last8 = Ogata | first8 = K. | last9 = Setoyama | first9 = M. | title = CD56: a useful marker for diagnosing Merkel cell carcinoma. | journal = J Dermatol Sci | volume = 31 | issue = 3 | pages = 219-24 | month = May | year = 2003 | doi = | PMID = 12727026 }}</ref> | **CD57.<ref name=pmid12727026>{{Cite journal | last1 = Kurokawa | first1 = M. | last2 = Nabeshima | first2 = K. | last3 = Akiyama | first3 = Y. | last4 = Maeda | first4 = S. | last5 = Nishida | first5 = T. | last6 = Nakayama | first6 = F. | last7 = Amano | first7 = M. | last8 = Ogata | first8 = K. | last9 = Setoyama | first9 = M. | title = CD56: a useful marker for diagnosing Merkel cell carcinoma. | journal = J Dermatol Sci | volume = 31 | issue = 3 | pages = 219-24 | month = May | year = 2003 | doi = | PMID = 12727026 }}</ref> | ||
*Melanoma. | *[[Melanoma]]. | ||
**S-100, HMB-45, Melan A (MART-1). | **S-100, HMB-45, Melan A (MART-1). | ||
***Additional: melanoma cocktail (HMB-45, MART-1)<ref name=pmid18360125>{{cite journal |author=Jani P, Chetty R, Ghazarian DM |title=An unusual composite pilomatrix carcinoma with intralesional melanocytes: differential diagnosis, immunohistochemical evaluation, and review of the literature |journal=Am J Dermatopathol |volume=30 |issue=2 |pages=174–7 |year=2008 |month=April |pmid=18360125 |doi=10.1097/DAD.0b013e318165b8fe |url=}}</ref>, microphthalmia,<ref>URL: [http://www.ncbi.nlm.nih.gov/omim/156845 http://www.ncbi.nlm.nih.gov/omim/156845]. Accessed on: 18 August 2010.</ref> tyrosinase.<ref name=pmid17227112>{{Cite journal | last1 = Roma | first1 = AA. | last2 = Magi-Galluzzi | first2 = C. | last3 = Zhou | first3 = M. | title = Differential expression of melanocytic markers in myoid, lipomatous, and vascular components of renal angiomyolipomas. | journal = Arch Pathol Lab Med | volume = 131 | issue = 1 | pages = 122-5 | month = Jan | year = 2007 | doi = 10.1043/1543-2165(2007)131[122:DEOMMI]2.0.CO;2 | PMID = 17227112 }}</ref> | ***Additional: melanoma cocktail (HMB-45, MART-1)<ref name=pmid18360125>{{cite journal |author=Jani P, Chetty R, Ghazarian DM |title=An unusual composite pilomatrix carcinoma with intralesional melanocytes: differential diagnosis, immunohistochemical evaluation, and review of the literature |journal=Am J Dermatopathol |volume=30 |issue=2 |pages=174–7 |year=2008 |month=April |pmid=18360125 |doi=10.1097/DAD.0b013e318165b8fe |url=}}</ref>, microphthalmia,<ref>URL: [http://www.ncbi.nlm.nih.gov/omim/156845 http://www.ncbi.nlm.nih.gov/omim/156845]. Accessed on: 18 August 2010.</ref> tyrosinase.<ref name=pmid17227112>{{Cite journal | last1 = Roma | first1 = AA. | last2 = Magi-Galluzzi | first2 = C. | last3 = Zhou | first3 = M. | title = Differential expression of melanocytic markers in myoid, lipomatous, and vascular components of renal angiomyolipomas. | journal = Arch Pathol Lab Med | volume = 131 | issue = 1 | pages = 122-5 | month = Jan | year = 2007 | doi = 10.1043/1543-2165(2007)131[122:DEOMMI]2.0.CO;2 | PMID = 17227112 }}</ref> | ||
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===Prostate gland=== | ===Prostate gland=== | ||
*PSA - [[prostate gland|prostatic]]-specific antigen. | *[[PSA]] - [[prostate gland|prostatic]]-specific antigen. | ||
*PSAP - prostatic-specific acid phosphatase. | *PSAP - prostatic-specific acid phosphatase. | ||
**May be positive in hindgut [[neuroendocrine tumour]]s.<ref name=pmid>{{Cite journal | last1 = Azumi | first1 = N. | last2 = Traweek | first2 = ST. | last3 = Battifora | first3 = H. | title = Prostatic acid phosphatase in carcinoid tumors. Immunohistochemical and immunoblot studies. | journal = Am J Surg Pathol | volume = 15 | issue = 8 | pages = 785-90 | month = Aug | year = 1991 | doi = | PMID = 1712549 }}</ref> | **May be positive in hindgut [[neuroendocrine tumour]]s.<ref name=pmid>{{Cite journal | last1 = Azumi | first1 = N. | last2 = Traweek | first2 = ST. | last3 = Battifora | first3 = H. | title = Prostatic acid phosphatase in carcinoid tumors. Immunohistochemical and immunoblot studies. | journal = Am J Surg Pathol | volume = 15 | issue = 8 | pages = 785-90 | month = Aug | year = 1991 | doi = | PMID = 1712549 }}</ref> | ||
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===[[Colorectal tumours|Colorectal carcinoma]] markers=== | ===[[Colorectal tumours|Colorectal carcinoma]] markers=== | ||
*CK20. | *[[CK20]]. | ||
*CDX2. | *CDX2. | ||
**Uncommon in primary lung, breast, pancreas, kidney, gallbladder, liver, urinary bladder, thyroid gland.<ref name=pmid15205684 >{{Cite journal | last1 = Kaimaktchiev | first1 = V. | last2 = Terracciano | first2 = L. | last3 = Tornillo | first3 = L. | last4 = Spichtin | first4 = H. | last5 = Stoios | first5 = D. | last6 = Bundi | first6 = M. | last7 = Korcheva | first7 = V. | last8 = Mirlacher | first8 = M. | last9 = Loda | first9 = M. | title = The homeobox intestinal differentiation factor CDX2 is selectively expressed in gastrointestinal adenocarcinomas. | journal = Mod Pathol | volume = 17 | issue = 11 | pages = 1392-9 | month = Nov | year = 2004 | doi = 10.1038/modpathol.3800205 | PMID = 15205684 }}</ref> | **Uncommon in primary lung, breast, pancreas, kidney, gallbladder, liver, urinary bladder, thyroid gland.<ref name=pmid15205684 >{{Cite journal | last1 = Kaimaktchiev | first1 = V. | last2 = Terracciano | first2 = L. | last3 = Tornillo | first3 = L. | last4 = Spichtin | first4 = H. | last5 = Stoios | first5 = D. | last6 = Bundi | first6 = M. | last7 = Korcheva | first7 = V. | last8 = Mirlacher | first8 = M. | last9 = Loda | first9 = M. | title = The homeobox intestinal differentiation factor CDX2 is selectively expressed in gastrointestinal adenocarcinomas. | journal = Mod Pathol | volume = 17 | issue = 11 | pages = 1392-9 | month = Nov | year = 2004 | doi = 10.1038/modpathol.3800205 | PMID = 15205684 }}</ref> | ||
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===[[Kidney tumours|Kidney]]=== | ===[[Kidney tumours|Kidney]]=== | ||
[[Renal cell carcinoma]]: | [[Renal cell carcinoma]]: | ||
*RCC, EMA, CD10. | *RCC, [[EMA]], CD10. | ||
*CK7 -ve in clear cell RCC. | *[[CK7]] -ve in clear cell RCC. | ||
*[[AMACR]] +ve in papillary RCC. | *[[AMACR]] +ve in papillary RCC. | ||
*D2-40 +ve in ChRCC. | *D2-40 +ve in ChRCC. | ||
Line 196: | Line 196: | ||
Specific entities: | Specific entities: | ||
*[[EMA]] +ve: [[meningioma]], [[ependymoma]] (cytoplasm dot-like).<ref name=Ref_PSNP12>{{Ref PSNP|12}}</ref> | *[[EMA]] +ve: [[meningioma]], [[ependymoma]] (cytoplasm dot-like).<ref name=Ref_PSNP12>{{Ref PSNP|12}}</ref> | ||
*[[ATRX]] -ve: [[astrocytoma]] | *[[ATRX]] -ve: [[astrocytoma]]. | ||
*[[INI1]] -ve: [[AT/RT]] | *[[INI1]] -ve: [[AT/RT]]. | ||
Tumour (low-grade gliomas): | Tumour (low-grade gliomas): | ||
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===Prostate versus bladder=== | ===Prostate versus bladder=== | ||
Prostate adenocarcinoma vs. urothelial carcinoma: | Prostate adenocarcinoma vs. urothelial carcinoma: | ||
*Prostate adenocarcinoma: PSA +ve, PSAP +ve, AR +ve, CK7 -ve, CK20 -ve. | *Prostate adenocarcinoma: PSA +ve, PSAP +ve, AR +ve, CK7 -ve, CK20 -ve, GATA3 -ve. | ||
*Urothelial carcinoma: CK7 +ve, CK20 +ve, PSA -ve, PSAP -ve, AR -ve. | *Urothelial carcinoma: [[GATA3]] +ve, CK7 +ve, CK20 +ve, PSA -ve, PSAP -ve, AR -ve. | ||
===Breast versus ovary=== | ===Breast versus ovary=== |
Revision as of 00:59, 30 September 2015
Immunohistochemical staining, also immunostaining, is a powerful tool. It is abbreviated IHC.
Utility
Use of immunohistochemistry:[1]
- Unknown primary tumours.
- Poorly differentiated tumours.
- Prognostic markers, e.g. ERBB2 (HER2).
- Proving clonality - in the context of hematologic malignancies.
Theory
- Antigen retrieval.
- Antibody binds to the antigen.
- Amplification - needed as the signal is usually too weak.
Signaling systems
- Avidin-biotin complex.
- Polymer based methods.
- Newer.
Quality control
This is an evolving area in pathology that has been ignored for a surprisingly long time.
It is touched upon the in the quality article in the immunohistochemistry section.
Interpretation
To determine whether a stain is (1) done correctly, and (2) positive, one needs to know:
- What tissues it stains:
- Tumour.
- Normal tissue.
- How it stains the various tissues:
- Patchy.
- Diffuse.
- Where it stains the various tissues:
- Nucleus.
- Cytoplasm.
- Membrane.
- A combination of the above.
Generally, interpretations can be subjective, and this is especially true when the staining is weak and focal. In other words, "... your weak [positive] stain might be somebody else’s negative."[4] This is often reflected in publications reporting contradictory results regarding the rates of positivity for stains in different tumours, even if the methods uses are identical.
The cynical might say it is unwritten rule that: "... if the stain is weak and focal it can be anything you want to make it -- positive or negative -- so it fits perfectly with your diagnosis!"
In cases where the morphology is unclear, it is judicious to have two or more immunostains that support the diagnosis, and negative stains for important entities in the differential diagnosis.
One third pathologists substantially overestimate and one third underestimate the diagnostic significance of unexpected immunohistochemical staining results.[5]
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.
- Vimentin.
- Germ cell tumours.
- OCT4.
- PLAP (placental alkaline phosphatase) - not very sensitive.[6]
- Glypican 3 +ve.
- OCT4.
- Neuroendocrine carcinoma.
- Melanoma.
- Hematologic.
- Lymphoma/leukemia.
- CD45 (common leukocyte antigen).
- CD30.
- Plasma cell:
- Kappa.
- Lambda.
- CD138.
- Lymphoma/leukemia.
Keratins
Classification:[11]
- Low molecular weight keratins (LMWK): 7, 8/18, 19, 20.
- High molecular weight keratins (HWMK): 4, 10, 13, 14, 17.
Uses:
- CK8 (CAM5.2)[12] - used to look for mets from breast cancer in axillary lymph nodes.
- HWMK (e.g. K903[13]) - squamous cell carcinoma.
Organ specific
Thyroid and lung
- TTF-1 (thyroid transcription factor-1) -- +ve in thyroid gland malignancies.
- Thyroglobulin usu. +ve in the thyroid.[15]
- Negative in classic medullary thyroid carcinoma.[16]
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.
- HER2/neu+ cancers Tx'ed with trastuzumab (Herceptin).
Prostate gland
- PSA - prostatic-specific antigen.
- PSAP - prostatic-specific acid phosphatase.
- May be positive in hindgut neuroendocrine tumours.[17]
- p63 - stains nuclei of basal cell in normal prostate.
- 34betaE12 - stains basal cells in normal prostate.
- AMACR (racemase, P504S[18]) - present in adenocarcinoma (NOT in normal prostate).
- AR - usually present in prostate confined cancers.[19]
- CAP cocktail - AKA CAP, AKA PIN-4, AKA PIN.
- Consists of: AMACR, p63 and HMWK.
- Image: CAP cocktail (webpathology.com).
Colorectal carcinoma markers
- CK20.
- CDX2.
- Uncommon in primary lung, breast, pancreas, kidney, gallbladder, liver, urinary bladder, thyroid gland.[20]
- CEA.
Small bowel
- CDX2.
- Villin.
Kidney
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.
- Hepatocellular carcinoma (HCC) stains with glypican 3, while liver with dysplastic changes and/or cirrhotic changes does not.[21]
- HepPar-1 (hepatocytes paraffin antibody 1) - labels hepatocellular mitochondria.[22]
HCC vs. cholangiocarcinoma:
- TTF-1: ~90-100% +ve (cytoplasmic) in HCC vs. ~10% in cholangiocarcinoma.[23]
Mesothelium
Panel:[24]
- Mesothelial markers:
- Calretinin.
- WT-1.
- D2-40.
- CK5/6.
- Carcinoma markers:
- CEA (monoclonal and polyclonal).
- TTF-1.
- Ber-EP4.
- MOC-31.
Note:
- One should use two mesothelial markers and two carcinoma markers.[24]
Pancreas
- CK17 - approx. 50% of pancreaticobiliary adenocarcinomas & patchy.[25]
- CK19.[26]
Neuropathology
General:
- S-100.
Glial:
- GFAP.
Neuronal:
- Synaptophysin.
- Chromogranin.
Glial/Neuronal:
- MAP2
- CD56
Specific entities:
- EMA +ve: meningioma, ependymoma (cytoplasm dot-like).[27]
- ATRX -ve: astrocytoma.
- INI1 -ve: AT/RT.
Tumour (low-grade gliomas):
- IDH-1 +ve.
- Usually negative in glioblastoma.
Miscellaneous
Macrophages
- CD68.
Special:
- S100 -- +ve in Rosai-Dorfman disease.
- CD1a -- +ve in Langerhans cell histiocytosis, Langerhans histocytes.
Special, less common:
One organ versus another
Cervix versus uterus
- Cervix (typically): CEA +ve,[33] p16 +ve.
- ... and ER -ve, PR -ve, vimentin -ve.
- Uterus (typically): vimentin +ve, ER +ve, PR +ve.[34]
- ... and CEA -ve, p16 -ve.
Liver versus bile duct
Intrahepatic cholangiocarcinoma (ICC) vs. hepatocellular carcinoma (HCC):[35]
Prostate versus bladder
Prostate adenocarcinoma vs. urothelial carcinoma:
- Prostate adenocarcinoma: PSA +ve, PSAP +ve, AR +ve, CK7 -ve, CK20 -ve, GATA3 -ve.
- Urothelial carcinoma: GATA3 +ve, CK7 +ve, CK20 +ve, PSA -ve, PSAP -ve, AR -ve.
Breast versus ovary
Breast carcinoma versus ovarian carcinoma:
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%.[39]
- CD15 Reed-Sternberg cells +ve ~80%, stains neutrophils.
Germ cell tumours
Seminoma
- D2-40 +ve.[6]
- OCT 3/4 +ve.
Embryonal carcinoma
- CD30 +ve - cytoplasm, cell membrane, Golgi.
- Rarely positive in seminoma.
- CK7 +ve.[40]
- 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:
- CD34 - GIST, angiosarcoma, Kaposi sarcoma, solitary fibrous tumour/hemangiopericytoma, dermatofibrosarcoma protuberans (DFSP), spindle cell lipoma.
- S-100 - neural differentiation, melanoma.
- Desmin - smooth muscle.
- MIB1 - proliferation marker (target is Ki-67 protein).
- CD99 - blue small cell tumours, membranous staining EWS.
- BCL2 - synovial sarcoma, small cell lymphomas, spindle cell lipoma.[41][42]
- PGP 9.5.
- SMMS - smooth muscle.
- Caldesmon - muscle.
- PDGFR - GIST.
- STAT6 - Hemangiopericytoma/SFT.
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).
Notes:
- Ki-67 is found in lymphocytes - these are a positive control; lymphocytes should not be confused for (positive) tumour cells.[43]
- MIB1 should not be confused with mindbomb homolog 1 (MIB-1), a gene that regulates apoptosis.[44]
Carcinomas
CK7 and CK20
CK7+ CK20-
- Ovary (but not mucinous).
- Breast.
- Endometrial.
- Lung (adenocarcinoma).
- Mesothelioma.
- Salivary gland.
- Thyroid gland (all).
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).§
- Esophageal adenocarcinoma.
Mnemonic: POOTE.
Note:
- § - Transitional cell carcinoma of the ovary is usu. CK20 -ve.[45]
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 and cytokeratin positivity
A few tumours are positive for both vimentin and cytokeratins.
Common tumours:
- Renal cell carcinoma.[46]
- Endometrial carcinoma.[33]
- Ovarian serous carcinoma.[46]
- Papillary thyroid carcinoma.[46]
- Sarcomatoid carcinoma (spindle cell carcinoma).[46]
Rare tumours:
- Synovial sarcoma.[47]
- Rhabdoid tumour.[48]
- Epithelioid sarcoma.[49]
- Epithelioid angiosarcoma.[46]
- Desmoplastic small round cell tumour.[46]
- Anaplastic thyroid carcinoma.[46]
- Biphasic malignant mesothelioma.[46]
- Carcinosarcoma.[46]
Common tumours that uncommonly have the pattern:
Sarcomas cytokeratins
Most sarcomas are cytokeratin negative.
Exceptions - classic:
- Angiosarcoma, epithelioid.
- Synovial sarcoma.
- Chordoma.
- Desmoplastic small round cell tumour.
- Epithelioid sarcoma.
Others:
See also
References
- ↑ Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 175. ISBN 978-1416054542.
- ↑ Vosse, BA.; Seelentag, W.; Bachmann, A.; Bosman, FT.; Yan, P. (Mar 2007). "Background staining of visualization systems in immunohistochemistry: comparison of the Avidin-Biotin Complex system and the EnVision+ system.". Appl Immunohistochem Mol Morphol 15 (1): 103-7. PMID 17536316.
- ↑ Vosse, BA.; Seelentag, W.; Bachmann, A.; Bosman, FT.; Yan, P. (Mar 2007). "Background staining of visualization systems in immunohistochemistry: comparison of the Avidin-Biotin Complex system and the EnVision+ system.". Appl Immunohistochem Mol Morphol 15 (1): 103-7. PMID 17536316.
- ↑ URL: http://bitesizebio.com/articles/immunohistochemistry-getting-the-stain-you-want/. Accessed on: 1 September 2012.
- ↑ Galloway, M. (2011). "Base-rate error in the interpretation of immunohistochemistry.". Patholog Res Int 2011: 636495. doi:10.4061/2011/636495. PMID 21660231.
- ↑ 6.0 6.1 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.
- ↑ Kurokawa, M.; Nabeshima, K.; Akiyama, Y.; Maeda, S.; Nishida, T.; Nakayama, F.; Amano, M.; Ogata, K. et al. (May 2003). "CD56: a useful marker for diagnosing Merkel cell carcinoma.". J Dermatol Sci 31 (3): 219-24. PMID 12727026.
- ↑ Jani P, Chetty R, Ghazarian DM (April 2008). "An unusual composite pilomatrix carcinoma with intralesional melanocytes: differential diagnosis, immunohistochemical evaluation, and review of the literature". Am J Dermatopathol 30 (2): 174–7. doi:10.1097/DAD.0b013e318165b8fe. PMID 18360125.
- ↑ URL: http://www.ncbi.nlm.nih.gov/omim/156845. Accessed on: 18 August 2010.
- ↑ Roma, AA.; Magi-Galluzzi, C.; Zhou, M. (Jan 2007). "Differential expression of melanocytic markers in myoid, lipomatous, and vascular components of renal angiomyolipomas.". Arch Pathol Lab Med 131 (1): 122-5. doi:10.1043/1543-2165(2007)131[122:DEOMMI]2.0.CO;2. PMID 17227112.
- ↑ http://www.nordiqc.org/Epitopes/Cytokeratins/cytokeratins.htm
- ↑ 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.
- ↑ URL: http://www.aruplab.com/guides/ug/tests/2003978.jsp. Accessed on: 17 March 2011.
- ↑ 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.
- ↑ Dralle, H.; Böcker, W. (1982). "[Thyroglobulin immunohistochemistry: new aspects of pathophysiology and differential diagnosis of benign and malignant goitre (author's transl)].". Langenbecks Arch Chir 356 (3): 205-12. PMID 7070163.
- ↑ de Micco, C.; Chapel, F.; Dor, AM.; Garcia, S.; Ruf, J.; Carayon, P.; Henry, JF.; Lebreuil, G. (Mar 1993). "Thyroglobulin in medullary thyroid carcinoma: immunohistochemical study with polyclonal and monoclonal antibodies.". Hum Pathol 24 (3): 256-62. PMID 8454270.
- ↑ Azumi, N.; Traweek, ST.; Battifora, H. (Aug 1991). "Prostatic acid phosphatase in carcinoid tumors. Immunohistochemical and immunoblot studies.". Am J Surg Pathol 15 (8): 785-90. PMID 1712549.
- ↑ http://www.antibodies-online.com/antibody/125649/P504S+alphaMethylacylCoA+Racemace+AMACR+Human/
- ↑ Fleischmann, A.; Rocha, C.; Schobinger, S.; Seiler, R.; Wiese, B.; Thalmann, GN. (Apr 2011). "Androgen receptors are differentially expressed in Gleason patterns of prostate cancer and down-regulated in matched lymph node metastases.". Prostate 71 (5): 453-60. doi:10.1002/pros.21259. PMID 20878946.
- ↑ Kaimaktchiev, V.; Terracciano, L.; Tornillo, L.; Spichtin, H.; Stoios, D.; Bundi, M.; Korcheva, V.; Mirlacher, M. et al. (Nov 2004). "The homeobox intestinal differentiation factor CDX2 is selectively expressed in gastrointestinal adenocarcinomas.". Mod Pathol 17 (11): 1392-9. doi:10.1038/modpathol.3800205. PMID 15205684.
- ↑ 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.
- ↑ 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.
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