Difference between revisions of "Immunohistochemical staining"

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Immunohistochemical staining (view source)

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#Prognostic markers, e.g. ERBB2 (HER2).
#Prognostic markers, e.g. ERBB2 (HER2).
#Proving clonality - in the context of hematologic malignancies.
#Proving clonality - in the context of hematologic malignancies.
#Mutation specific antibodies, eg. [[IDH-1]] R132H.
Method was introduced in 1941 by Coons.<ref>{{Cite journal  | last1 = Coons | first1 = AH. | title = The development of immunohistochemistry. | journal = Ann N Y Acad Sci | volume = 177 | issue =  | pages = 5-9 | month = Jun | year = 1971 | doi =  | PMID = 4400556 }}</ref>


==Theory==
==Theory==
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**Older.<ref>{{Cite journal  | last1 = Vosse | first1 = BA. | last2 = Seelentag | first2 = W. | last3 = Bachmann | first3 = A. | last4 = Bosman | first4 = FT. | last5 = Yan | first5 = P. | title = Background staining of visualization systems in immunohistochemistry: comparison of the Avidin-Biotin Complex system and the EnVision+ system. | journal = Appl Immunohistochem Mol Morphol | volume = 15 | issue = 1 | pages = 103-7 | month = Mar | year = 2007 | doi =  | PMID = 17536316 }}</ref>
**Older.<ref>{{Cite journal  | last1 = Vosse | first1 = BA. | last2 = Seelentag | first2 = W. | last3 = Bachmann | first3 = A. | last4 = Bosman | first4 = FT. | last5 = Yan | first5 = P. | title = Background staining of visualization systems in immunohistochemistry: comparison of the Avidin-Biotin Complex system and the EnVision+ system. | journal = Appl Immunohistochem Mol Morphol | volume = 15 | issue = 1 | pages = 103-7 | month = Mar | year = 2007 | doi =  | PMID = 17536316 }}</ref>
**May suffer from endogenous avidin-biotin activity.<ref name=pmid17536316>{{Cite journal  | last1 = Vosse | first1 = BA. | last2 = Seelentag | first2 = W. | last3 = Bachmann | first3 = A. | last4 = Bosman | first4 = FT. | last5 = Yan | first5 = P. | title = Background staining of visualization systems in immunohistochemistry: comparison of the Avidin-Biotin Complex system and the EnVision+ system. | journal = Appl Immunohistochem Mol Morphol | volume = 15 | issue = 1 | pages = 103-7 | month = Mar | year = 2007 | doi =  | PMID = 17536316 }}</ref>
**May suffer from endogenous avidin-biotin activity.<ref name=pmid17536316>{{Cite journal  | last1 = Vosse | first1 = BA. | last2 = Seelentag | first2 = W. | last3 = Bachmann | first3 = A. | last4 = Bosman | first4 = FT. | last5 = Yan | first5 = P. | title = Background staining of visualization systems in immunohistochemistry: comparison of the Avidin-Biotin Complex system and the EnVision+ system. | journal = Appl Immunohistochem Mol Morphol | volume = 15 | issue = 1 | pages = 103-7 | month = Mar | year = 2007 | doi =  | PMID = 17536316 }}</ref>
***Higher false positive rates than with polymer based methods.
*Polymer based methods.
*Polymer based methods.
**Newer.
**Newer.
**Less prone to false positives.
***Negative controls not needed or infrequently required.<ref name=pmid24714041>{{Cite journal  | last1 = Torlakovic | first1 = EE. | last2 = Francis | first2 = G. | last3 = Garratt | first3 = J. | last4 = Gilks | first4 = B. | last5 = Hyjek | first5 = E. | last6 = Ibrahim | first6 = M. | last7 = Miller | first7 = R. | last8 = Nielsen | first8 = S. | last9 = Petcu | first9 = EB. | title = Standardization of negative controls in diagnostic immunohistochemistry: recommendations from the international ad hoc expert panel. | journal = Appl Immunohistochem Mol Morphol | volume = 22 | issue = 4 | pages = 241-52 | month = Apr | year = 2014 | doi = 10.1097/PAI.0000000000000069 | PMID = 24714041 }}</ref>
===Signal assessment===
*Manual (Morphology) vs. automated (Speed) counting.
*Choice of proper chromogen.
**Dynamic range of DAB is 1-2logs vs. fluorescent probes 2-3logs.
**Protein expression range can be up to 4 logs in gene amplification (information is missed in IHC).
**FastRed stains are more suited in melanocytic tumors than DAB.
*Use of established cutoffs for "intensity" and for "positive" staining.
*Visual pattern recogniton vs. detecting spatial subtle changes.
*Detecting differences at low intensity with human eye is less accurate.


==Quality control==
==Quality control==
This is an evolving area in pathology that has been ignored for a surprisingly long time.   
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 ''[[Quality#Immunohistochemistry|immunohistochemistry]]'' section.   
It is touched upon the in the ''[[quality]]'' article in the ''[[Quality#Immunohistochemistry|immunohistochemistry]]'' section.
 
There are at least 62 pre-analytical variables to be considered, that may affect staining results.<ref>{{Cite journal | last1 = Engel | first1 = KB. | last2 = Moore | first2 = HM. | title = Effects of preanalytical variables on the detection of proteins by immunohistochemistry in formalin-fixed, paraffin-embedded tissue. | journal = Arch Pathol Lab Med | volume = 135 | issue = 5 | pages = 537-43 | month = May | year = 2011 | doi = 10.1043/2010-0702-RAIR.1 | PMID = 21526952 }}</ref>


==Interpretation==
==Interpretation==
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#*A combination of the above.
#*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."<ref>URL: [http://bitesizebio.com/articles/immunohistochemistry-getting-the-stain-you-want/ http://bitesizebio.com/articles/immunohistochemistry-getting-the-stain-you-want/]. Accessed on: 1 September 2012.</ref>
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."<ref>URL: [http://bitesizebio.com/articles/immunohistochemistry-getting-the-stain-you-want/ http://bitesizebio.com/articles/immunohistochemistry-getting-the-stain-you-want/]. Accessed on: 1 September 2012.</ref>  


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!"
The cynical might say it is an 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.
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.
Publications with contradicting results are not uncommon. Differences can arise from the fixation, processing protocol, antibody clone and interpretation.
According to Galloway, one third pathologists substantially overestimate the diagnostic significance of unexpected immunohistochemical staining results.<ref name=pmid21660231>{{Cite journal  | last1 = Galloway | first1 = M. | title = Base-rate error in the interpretation of immunohistochemistry. | journal = Patholog Res Int | volume = 2011 | issue =  | pages = 636495 | month =  | year = 2011 | doi = 10.4061/2011/636495 | PMID = 21660231 }}</ref>


==General (malignant) differential diagnosis==
==General (malignant) differential diagnosis==
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*Carcinoma.
*Carcinoma.
**AE1/AE3 - pankeratin.
**[[AE1/AE3]] - pankeratin.
**Others: [[EMA]], HMWK, LMWK.
**Others: [[EMA]], HMWK, LMWK.
*Sarcoma.
*Sarcoma.
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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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==Keratins==
==Keratins==
Classification:<ref>[http://www.nordiqc.org/Epitopes/Cytokeratins/cytokeratins.htm http://www.nordiqc.org/Epitopes/Cytokeratins/cytokeratins.htm]</ref>
{{Main|Keratins}}
*Low molecular weight keratins (LMWK): 7, 8/18, 19, 20.
Mark epithelial cells. Are typically seen in [[carcinoma]]s.
*High molecular weight keratins (HWMK): 4, 10, 13, 14, 17.
 
Uses:
*CK8 (CAM5.2)<ref>{{cite journal |author=Murata T, Nakashima Y, Takeuchi M, Sueishi K, Inomata H |title=The diagnostic use of low molecular weight keratin expression in sebaceous carcinoma |journal=Pathol. Res. Pract. |volume=189 |issue=8 |pages=888–93 |year=1993 |month=September |pmid=7508102 |doi= |url=}}</ref> - used to look for mets from breast cancer in axillary lymph nodes.
*HWMK (e.g. K903<ref>URL: [http://www.aruplab.com/guides/ug/tests/2003978.jsp http://www.aruplab.com/guides/ug/tests/2003978.jsp]. Accessed on: 17 March 2011.</ref>) - [[squamous cell carcinoma]].


==Organ specific==
==Organ specific==
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===Breast markers===
===Breast markers===
*[[GCDFP-15]] ([[AKA]] BRST-2) -- specific, but NOT sensitive.
*[[GCDFP-15]] ([[AKA]] BRST-2) -- specific, but NOT sensitive.
*ER (estrogen receptor) - in normal [[breast]].
*[[Estrogen receptor|ER]] (estrogen receptor) - in normal [[breast]].
*PR (progesterone receptor) - in normal breast.
*PR (progesterone receptor) - in normal breast.
*HER2/neu - pathological, assoc. with worse prognosis.
*HER2/neu - pathological, assoc. with worse prognosis.
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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=pmid1712549>{{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>
*p63 - stains nuclei of basal cell in normal [[prostate]].
*[[p63]] - stains nuclei of basal cell in normal [[prostate]].
*34betaE12 - stains basal cells in normal prostate.
*34betaE12 - stains basal 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).
*AR - usually present in prostate confined cancers.<ref name=pmid20878946>{{Cite journal  | last1 = Fleischmann | first1 = A. | last2 = Rocha | first2 = C. | last3 = Schobinger | first3 = S. | last4 = Seiler | first4 = R. | last5 = Wiese | first5 = B. | last6 = Thalmann | first6 = GN. | title = Androgen receptors are differentially expressed in Gleason patterns of prostate cancer and down-regulated in matched lymph node metastases. | journal = Prostate | volume = 71 | issue = 5 | pages = 453-60 | month = Apr | year = 2011 | doi = 10.1002/pros.21259 | PMID = 20878946 }}</ref>
*[[Androgen receptor|AR]] - usually present in prostate confined cancers.<ref name=pmid20878946>{{Cite journal  | last1 = Fleischmann | first1 = A. | last2 = Rocha | first2 = C. | last3 = Schobinger | first3 = S. | last4 = Seiler | first4 = R. | last5 = Wiese | first5 = B. | last6 = Thalmann | first6 = GN. | title = Androgen receptors are differentially expressed in Gleason patterns of prostate cancer and down-regulated in matched lymph node metastases. | journal = Prostate | volume = 71 | issue = 5 | pages = 453-60 | month = Apr | year = 2011 | doi = 10.1002/pros.21259 | PMID = 20878946 }}</ref>
*CAP cocktail - [[AKA]] ''CAP'', [[AKA]] ''PIN-4'', [[AKA]] ''PIN''.
*CAP cocktail - [[AKA]] ''CAP'', [[AKA]] ''PIN-4'', [[AKA]] ''PIN''.
**Consists of: AMACR, p63 and HMWK.
**Consists of: AMACR, [[p63]] and HMWK.
**Image: [http://www.webpathology.com/image.asp?case=96&n=5 CAP cocktail (webpathology.com)].
**Image: [http://www.webpathology.com/image.asp?case=96&n=5 CAP cocktail (webpathology.com)].


===[[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>
*CEA.
*[[CEA]].


===[[Small bowel]]===
===[[Small bowel]]===
*CDX2.
*[[CDX2]].
*Villin.
*[[Villin]].


===[[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.
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===[[Ovarian tumours|Ovary]]===
===[[Ovarian tumours|Ovary]]===
*CA125, CK7+, CK20-.
*[[CA125]], [[CK7]]+, CK20-.
*WT1 -- 90% in serous +ve.
*WT1 -- 90% in serous +ve.


====Serous markers====
====Serous markers====
*WT-1, CA-125, D2-40.
*[[WT-1]], [[CA125]], D2-40.


===[[Liver neoplasms|Liver]]===
===[[Liver neoplasms|Liver]]===
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*Glypican-3.
*Glypican-3.
**[[Hepatocellular carcinoma]] (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>
**[[Hepatocellular carcinoma]] (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>


[[HCC]] vs. [[cholangiocarcinoma]]:
[[HCC]] vs. [[cholangiocarcinoma]]:
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*Mesothelial markers:
*Mesothelial markers:
**Calretinin.
**Calretinin.
**WT-1.
**[[WT-1]].
**D2-40.
**D2-40.
**CK5/6.
**[[CK5/6]].
*Carcinoma markers:
*Carcinoma markers:
**CEA (monoclonal and polyclonal).
**CEA (monoclonal and polyclonal).
**TTF-1.
**[[TTF-1]].
**Ber-EP4.
**[[Ber-EP4]].
**MOC-31.
**MOC-31.


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Glial/Neuronal:
Glial/Neuronal:
*MAP2
*[[MAP2]]
*CD56
*[[CD56]]


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]].


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===
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===[[Seminoma]]===
===[[Seminoma]]===
*D2-40 +ve.<ref name=pmid18045648/>
*D2-40 +ve.<ref name=pmid18045648/>
*OCT 3/4 +ve.
*OCT4 +ve.


===[[Embryonal carcinoma]]===
===[[Embryonal carcinoma]]===
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*S-100 - neural differentiation, melanoma.
*S-100 - neural differentiation, melanoma.
*Desmin - smooth muscle.
*Desmin - smooth muscle.
*MIB1 - proliferation marker (target is Ki-67 protein).
*[[MIB1]] - proliferation marker (target is [[Ki-67]] protein).
*CD99 - blue small cell tumours, membranous staining [[EWS]].
*CD99 - blue small cell tumours, membranous staining [[EWS]].
*BCL2 - [[synovial sarcoma]], [[small cell lymphomas]], spindle cell lipoma.<ref name=Ref_DCHH107>{{Ref DCHH|107}}</ref><ref>URL: [http://ajp.amjpathol.org/cgi/content/full/160/3/759 http://ajp.amjpathol.org/cgi/content/full/160/3/759]. Accessed on: 3 August 2010.</ref>
*BCL2 - [[synovial sarcoma]], [[small cell lymphomas]], spindle cell lipoma.<ref name=Ref_DCHH107>{{Ref DCHH|107}}</ref><ref>URL: [http://ajp.amjpathol.org/cgi/content/full/160/3/759 http://ajp.amjpathol.org/cgi/content/full/160/3/759]. Accessed on: 3 August 2010.</ref>
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*Caldesmon - muscle.
*Caldesmon - muscle.
*PDGFR - GIST.
*PDGFR - GIST.
*[[STAT6]] - [[Hemangiopericytoma]]/SFT.


==Muscle markers==
==Muscle markers==
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==Vimentin and cytokeratin positivity==
==Vimentin and cytokeratin positivity==
{{Main|Vimentin#Vimentin_and_cytokeratin_positivity}}
A few tumours are positive for both vimentin and cytokeratins.
A few tumours are positive for both vimentin and cytokeratins.


Common tumours:
==Sarcomas and cytokeratins==
*[[Renal cell carcinoma]].<ref name=pmid18318577/>
{{Main|Keratins}}
*[[Endometrial carcinoma]].<ref name=pmid12647218/>
*[[Ovarian serous carcinoma]].<ref name=pmid18318577>{{Cite journal  | last1 = Bahrami | first1 = A. | last2 = Truong | first2 = LD. | last3 = Ro | first3 = JY. | title = Undifferentiated tumor: true identity by immunohistochemistry. | journal = Arch Pathol Lab Med | volume = 132 | issue = 3 | pages = 326-48 | month = Mar | year = 2008 | doi = 10.1043/1543-2165(2008)132[326:UTTIBI]2.0.CO;2 | PMID = 18318577 }}</ref>
*[[Papillary thyroid carcinoma]].<ref name=pmid18318577/>
*[[Sarcomatoid carcinoma]] (spindle cell carcinoma).<ref name=pmid18318577/>
 
Rare tumours:
*[[Synovial sarcoma]].<ref name=pmid15338724>{{cite journal |author=Llombart-Bosch A, Lopez-Guerrero JA, Peydro-Olaya A |title=Synovial sarcoma (SS): new perspectives supported by modern technology |journal=Arkh. Patol. |volume=64 |issue=3 |pages=39–47 |year=2002 |pmid=15338724 |doi= |url=}}</ref>
*[[Rhabdoid tumour]].<ref name=pmid11557780>{{cite journal |author=Itakura E, Tamiya S, Morita K, ''et al.'' |title=Subcellular distribution of cytokeratin and vimentin in malignant rhabdoid tumor: three-dimensional imaging with confocal laser scanning microscopy and double immunofluorescence |journal=Mod. Pathol. |volume=14 |issue=9 |pages=854–61 |year=2001 |month=September |pmid=11557780 |doi=10.1038/modpathol.3880401 |url=http://www.nature.com/modpathol/journal/v14/n9/full/3880401a.html}}</ref>
*[[Epithelioid sarcoma]].<ref name=pmid10452506>{{cite journal |author=Miettinen M, Fanburg-Smith JC, Virolainen M, Shmookler BM, Fetsch JF |title=Epithelioid sarcoma: an immunohistochemical analysis of 112 classical and variant cases and a discussion of the differential diagnosis |journal=Hum. Pathol. |volume=30 |issue=8 |pages=934–42 |year=1999 |month=August |pmid=10452506 |doi= |url=}}</ref>
*[[Epithelioid angiosarcoma]].<ref name=pmid18318577/>
*[[Desmoplastic small round cell tumour]].<ref name=pmid18318577/>
*[[Anaplastic thyroid carcinoma]].<ref name=pmid18318577/>
*Biphasic [[malignant mesothelioma]].<ref name=pmid18318577/>
*[[Carcinosarcoma]].<ref name=pmid18318577/>
 
Common tumours that uncommonly have the pattern:
*[[Gastric adenocarcinoma]].<ref>URL: [http://cat.inist.fr/?aModele=afficheN&cpsidt=2504165 http://cat.inist.fr/?aModele=afficheN&cpsidt=2504165]. Accessed on: 26 April 2011.</ref>
 
==Sarcomas cytokeratins==
Most sarcomas are cytokeratin negative.
Most sarcomas are cytokeratin negative.


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