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Antibody List, N - Z Antibodies

S100P

S100P (placental S100) is a member of the S100 family.  It has been identified in human placenta and is expressed in a multitude of cancer types including: bladder, breast, esophagus, colon, lung, pancreatic, ovarian, hepatocellular (HCC), cholangiocarcinoma, and prostate (Yuan et al.).  Interesting, Mohanty, et al. found S100P to be a relatively sensitive and specific marker for urothelial carcinoma in the differential of urothelial carcinoma vs. poorly differentiated prostate adenocarcinoma of the bladder neck (88% sensitive, 100% specific, N=16).
 
Practically, S100P may have some useful benefit in a limited differential setting, but given its general lack of specificity would probably not be significantly helpful in the setting of a large differential diagnosis.
 
Yuan, et al. did find S100P expression to be an independent poor prognostic indicator in HCC with early tumor recurrence or high tumor stage.
Microscopic Images
S100P - Placenta
S100P expression in placental tissue (good control)
S100P - Prostate Adenocarcinoma
S100P expression in metastatic prostate adenocarcinoma.
References
 
Yuan, R.-H., Chang, K.-T., Chen, Y.-L., Hsu, H.-C., Lee, P.-H., Lai, P.-L., & Jeng, Y.-M. (2013). S100P expression is a novel prognostic factor in hepatocellular carcinoma and predicts survival in patients with high tumor stage or early recurrent tumors. PloS One, 8(6), e65501. doi:10.1371/journal.pone.0065501
 
Mohanty SK, Smith SC, Chang E, et al. Evaluation of contemporary prostate and urothelial lineage biomarkers in a consecutive cohort of poorly differentiated bladder neck carcinomas. Am J Clin Pathol. 2014;142(2):173–183. doi:10.1309/AJCPK1OV6IMNPFGL. 
Antibody List, N - Z Antibodies

S-100

S-100 is a marker that is most commonly used to identify cells of neural origin, including melanocytes and melanoma.  S-100 is an antibody to the calcium-flux determinant protein, which is expressed by many different tissue types including: melanocytes, Schwann cells (nerve fibers), neural elements (astrocytes, ependyma, and oligodendroglia), Langerhans histiocytes, myoepithelial cells, reticulum cells, and salivary gland.  Unfortunately, this variability of specificity can make the use of the S-100 antibody in isolation “risky business.”  In fact, some carcinomas may express S-100.  Therefore, in the work-up of a poorly differentiated lesion, it should be part of a larger panel. 
 
S-100 expression can be nuclear and cytoplasmic.
Melanoma
S-100 is generally considered the most sensitive marker for melanoma (a few may argue vimentin), but has limitations in evaluation of lymph node tissue due to all of the background expression in dendritic cells.  MART-1 (Melan A) and HMB-45 are typically used more commonly in these situations.  As a general rule of thumb, the more epithelioid the melanoma, the more likely it will be to express MART-1 and HMB-45.  As melanomas become more “spindled” the less they tend to express HMB-45 and MART-1.  S-100 tends to retain expression in melanomas better as the pattern becomes more spindled compared to HMB-45 and MART-1
Normal expression may be seen in:
  • Melanocytes
  • Langerhans histiocytes
  • Cartilaginous cells
  • Adipocytes
  • Schwann cells
  • Astrocytes
  • Oligodendroglia
  • Ependyma
  • Eccrine glands
  • Reticulum cells
  • Salivary glands
  • Myoepithelial cells
Neoplasms which may express S-100:
  • Melanoma
  • Clear cell sarcoma
  • Glioma
  • Peripheral nerve sheath tumors
  • Poorly differentiated carcinomas (small subset) – breast, GU tract, pancreas, salivary gland, and sweat gland origin.
Microscopic Images
S-100 - Nevus
S-100 expression in nevus.
S-100 - Nerve
S-100 expression in nerve fiber.
S-100 - Melanoma
S-100 expression in melanoma (DAB).
S-100 - Melanoma
S-100 expression in a malignant melanoma.
S-100 - Granular Cell Tumor
S-100 expression in a granular cell tumor.
References
Wick, M. R. (2008). Immunohistochemical approaches to the diagnosis of undifferentiated malignant tumors. Annals of Diagnostic Pathology, 12(1), 72–84. doi:10.1016/j.anndiagpath.2007.10.003 
 
Kucher, C., Zhang, P. J., Acs, G., Roberts, S., & Xu, X. (2006). Can Melan-A replace S-100 and HMB-45 in the evaluation of sentinel lymph nodes from patients with malignant melanoma? Applied Immunohistochemistry & Molecular Morphology : AIMM / Official Publication of the Society for Applied Immunohistochemistry, 14(3), 324–327. 
Antibody List, N - Z Antibodies

Renal Cell Carcinoma Marker (RCC Ma)

Renal Cell Carcinoma Marker (RCC Ma) is a cytoplasmic marker that stains the renal proximal tubule brush border antigen.  The following table (McGregor, et al) shows the stain sensitivity (>10% tumor cell staining):
Tumor Type
Sensitivity
RCC Clear Cell
84%
RCC Papillary
96%
RCC Chromophobe
45%
RCC Sarcomatoid
25%
Collecting Duct Carcinoma
0%
Oncocytoma
0%
 
Sharma, S.G., et. al.  (PAX-2 and RCCma expression in various papillary tumors)
Tumor Type
No.
PAX2
RCCma
Papillary RCC
24
67%
96%
Ovarian Papillary Serous Carcinoma
10
40%
80%
Uterine Papillary Serous Carcinoma
9
56%
44%
Papillary Thyroid Carcinoma
9
0%
100%
Papillary Urothelial Carcinoma
10
0%
10%
Intraductal Papillary Mucinous Tumor of the Pancreas
2
0%
50%
Chroroid Plexus Papilloma
1
0%
100%
Pituitary Adenoma with Papillary Features
1
0%
100%
Lung Adenocarcinoma with Papillary Features
2
0%
50%
 
RCC Ma has been shown to be relatively specific for RCC in the metastatic setting, but is known to stain cells of other histogenesis (e.g. breast carcinoma, embryonal carcinoma, parathyroid adenomas, etc.).  RCC Ma is a useful marker, but not recommended to be used in isolation (especially papillary lesions).  It is also important to confirm the performance of this antibody within one’s laboratory because it has shown performance variability from laboratory to laboratory (author’s experience).  A useful panel for renal cell carcinoma includes CD10, vimentin, AE1/AE3, and RCC Ma.
Photomicrograph
Renal Cell Marker (RCC Ma) - Renal Cell Carcinoma
Renal Cell Marker (RCC Ma) – Metastatic Renal Cell Carcinoma
 Reference:
McGregor, D. K., Khurana, K. K., Cao, C., Tsao, C. C., Ayala, G., Krishnan, B., et al. (2001). Diagnosing primary and metastatic renal cell carcinoma: the use of the monoclonal antibody ‘Renal Cell Carcinoma Marker’. The American Journal of Surgical Pathology, 25(12), 1485–1492.
 
Sharma, S. G., Gokden, M., McKenney, J. K., Phan, D. C., Cox, R. M., Kelly, T., & Gokden, N. (2010). The utility of PAX-2 and renal cell carcinoma marker immunohistochemistry in distinguishing papillary renal cell carcinoma from nonrenal cell neoplasms with papillary features. Applied Immunohistochemistry & Molecular Morphology : AIMM / Official Publication of the Society for Applied Immunohistochemistry, 18(6), 494–498. doi:10.1097/PAI.0b013e3181e78ff8  
 
Pan, Z., Grizzle, W., & Hameed, O. (2013). Significant variation of immunohistochemical marker expression in paired primary and metastatic clear cell renal cell carcinomas. American Journal of Clinical Pathology, 140(3), 410–418. doi:10.1309/AJCP8DMPEIMVH6YP
 
Zhai, Q. J. (2010). Application of Immunohistochemistry to the Diagnosis of Kidney Tumors. Pathology Case Reviews, 15(1), 25–34. doi:10.1097/PCR.0b013e3181d51c70  
Antibody List, N - Z Antibodies

PSA

Prostate Specific Antigen (PSA) is a marker used to identify tumors of prostate epithelium origin. It is generally considered to be >95% sensitive for prostate carcinoma, and has better specificity that PSAP.  However, as the Gleason score increases, the sensitivity decreases.  This is important because it is not usually the well-differentiated tumors that cause diagnostic confusion, but the poorly differentiated ones.  In an article by Mohanty, PSA expression was in the range of 25% for poorly differentiated prostate carcinomas present in the bladder trigone area, but an article by Goldstein indicates the sensitivity may be closer to 50% in high Gleason score tumors.
 
Common expression patterns in carcinoma [Clin Cancer Res 2005;11(10) May 15, 2005]
Tumor
Expression (%)
Breast
0%
Colon
0%
Lung
<10%
Ovary
0%
Pancreas
0%
Stomach
<5%
Prostate
>95%
 
 
PSA expression and other markers as a function of Gleason score (Goldstein, NS)
Gleason Score
PSA
CK7
CK20
PAP
     6 (N=25)
100%
0%
0%
100%
     7 (N=50)
98%
0%
2%
100%
     8 (N=54)
56%
0%
4%
65%
     9 (N=58)
52%
10%
16%
74%
     10 (N=38)
47%
13%
26%
61%
Prostate specific antigen (PSA), Prostatic acid phosphatase (PAP). Reactivity was defined as >25% positive cells.
Microscopic Images
PSA - Prostate Adenocarcinoma
PSA expression in prostate adenocarcinoma.
PSA - Prostate
PSA expression in prostate.
PSA - Prostate Adenocarcinoma
PSA expression in prostate adenocarcinoma.
PSAP - Prostate
PSAP expression in prostate gland tissue (adenocarcinoma).
References
 Goldstein NS. Immunophenotypic characterization of 225 prostate adenocarcinomas with intermediate or high Gleason scores. Am J Clin Pathol. 2002;117(3):471–477. doi:10.1309/G6PR-Y774-X738-FG2K.
 
Mohanty SK, Smith SC, Chang E, et al. Evaluation of contemporary prostate and urothelial lineage biomarkers in a consecutive cohort of poorly differentiated bladder neck carcinomas. Am J Clin Pathol. 2014;142(2):173–183. doi:10.1309/AJCPK1OV6IMNPFGL.
 
Clin Cancer Res 2005;11(10) May 15, 2005
Antibody List, N - Z Antibodies

PSMA

Prostate-specific membrane antigen (PSMA) is a glycoprotein, which functions as folate hydrolase, and is very specific for prostate tissue (benign and malignant).  Expression can be seen with various patterns including: cytoplasmic and membraneous, cytoplasmic, apical, and apical/cytoplasmic.  It appears fairly specific for prostate, although Mhawech-Fauceglia, et al. found 17% of urothelial carcinomas to have cytoplasmic expression.  In non-prostate normal tissues, PSMA showed weak cytoplasmic expression in endometrial glands, testis, bladder, and kidney tubules.  Moderate cytoplasmic expression was seen in pancreas islets, GI tract ganglion cells, and brain, and strong cytoplasmic expression was seen in heart tissue.
 
Mhawech-Fauceglia, et al. only showed 66% sensitivity for PSMA, but this study was performed on 6 mm core punch tissue-microarray (TMA) using the YPSMA-1 clone (1:50, GeneTex, Inc., San Antonio, TX).  Mohanty, et. al. showed 100% sensitivity for PSMA in a study of poorly differentiated prostate andenocarcinomas of the bladder neck using the 1D6 clone (1:20, Novocastra, Leica, Buffalo Grove, IL).  It is unclear if the difference between the studies is the clone used, or that Mhawpch-Fauceglia, et al. used a small TMA, while Mohanty, et. al. used whole sections.  Additional study is required in this area, and it is advisable if one chooses to use this antibody (or bring it into their lab), one should verify the performance in-house.
 
The specificity of PSMA is a bit difficult to completely characterize.  Mhawpch-Fauceglia, et al. studied 987 benign tissues and 2,174 malignant tumors.  A small subset (usually 15% or less) of a wide variety of tumors showed some expression (usually weak).  Please refer to the references for a complete description beyond this brief summary.  Expanded data on the 1D6 clone, similar to the Mhawpch-Fauceglia et al. paper on the YPSMA-1 clone, is not available to our knowledge.
 
Study
Prostate
Adenocarcinoma
Urothelial
Carcinoma
Mhawech-Fauceglia, et. al.
(YPSMA-1, 1:50, GeneTex)
66% + (N=141)
17% + (N=346)
Mohanty, et. al.
(1D6, 1:20, Novocastra)
100% + (N=20)
0% + (N=16)
 
References:
 
Mohanty SK, Smith SC, Chang E, et al. Evaluation of contemporary prostate and urothelial lineage biomarkers in a consecutive cohort of poorly differentiated bladder neck carcinomas. Am J Clin Pathol. 2014;142(2):173–183. doi:10.1309/AJCPK1OV6IMNPFGL.
 
Mhawech-Fauceglia P, Zhang S, Terracciano L, et al. Prostate-specific membrane antigen (PSMA) protein expression in normal and neoplastic tissues and its sensitivity and specificity in prostate adenocarcinoma: an immunohistochemical study using mutiple tumour tissue microarray technique. Histopathology. 2007;50(4):472–483. doi:10.1111/j.1365-2559.2007.02635.x. 
Antibody List, N - Z Antibodies

Progesterone Receptor (PR)

Progesterone receptor (PR) is used along with ER as a prognostication marker in breast carcinoma.  Expression is determined by percent positive and intensity (1+, 2+, 3+).  PR is not as important of a prognostic marker compared to ER, but lower grade more differentiated tumors tend to show stronger expression of both ER and PR, and also have a better relative treatment outcome compared higher grade tumors.
 
A PR positive, ER negative, expression pattern should raise concern that either the slides were mislabeled, or the ER assay may not be performing properly.  Most believe that ER expression is required for PR expression.
 
Outside of being used as a breast predictive marker, PR is not used too much in routine diagnostic surgical pathology.
 
Summary
  • Nuclear Marker
  • Stain is reported as PERCENT STAINING OF TUMOR CELLS and STAIN INTENSITY (1+, 2+, 3+)
  • 1% or greater nuclear expression in tumor cells is considered positive
  • PR expression is a prognostic marker, and not directly used for eligibility to receive a specific treatment
  • PR expression without ER expression should raise significant concern that the ER and PR slides have been mixed up, or there is a problem with the ER assay.  Many scientists believe that ER expression is required for PR expression.
Photomicrographs
PR - Metastatic Breast Carcinoma
PR – Metastatic Breast Carcinoma (focal expression)
PR - Breast
PR – Breast Carcinoma (moderate to strong expression)
PR - Normal Breast
PR – Normal Breast
References
Hammond ME, et. al.  “ASCO-CAP Guideline Recommendations for IHC Testing of ER and PR in Breast Cancer”.  Arch Pathol Lab Med-Vol. 134, June 2010.
Antibody List, N - Z Antibodies

PIN-4

PIN-4 is a cocktail stain used in evaluation of prostate specimens, and contains antibodies CK5, CK14, p63, andP504S.  CK5 and CK14 are high molecular weight keratins, which are expressed in the basal layer of normal prostate glands.  p63 is also expressed in the nuclei of prostate basal epithelial cells.  Therefore, combining p63, CK5 and CK14 allows to increase the sensitivity in identifying a basal epithelial layer in prostate glands.  The absence of a basal epithelial layer around prostate epithelium is characteristic of an invasive prostate adenocarcinoma.
 
P504S is a racemase (AMACR), which is over-expressed in a significant percentage of prostate adenocarcinomas and high-grade-PIN.  Benign glands do not typically express P504S with rare exceptions.  It is also important to understand that P504S, while demonstrating good specificity for benign versus neoplastic prostate gland epithelium, is NOT specific to only neoplastic prostate epithelium.  Other (non-prostate) benign and neoplastic processes may express P504S (e.g. nephrogenic adenoma).
Microscopic Images
PIN-4 Prostate Adenocarcinoma
PIN-4 staining in prostate adenocarcinoma. AMACR (red) expression in neoplastic cells.
PIN-4 Benign Prostate
PIN-4 expression in benign prostate. HMWCK and p63 highlighting basal layer without significant expression of AMACR (red) in the epithelial cells.
H&E Prostate Adenocarcinoma
H&E section of prostate adenocarcinoma to compare with PIN-4 staining.
References
 Yang, X. J., Wu, C.-L., Woda, B. A., Dresser, K., Tretiakova, M., Fanger, G. R., & Jiang, Z. (2002). Expression of alpha-Methylacyl-CoA racemase (P504S) in atypical adenomatous hyperplasia of the prostate. The American Journal of Surgical Pathology, 26(7), 921–925. doi:10.1097/01.PAS.0000017328.13364.17
 
Luo, J., Zha, S., Gage, W. R., Dunn, T. A., Hicks, J. L., Bennett, C. J., et al. (2002). Alpha-methylacyl-CoA racemase: a new molecular marker for prostate cancer. Cancer Research, 62(8), 2220–2226.
 
Zhou, M., Chinnaiyan, A. M., Kleer, C. G., Lucas, P. C., & Rubin, M. A. (2002). Alpha-Methylacyl-CoA racemase: a novel tumor marker over-expressed in several human cancers and their precursor lesions. The American Journal of Surgical Pathology, 26(7), 926–931. doi:10.1097/01.PAS.0000018309.60184.52
 
Tacha, D. E., & Miller, R. T. (2004). Use of p63/P504S monoclonal antibody cocktail in immunohistochemical staining of prostate tissue. Applied Immunohistochemistry & Molecular Morphology : AIMM / Official Publication of the Society for Applied Immunohistochemistry, 12(1), 75–78. 
 
Jiang, Z., Li, C., Fischer, A., Dresser, K., & Woda, B. A. (2005). Using an AMACR (P504S)/34bE12/p63 Cocktail for the Detection of Small Focal Prostate Carcinoma in Needle Biopsy Specimens. American Journal of Clinical Pathology, 123(2), 231–236. doi:10.1309/1G1NK9DBGFNB792L 
Antibody List, N - Z Antibodies

p501s (prostein)

p501s is an antibody used to detect the expression of prostein, which is highly sensitive and specific for prostate gland epithelium. Kilos, et. al. described an 87% sensitivity (N=53) of the 10E3-G4-D3 antibody clone for prostate tumors, and negativity in 4,635 non-prostate normal and malignant tissues throughout an extensive diversity of tissue and tumor types.  Detection of expression of prostein appears to be independent of Gleason score.  This is important because PSA and PSAP have struggled to have sensitivity over 50% in high Gleason score prostate carcinomas, which can be diagnostically challenging.

Continue reading p501s (prostein) →

Antibody List, N - Z Antibodies

p63

p63 is a nuclear transcription marker used in the identification of tumors subtypes and tissue structures such as:  myoepithelial cell layer (breast), basal cell layer (prostate), salivary gland tumors, squamous cell carcinoma (most sensitive marker), skin appendage tumors, and urothelial carcinoma.  As a general rule, transcription markers like p63 show a strong diffuse nuclear expression diagnostically.
Diagnostic Applications
Cell Differentiation
Comments
Myoepithelial Cells
Will stain cells in tumors of myoepithelial origin such as salivary gland tumors.
Urothelial Cells
70-100% of urothelial carcinomas will express p63
Squamous Cells
Squamous Cell Carcinomas from most locations will mark with p63 resulting in a high sensitivity.
Stromal Invasion
p63 can be very helpful to define stromal invasion, as it normally marks myoepithelial cells in breast tissue and basal cells in prostate tissue, which are lost in invasive carcinomas.  Generally recommended to be used with a cytoplasmic myoepithelial marker in breast lesions (e.g. smooth muscle myosin or calponin).
 
p63 expression in selected tumors, may have prognostic implications for Breast, Lung, and Bladder carcinomas.
GU Pathology
p63 is expressed in a high percentage of urothelial carcinomas, but is negative in renal cell carcinomas.  A small percentage of collecting duct carcinomas (14%) have been reported to express p63.  p63 may be helpful in differentiation of renal urothelial carcinoma and poorly differentiated renal cell carcinoma (RCC).
 
Arch Pathol Lab Med-Vol.135, January, 2011
Tumor
p63 Expression (%)
Urothelial Carcinoma
70-100%
Renal Cell Carcinoma
0%
Sarcomatoid Urothelial Carcinoma
50%
Collecting Duct Carcinoma
14%
Placental Sit Trophoblastic Tumor
p63 is expressed in intermediate trophoblasts associated with placental site nodules, but is negative in placental site trophoblastic tumors (epithelioid trohphoblastic tumors also express p63) [Mittal, et. al.].
Undifferentiated Carcinomas
CK5/6 co-expression with p63 is a sensitive (77%) and specific (96%) marker for squamous cell carcinoma.   p63 appears to be very specific for squamous and urothelial origin.  Only rare other non-squamous cell carcinomas show >50% expression of p63. [Kaufman, O., et. al.]
Small Cell Carcinoma
Small cell carcinomas express p63 in approximately 77% of cases (n=14). [Au, NH, et. al.]  This could be a potential pitfall if one is considering a poorly differentiated squamous cell carcinoma and not a poorly differentiated neuroendocrine carcinoma. 
Microscopic Images
p63 - Lung Adenocarcinoma
Variable subset nuclear expression of p63 in a lung adenocarcinoma, which is characteristic in a subset of cases. SCC expression should be diffuse and consistent.
p63 - Benign Prostate
p63 highlighting the basal layer of benign prostate gland epithelium.
p63-CK5 (double stain) lung squamous cell carcinoma
Co-expression of CK5 (red) and p63 (DAB) in a lung squamous cell carcinoma. Note the diffuse consistent expression of p63.
PIN-4 Benign Prostate
PIN-4 expression in benign prostate. HMWCK and p63 highlighting basal layer without significant expression of AMACR (red) in the epithelial cells.
p63 - LCIS
p63 highlighting nuclear expression in the myoepithelial cell layer surrounding LCIS. Best used in combination with another cytoplasmic myoepithelial marker (e.g. smooth muscle myosin, calponin, etc.).
References
Hadi, AIMM Annual Meeting, “The Thirty Most Important Antibodies”, presentation, 2011.
 
Truong, LD, et. al. “Immunohistochemical Diagnosis of Renal Neoplasms.” Archives of Pathology and Laboratory Medicine. 2011;135:92-109.
 
Mittal, K, et. al. “Aplplication of Immunohistochemistry to Gynecologic Pathology.”  Archives of Pathology and Laboratory Medicine. Vol. 132, March 2008.
 
Kaufmann, O., et. al. “Value of p63 and CK 5/6 as IHC Markers for the Differential Dx. of Poorly Differentiated and Undifferentiated Carcinomas.” American Journal of Clinical Pathology. 2001;116:823-830
 
Au NHC, Gown AM, Cheang M, et al. P63 expression in lung carcinoma: a tissue microarray study of 408 cases. Appl Immunohistochem Mol Morphol. 2004;12(3):240–247.
 
Zhao L, Yang X, Khan A, Kandil D. Diagnostic role of immunohistochemistry in the evaluation of breast pathology specimens. Arch Pathol Lab Med. 2014;138: 16–24. doi:10.5858/arpa.2012-0440-RA