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Work with LifeSpan to design a custom immunohistochemistry to address your specific biological question. Outsource the entire localization process without having to worry about finding and characterizing target specific antibodies, sourcing and validating difficult-to-find tissues, and having the ability to interpret the resulting immunostaining in relation to complex human pathologies.

Test your therapeutic antibodies in immunohistochemistry against a broad panel of normal frozen human tissue types in order to determine potential unintended binding. Our non-GLP TCR services are designed on the FDA recommendation outlined in their "Points to Consider in the Manufacture and Testing of Monoclonal Antibody Products for Human Use".

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Other Cancers
Breast Colorectal Lung Prostate
Breast Cancer Immunohistochemistry Markers
IHC markers are used in both clinical and research settings to provide insights into a variety of processes that are of interest to breast cancer and disease research at large. Breast cancer, the most common malignancy in women worldwide, is classified by using microscopic morphologic criteria along with standard clinical immunohistochemistry markers for HER2 and ER/PR in order to predict if a patient’s tumor will respond to Herceptin or hormone therapy. IHC is further useful for determining rates of cell differentiation, elucidating molecular pathways, and highlighting the proteomics of tumor growth and metastatic potential. For example, IHC markers help distinguish in-situ from invasive carcinomas (KRT14 and KRT5), subtype ductal from lobular carcinomas (E-cadherin, p120, FOXA1, GATA3), determine mammary origin of a metastatic carcinoma (CK7, CK20, Mammaglobin A), and highlight tumor proliferation and apoptosis (Ki-67, BCL2, TP53). Furthermore, the myoepithelial markers SMA (Smooth Muscle Actin), Calponin, p63 and SMMHC can be used to determine whether or not a cancer has invaded, since benign and early lesions have an intact myoepithelial layer surrounding breast glands.

Targeting pathways through IHC:
IHC markers can be used to identify the deregulation or pathogenic activation of various cell-cycle pathways in breast cancer. These include BCL2, an anti-apoptotic protein which promotes...





Primary IHC Markers In Breast Cancer

ERBB2 / HER2
HER2 (ERBB2) is a tyrosine kinase/ epidermal growth factor receptor that is overexpressed and mutated in approximately 10-20% of breast cancers (Zaha, 2014). ERBB2 (HER2) exhibits positive membranous staining in malignant cells, where it promotes cancer cell growth. It is associated with more aggressive tumors. Immunohistochemistry staining of ERBB2 is used alongside the proteins ER (estrogen receptor), PR (progesterone receptor) and Ki-67 to classify different subtypes of breast cancer, and it is a widely used prognostic marker for breast cancer, as levels of ERBB2 expression predict a patient’s response to Herceptin therapy.
Staining: While this target can show either cytoplasmic or membranous staining, only membranous staining is relevant for cancer.

LSBio's recommended antibody to HER2 for use in immunohistochemistry is HER2 Antibody LS‑B2133.
Click here for specifications and further information on this antibody.

Estrogen Receptor / ESR1
ER (Estrogen receptor / ESR1) is a biomarker that is prognostic for breast cancer and predicts response to hormonal therapy. Estrogen receptor is a nuclear hormone receptor with nuclear staining in malignant breast cancer cells, and usually has higher levels of expression in Luminal A subtypes compared to others (Jeselsohn, 2015). Levels of expression of estrogen receptor are used in conjunction with progesterone receptor (PR), HER2 and Ki-67 expression levels to subtype breast cancers for different downstream treatments. Most breast cancers have positive expression of ER protein, primarily in luminal tissues where the luminal A subtype sees high levels of expression (Jeselsohn, 2015; Yersal, 2014).
Staining: Staining for this target is expected to be nuclear.

LSBio's recommended antibody to ER for use in immunohistochemistry is ER Antibody LS‑B10527.
Click here for specifications and further information on this antibody.

Progesterone Receptor / PGR
PR (progesterone receptor / PGR) is a biomarker that is prognostic for breast cancer and predicts response to hormonal therapy. Progesterone receptor is a nuclear hormone with nuclear staining in malignant breast cancer cells. Immunohistochemistry staining of PR is used alongside estrogen receptor (ER), HER2 and Ki-67 expression levels to subtype breast cancers for different downstream treatments. PR has been found to modulate the behavior of estrogen receptor protein and impede the growth of ER positive tumors, which coincides with the typically better prognosis of ER+, PR+ breast cancers when compared to other subtypes (Mohammed, 2015).
Staining: Staining for this target is expected to be nuclear.

LSBio's recommended antibody to PR for use in immunohistochemistry is PR Antibody LS‑B2983.
Click here for specifications and further information on this antibody.

TP53
TP53 is a tumor suppressor that may be used as a marker for estrogen and progesterone receptor negative high grade breast cancers. It is associated with basal subtypes, where it may have aberrant or positive expression (Zaha, 2014). High levels of TP53 protein are often found in triple negative breast cancers (TNBC) alongside high levels of Ki-67. In TNBC, TP53 staining correlates with tumor grade and worse prognosis (Pan, 2017).
Staining: TP53 staining is typically nuclear, but antibodies to this target can also show weaker cytoplasmic staining.

LSBio's recommended antibody to TP53 for use in immunohistochemistry is TP53 Antibody LS‑C172956.
Click here for specifications and further information on this antibody.

EGFR
EGFR protein regulates a number of fundamental cell cycle pathways and is involved in migration and tumor invasion. Gene amplification of EGFR is a frequent occurrence in some types of breast cancer and also in numerous other tissues. Roughly half of triple negative and also IBC (inflammatory breast cancer) cases show overexpression of this protein (Masuda, 2012). Expression is generally associated with the basal subtype but is also seen in some luminal B tumors, and is correlated with lower ER / PR expression (Changavi, 2015).
Staining: This protein has membranous and cytoplasmic staining in IHC.

LSBio's recommended antibody to EGFR for use in immunohistochemistry is EGFR Antibody LS‑B2914.
Click here for specifications and further information on this antibody.

BRCA1
BRCA1 is a multifunctional protein involved in DNA repair, tumor suppression and cell replication, whose dysfunction through inherited or somatic mutation or through epigenetic silencing is the oncogenic source of a certain percentage of breast cancers (Romagnolo, 2015). Mutations in this gene confer high risk for both breast cancer and ovarian cancer, and thus immunohistochemistry staining and testing for wild type and mutated forms of this repair gene are necessary for diagnosis and downstream treatment (Anantha, 2017).
Staining: This protein has nuclear and cytoplasmic staining in IHC depending upon the isoform.

LSBio's recommended antibody to BRCA1 for use in immunohistochemistry is BRCA1 Antibody LS‑B3772.
Click here for specifications and further information on this antibody.

APOBEC3B
APOBEC3B is a repair gene and cytidine deaminase involved in somatic hypermutation. The deregulation or dysfunction of APOBEC3B and other members of the APOBEC family has been implicated as a direct source of mutagenesis in breast and other cancers (Nik-Zainal, 2012; McBride, 2008; Hwang, 2015). APOBEC3B is upregulated in a number of breast cancers, and this upregulation correlates with a mutation spectrum (kataegis) in these tumors consistent with APOBEC function and may be a simultaneous or downstream consequence of ERBB2 amplification (Nik-Zainal, 2012; Kanu, 2016).
Staining: Staining for APOBEC3B is expected to be nuclear.

LSBio's recommended antibody to APOBEC3B for use in immunohistochemistry is APOBEC3B Antibody LS‑B12051.
Click here for specifications and further information on this antibody.

Proliferation Markers In Breast Cancer

Ki-67 (MKI67)
Ki-67 (MKI67) is a marker for proliferation in breast cancer cells and many other tumor and tissue types. The degree of expression of Ki-67 is used in conjunction with ER, PR and HER2 expression levels to subtype breast cancers. Higher levels of this protein are correlated with increased rates of proliferation (Zaha, 2014), absence of ER and PR and poor prognosis, and staining for Ki-67 in immunohistochemistry is thus important for determining the necessary treatment (Zorka, 2014).
Staining: Staining for this target is expected to be nuclear.

LSBio's recommended antibody to Ki-67 for use in immunohistochemistry is Ki-67 Antibody LS‑B3321.
Click here for specifications and further information on this antibody.

Cell-Type Specific Markers In Breast Cancer

CNN1 (Calponin)
CNN1 (calponin) is a myoepithelial marker in breast cancer with functional roles in proliferation, angiogenesis and migration (O’Kelly, 2008). In immunohistochemistry staining, calponin is found circulating the nucleus in the cytoplasm of myoepithelial cells (Zaha, 2014).

LSBio's recommended antibody to Calponin for use in immunohistochemistry is Calponin Antibody LS‑B4304.
Click here for specifications and further information on this antibody.

Smooth Muscle Actin (SMA / ACTA2)
Smooth Muscle Actin (SMA / ACTA2) is a myoepithelial marker for normal and cancerous breast tissue. Smooth muscle actin is often used alongside SMMHC, calponin and cytokines like CK5 and CK17 to distinguish myoephithelial cells from ductal carcinoma cells, which are negative for these proteins (Zaha, 2014). High levels of smooth muscle actin expression are correlated with poorer prognosis in breast cancers positive for EGFR and ERBB2; breast cancers with overexpression of these proteins see upregulation of ACTA2 likely due to its regulation by the upstream transcription activator STAT1. Overexpression of ACTA2 is correlated with an increase in invasive potential through its functions in the epithelial to mesenchymal transition (Jeon, 2016).
Staining: Staining for this target is cytoplasmic.

LSBio's recommended antibody to SMA for use in immunohistochemistry is SMA Antibody LS‑B7351.
Click here for specifications and further information on this antibody.

SMMHC
SMMHC (smooth muscle myosin heavy chain / MYH11) is a myoepithelial breast cancer marker. It is overexpressed in HER2-positive, estrogen receptor- and progesterone receptor-negative breast tumors and under-expressed in triple negative breast cancers (Li, 2016). As a myoepithelial marker, MYH11 tends to provide more sensitive results with less myofibroblast cross-reactivity when compared to biomarkers like calponin and smooth muscle actin. It can be used to illustrate ductal wall stability, as ductal tumor cells usually lack expression of MYH11 (Zaha, 2014).
Staining: Staining for this target is expected to be cytoplasmic.

LSBio's recommended antibody to SMMHC for use in immunohistochemistry is SMMHC Antibody LS‑B5148.
Click here for specifications and further information on this antibody.

CK5 (KRT5)
CK5 (KRT5) is a core basal-like and myoepithelial marker alongside EGFR in the immunohistochemistry of breast cancer (Yang, 2011). It has been found to have increased expression in luminal cells of adenoid cystic carcinoma (Nakai, 2016) and in KRT5 positive, estrogen receptor (ER) and progesterone receptor (PR) negative cells within luminal tumors have been correlated with treatment resistance and increased invasiveness (Axlund, 2013; Kabos, 2011).
Staining: Staining for this target is expected to be cytoplasmic.

LSBio's recommended antibody to CK5 for use in immunohistochemistry is CK5 Antibody LS‑B3359.
Click here for specifications and further information on this antibody.

CK7 (KRT7)
CK7 (KRT7) is a luminal cell biomarker for breast cancer (Abd El-Rehim, 2004). Cytokeratins are intermediate filaments that are involved in cytoskeletal integrity. This keratin is helpful for distinguishing Paget's disease (breast cancer in the skin) from melanoma. In Paget’s disease, CK7 highlights malignant breast cancer cells in the epidermis (Karakas, 2011; Smith, 1997).
Staining: Staining for this target is expected to be cytoplasmic.

LSBio's recommended antibody to CK7 for use in immunohistochemistry is CK7 Antibody LS‑B7164.
Click here for specifications and further information on this antibody.

CK14 (KRT14)
CK14 (KRT14) is a basal-like and myoepithelial marker for normal and cancer tissues of the breast. CK14 expression is linked with metastasis; a study from 2016 by Kevin J. Cheung et al found that metastatic polyclonal tumors shared high levels of KRT14 expression, indicating it as a biomarker for divergent invasive cancers in distant organs that followed an initial “collective invasion” into the stroma (Cheung, 2016). They found a drastic increase in CK14 expression in circulating tumor cells relative to primary tumors. CK14 may thus be an effective target not just as a myoepithelial marker but also for highly invasive metastatic polyclonal breast cancers.
Staining: Staining for this target is predominantly cytoplasmic.

LSBio's recommended antibody to CK14 for use in immunohistochemistry is CK14 Antibody LS‑B3916.
Click here for specifications and further information on this antibody.

CK20 (KRT20)
CK20 (KRT20) is an epithelial marker often used together with KRT7 (CK7) when trying to determine a metastatic carcinoma’s point of origin, and a CK7 positive, CK20 negative staining pattern is present in many breast cancers (Tsao, 2007). CK20 may be also be a useful marker for circulating tumor cells in breast cancer patients, and higher levels of expression in the peripheral blood have been found to be correlated with ER-negative high grade tumors and with lymph node metastases (Tunca, 2012; Lasa, 2013). Cytokeratins are intermediate filaments that contribute to cytoskeletal integrity in epithelial cell types, and cytokeratin 20 localizes to the cytoplasm.
Staining: Staining for this target is expected to be cytoplasmic.

LSBio's recommended antibody to CK20 for use in immunohistochemistry is CK20 Antibody LS‑B10488.
Click here for specifications and further information on this antibody.

E-Cadherin (CDH1)
E-cadherin (CDH1), a cadherin involved in cell to cell adhesion, sees consistent loss of expression in invasive lobular carcinoma of the breast and this coincides with the induction of metastatic and invasive properties in lobular tumors (Ciriello, 2015). CDH1 is often knocked out in ERBB2/HER2- negative, estrogen receptor-positive invasive lobular cancers (Hugo, 2017) and this downregulation is a predictor of poor prognosis (Li, 2017). A study from 2017 looking at the MDA-MB-468 human breast cancer cell line found that e-cadherin knockdown is specifically correlated with invasion, while higher expression profiles are more closely linked with higher proliferation (Ping, 2016), highlighting its utility as a marker in immunohistochemistry staining of invasive lobular tumors.
Staining: Cadherins typically show membranous staining in immunohistochemistry.

LSBio's recommended antibody to E‑cadherin for use in immunohistochemistry is E‑cadherin Antibody LS‑B4674.
Click here for specifications and further information on this antibody.

p120 (CTNND1)
p120 (CTNND1) may be used alongside e-cadherin (CDH1) in immunohistochemistry as a marker for lobular breast carcinoma and has been found to be a useful biomarker for early lobular lesions (Dabbs, 2007). Alongside downregulation of e-cadherin, immunohistochemistry staining of p120 shows it to be strongly positive in lobular tumors, with redistribution from the membrane to the cytoplasm (Li, 2014; Li, 2010).
Staining: Staining for this target is expected to be nuclear.

LSBio's recommended antibody to p120 for use in immunohistochemistry is p120 Antibody LS‑B14422.
Click here for specifications and further information on this antibody.

FOXA1
FOXA1 is a transcription factor involved in differentiation that is necessary for estrogen receptor (ER/ESR1) chromatin interaction and regulates many of the same genes. It is a useful marker for luminal breast cancers, as it is often expressed in luminal subtypes independent of ER expression and it does not see expression in basal subtypes (Bernardo, 2013). In ER-negative tumors, a lack of FOXA1 expression is associated with worse prognosis, as loss of FOXA1 is associated with the consequential expression of metastases-prone, basal-specific proteins that it normally acts to directly repress (Bernardo, 2013; Albergaria, 2009; Gong, 2014).

LSBio's recommended antibody to FOXA1 for use in immunohistochemistry is FOXA1 Antibody LS‑B4356.
Click here for specifications and further information on this antibody.

GATA3
The protein GATA3 is a transcription factor and is a useful biomarker for breast cancer. It has been found to be significantly mutated in luminal breast cancers (Goncalves, 2014), and it is also regularly highly expressed in breast carcinoma. It stains at high levels of expression across many subtypes including triple-negative breast cancers (Kandalaft, 2016) and for both primary and metastatic carcinomas (Sangoi, 2016), and it is considered a biomarker for the Luminal A subtype of epithelial cells (Yersal, 2014).
Staining: Staining for this target is expected to be nuclear.

LSBio's recommended antibody to GATA3 for use in immunohistochemistry is GATA3 Antibody LS‑B4163.
Click here for specifications and further information on this antibody.

Apoptosis and Angiogenesis Markers In Breast Cancer

VEGFA
VEGFA protein is a marker for tumorigenesis that is involved in angiogenesis and proliferation and is regularly upregulated in breast and other cancers. VEGFA is consistently expressed throughout tumorigenesis and metastasis at higher levels than normal tissue, and seems to be particularly overexpressed in triple-negative breast cancers (Taneja, 2010). VEGFA is a growth factor in vascular endothelial cells, where it activates cellular proliferation, angiogenesis and migration (O’Leary, 2016). VEGFA is involved in activating PI3K-Akt, MEK-ERK and other downstream signaling pathways, and as an actor in angiogenesis it promotes an increase in microvessel density when overexpressed in cancer (Taneja, 2010).
Staining: Staining for this target is a secreted cytokine, and it can show both cytoplasmic and extracellular staining.

LSBio's recommended antibody to VEGFA for use in immunohistochemistry is VEGFA Antibody LS‑B7747.
Click here for specifications and further information on this antibody.

BCL2
BCL2 is a marker of apoptosis in breast cancer, where overexpression of this protein is associated with a more favorable prognostic outcome in estrogen receptor- (ER) positive patients. Despite this, the function of BCL2 is anti-apoptotic and it is considered an oncogene (Hwang, 2017), and ER-negative, BCL2-positive patients have been shown to have worse outcomes (Zaha, 2014). It is a useful marker for specifically the luminal A subtype of breast cancer (Yersal, 2014; Eom, 2016). BCL2 staining is typically cytoplasmic, but can also localize to membranes.

LSBio's recommended antibody to BCL2 for use in immunohistochemistry is BCL2 Antibody LS‑B1173.
Click here for specifications and further information on this antibody.

CD31
CD31 is an angiogenesis marker in breast cancer, and increased staining of vessels within lymph nodes is an indicator of potential lymph node metastases of invasive ductal carcinoma (Popiela, 2008; Zaha, 2014). This protein is expressed in endothelial cells within capillaries and vessels. CD31 is a cellular adhesion molecule, and staining is typically membranous.

LSBio's recommended antibody to CD31 for use in immunohistochemistry is CD31 Antibody LS‑B3446.
Click here for specifications and further information on this antibody.

CD34
CD34 is a hematopoietic stem cell marker/adhesion protein that is also expressed in endothelium, where staining is typically membranous. This protein is also occasionally expressed in fibroblasts, and is present in the cytoplasm of mesenchymal cells surrounding benign glandular tissue in the breast. Consistent loss of expression in breast mesenchymal fibroblasts is associated with high grade, malignant breast cancers (Hua, 2011). Loss of expression of this protein in the stroma coincides with expression of smooth muscle actin and the adoption of invasive properties in ductal tumor cells (Catteau, 2013).

LSBio's recommended antibody to CD34 for use in immunohistochemistry is CD34 Antibody LS‑B2652.
Click here for specifications and further information on this antibody.

Metastatic Markers In Breast Cancer

SIAH2
SIAH2 is a novel target in breast and other cancers; in a study on advanced and metastatic breast cancer, Siewertz van Reesama et al found that both SIAH and EGFR outperform standard breast cancer biomarkers in predicting advanced stages of metastasis. SIAH2 is a downstream member of the RAS pathway, where it is required for signal transduction (Van Reesema, 2016). SIAH2 expression acts as a sign of activation of the RAS pathway (Van Reesema, 2016), and its deficiency has been found to reduce MAPK signaling (Ahmed, 2008). SIAH2 has been found to be overexpressed in invasive breast cancers versus ductal carcinomas and normal tissue, where it may cause aberrant activation of the ERK pathway, encouraging proliferation and simultaneous dysregulation of apoptotic signaling (Sun, 2016).
Staining: Staining for this target can be both cytoplasmic and nuclear.

LSBio's recommended antibody to SIAH2 for use in immunohistochemistry is SIAH2 Antibody LS‑C141889.
Click here for specifications and further information on this antibody.

Prolactin-induced protein (PIP / GCDFP-15)
Prolactin-induced protein (PIP / GCDFP-15) is a secreted protein produced by benign and malignant salivary gland and breast tissue. PIP is overexpressed in many breast carcinomas, where increased expression has been found to increase the cell adhesive and proliferative properties of malignant cells (Vanneste 2015; Naderi 2015).
Staining: This target typically stains secretions (may appear cytoplasmic, membranous, and/or extracellular).

LSBio's recommended antibody to PIP / GCDFP‑15 for use in immunohistochemistry is PIP / GCDFP‑15 Antibody LS‑B2498.
Click here for specifications and further information on this antibody.

Mammaglobin A (SCGB2A2)
Mammaglobin A (SCGB2A2) is a breast cancer biomarker that is tissue specific to breast and highly expressed in breast cancers. Overexpression of this protein has been correlated with proliferative and invasive properties in tumor cells (Picot, 2016), and coincides with simultaneous upregulation of Ki-67 (MKI67) protein – these two markers combined can be a useful pair in tissue specific immunohistochemistry staining of breast tumors (Gargano, 2006).
Staining: Staining for this target is has been demonstrated to be cytoplasmic and in secretions.

LSBio's recommended antibody to SCGB2A2 for use in immunohistochemistry is SCGB2A2 Antibody LS‑B3007.
Click here for specifications and further information on this antibody.

TNBC Markers In Breast Cancer

PIM1
PIM1 is a marker in breast tumors with particular relevance as a critical proliferative regulator in triple-negative breast cancers (TNBC). PIM1 was found to regulate proliferation and apoptosis in TNBC, with overexpression that correlates with MYC-target transcription and tumor proliferation. It is a potential novel drug target in TNBC treatment (Brasó-Maristany, 2016).
Staining: Staining for PIM1 is expected to be cytoplasmic.

LSBio's recommended antibody to PIM1 for use in immunohistochemistry is PIM1 Antibody LS‑B5493.
Click here for specifications and further information on this antibody.


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