BerEP4

BerEP4 is an antibody that pathologists use to identify a specific protein found on the surface of many types of epithelial cells. This protein is called epithelial cell adhesion molecule (EpCAM). EpCAM helps cells stick together, which is important for maintaining the structure and function of many tissues. Pathologists commonly use BerEP4 testing to help determine the type and origin of various tumors.

What types of normal cells and tissues express BerEP4?

In normal, healthy tissues, BerEP4 is typically found along the basolateral surfaces (side and bottom edges) of epithelial cells. These cells line the surfaces and internal cavities of many organs, such as the intestines and certain glands.

How do pathologists test for BerEP4?

Pathologists test for BerEP4 using immunohistochemistry (IHC). This involves applying the BerEP4 antibody to a tissue sample. If the targeted EpCAM protein is present, the antibody binds to it, causing the cells to change color when viewed under a microscope. The staining usually appears along the cell membranes (outer edges) of the tumor cells. Pathologists assess the presence, intensity, and pattern of staining to determine if the cells express BerEP4.

What types of tumors express BerEP4?

BerEP4 is commonly expressed in many carcinomas, a type of cancer that begins in epithelial cells. Tumors that frequently express BerEP4 include:

• Basal cell carcinoma of the skin: Almost always strongly positive, helping distinguish it from squamous cell carcinoma.

• Basosquamous carcinoma of the skin: Typically positive, aiding differentiation from pure squamous cell carcinoma.

• Adenocarcinoma of the lung: Usually positive, helping pathologists differentiate lung adenocarcinoma from malignant mesothelioma (which is usually negative).

• Metastatic adenocarcinoma to the liver or cholangiocarcinoma: Usually positive, helping distinguish these tumors from hepatocellular carcinoma, which is usually negative.

• Breast, ovarian, gallbladder, and pancreatic cancers: Positivity may indicate a more aggressive disease course or poorer prognosis.

• Renal cell carcinomas: Chromophobe renal cell carcinoma (75%), papillary renal cell carcinoma (55%), and a smaller proportion of clear cell renal carcinomas (18%) and metastatic renal carcinomas (14%).

• Synovial sarcoma: Despite being a sarcoma (which typically does not express epithelial markers), synovial sarcoma commonly expresses BerEP4.

What types of tumors do not express BerEP4?

Many tumor types are typically negative for BerEP4 staining, including:

• Malignant mesothelioma

• Lymphomas

• Most soft tissue sarcomas (except synovial sarcoma)

• Adenomatoid tumors

• Renal oncocytomas

Normal tissues such as epidermal keratinocytes, gastric parietal cells, hepatocytes, myoepithelial cells, squamous epithelia, and thymic cortical epithelium also typically do not express BerEP4.

Interpreting your BerEP4 results

When interpreting BerEP4 results, pathologists look for membranous staining (staining of the outer edges of cells). A positive BerEP4 test typically indicates that the tumor originates from epithelial tissue or is one of the cancer types listed above that commonly express this marker. A negative BerEP4 result can help rule out certain epithelial cancers and support diagnoses such as malignant mesothelioma or specific renal tumors.

Your pathology report may describe the intensity (strong, moderate, weak) and pattern of staining. Positive membranous staining usually indicates epithelial origin, helping your doctor make a more accurate diagnosis and select the appropriate treatment.

Questions for your doctor

• Was my tumor positive or negative for BerEP4?

• What does the BerEP4 result indicate about the type and origin of my tumor?

• How does the BerEP4 result affect my treatment options?

• Should additional tests be performed to confirm my diagnosis?

• Is the presence or absence of BerEP4 linked to my prognosis?