CD31, also known as Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1), is a protein found primarily on the surface of endothelial cells. These cells form the inner lining of all blood vessels and lymphatic vessels in the body. The molecule is also present on circulating cells like platelets, monocytes, neutrophils, and certain T-cells. Due to its concentrated presence on the vascular lining, CD31 acts as a highly specific marker for identifying the body’s entire network of blood vessels.
Visualizing this protein in a tissue sample is accomplished through immunohistochemical staining, a laboratory technique used in pathology. This technique uses molecular probes to highlight and localize specific proteins within a tissue section. This allows doctors to view cellular structures and protein expression patterns under a microscope. By mapping the presence and distribution of CD31, pathologists gain insights into the structure of the vascular system within a tissue sample.
The Biological Function of CD31
CD31 functions primarily to maintain the integrity and function of the vascular system. As a cell adhesion molecule belonging to the immunoglobulin superfamily, CD31 is concentrated at the borders where individual endothelial cells meet, forming intercellular junctions. These junctions are secured through a homophilic interaction, meaning CD31 molecules on one cell bind to those on an adjacent cell. This specialized bonding helps regulate the vascular barrier, ensuring the vessel wall remains intact and resists mechanical forces from blood flow.
CD31 also plays a significant role in the immune system by managing the movement of white blood cells. It is involved in a process called leukocyte transendothelial migration, often referred to as diapedesis, where immune cells cross the vessel wall from the bloodstream into surrounding tissues. The molecule facilitates this passage by modulating the activity of other adhesion molecules. This allows immune cells to squeeze through the endothelial lining during inflammation or immune responses.
The Process of Identifying CD31 Through Staining
The visualization of CD31 in a tissue sample relies on the specificity of antibodies for their target protein, a process known as immunohistochemistry. The process begins when a tissue section, typically from a biopsy, is prepared on a glass slide. A primary antibody, engineered to selectively bind only to the CD31 protein, is introduced to the tissue. This antibody acts as a molecular beacon, attaching itself wherever CD31 is present on the cell surfaces.
Because the primary antibody is colorless, a detection system must be used to make its location visible. A secondary antibody, designed to bind to the first, is introduced and linked to an enzyme, such as horseradish peroxidase (HRP) or alkaline phosphatase (AP). Finally, a chromogenic substrate is added, which reacts with the attached enzyme to produce a localized color change, usually a brown or red stain. The result is a distinct colored outline of all endothelial cells, effectively mapping the entire vascular network for examination.
Clinical Applications in Diagnosis
The specific staining pattern provided by CD31 is frequently employed in diagnostic pathology to identify the origin of abnormal cell growths. Its most frequent use is confirming the endothelial nature of a tumor, which is helpful in classifying vascular neoplasms.
Tumor Classification and Differentiation
Pathologists use CD31 staining to distinguish between different types of vascular growths. For instance, it helps differentiate a benign blood vessel tumor, such as a hemangioma, from an aggressive vascular malignancy, like an angiosarcoma. In these malignancies, the tumor cells themselves will stain positive for CD31.
The stain is also used to differentiate vascular tumors from other non-vascular growths that may look similar under a standard stain. Confirming that the abnormal cells are positive for CD31 establishes that the growth is of endothelial origin. This specificity narrows the diagnostic possibilities, particularly when dealing with soft tissue tumors.
Assessing Microvessel Density (MVD)
CD31 staining is a standard method for quantifying the density of blood vessels within a tissue sample, a measurement often called microvessel density (MVD). In oncology, elevated MVD within a tumor is a direct indication of angiogenesis, the formation of new blood vessels that tumors require to grow and spread.
Pathologists can count the number of CD31-positive vessels in specific fields of view to assess a tumor’s capacity for growth and its potential for invasion or metastasis. Measuring MVD provides prognostic information, as a high vessel count often correlates with a more aggressive disease course in various cancers, including colorectal and breast carcinoma.
Diagnostic Caveats
Pathologists must interpret the results carefully, as CD31 is not exclusive to endothelial cells and can also mark certain immune cells, such as histiocytes. For this reason, CD31 is often used as part of a panel of markers to ensure the highest level of diagnostic accuracy.