The assessment of cellular proteins is a routine part of modern pathology, particularly in the diagnosis of cancer. Immunohistochemistry (IHC) is a technique used to identify specific marker proteins within cells. This process uses antibodies that highlight these unique proteins, making them visible under a microscope. Cytokeratin 20 (CK20) is one such protein marker, and pathologists use its presence or absence to help determine the nature and origin of abnormal growths, especially when cancer has spread. A CK20 result provides a significant clue that guides further diagnostic and treatment decisions.
Understanding Cytokeratin 20
Cytokeratin 20 (CK20) is an intermediate filament protein that provides mechanical stability and structure within epithelial cells. The normal physiological distribution of CK20 is largely restricted to the epithelial cells lining the gastrointestinal tract, specifically the colon and rectum. It is also found in the urothelium, the specialized lining of the urinary tract, including the bladder, and in Merkel cells located in the basal layer of the skin.
When a cancer cell develops, it usually retains the protein expression pattern of the normal tissue from which it originated. Therefore, detecting CK20 in a tumor sample links the cancer back to one of these specific tissue types.
Why CK20 Testing is Performed
CK20 testing is primarily performed to help pathologists determine the original site of a tumor, which is particularly relevant in metastatic disease. Cancer cells that have spread to distant sites, such as the liver or lymph nodes, are known as metastases.
The test is frequently utilized in the workup for Cancer of Unknown Primary (CUP), where a metastatic tumor is found but the location of the primary tumor is not immediately obvious. By identifying the specific proteins a metastatic tumor expresses, the pathologist can significantly narrow down the list of possible primary sites. CK20 is rarely used alone; it is typically included in a panel of immunohistochemical stains, most commonly alongside Cytokeratin 7 (CK7).
The combined CK7 and CK20 expression pattern acts as an internal map, suggesting a likely origin for the metastatic tumor. For example, a CK20 positive and CK7 negative tumor points toward a different set of primary sites than a tumor positive for both markers. This algorithmic approach helps direct the search for the primary tumor, which is necessary for effective treatment planning.
Interpreting a CK20 Positive Result
A CK20 positive result means the tumor cells are expressing the Cytokeratin 20 protein. This finding strongly suggests that the cancer originated from a tissue type that normally expresses CK20. The most common and significant association for a CK20-positive tumor is colorectal carcinoma.
In the vast majority of colorectal cancer cases, the tumor cells exhibit a specific staining profile: CK20 positive and CK7 negative (CK20+/CK7-). This pattern is highly characteristic of colon cancer and is a key indicator when analyzing a metastatic tumor found in a distant organ. The detection of this pattern in a liver lesion, for instance, provides strong evidence that the lesion is a metastasis from a primary colorectal tumor.
Another significant association for CK20 positivity is urothelial carcinoma. Urothelial tumors often show a CK20 positive and CK7 positive (CK20+/CK7+) profile, although expression can be variable depending on the tumor grade. Furthermore, Merkel cell carcinoma, a rare and aggressive form of skin cancer, is also characterized by strong positive staining for CK20.
Knowing the tumor’s origin dictates the treatment protocol. A metastatic tumor identified as originating from the colon will be treated with chemotherapy regimens specific to colorectal cancer. For example, a tumor with the CK20+/CK7- profile may prompt the use of colon cancer-specific drugs and further diagnostic procedures like a colonoscopy to locate the primary site.
What CK20 Negative Results Suggest
A CK20 negative result indicates that the tumor cells do not express the Cytokeratin 20 protein, or express it below the level of detection. This finding suggests that the tumor did not originate from the colon, rectum, or bladder, which are the main CK20-expressing sites.
When a tumor is CK20 negative, the pathologist examines the results of other markers in the panel, especially CK7, to continue the search for the primary site. Many common cancers are overwhelmingly CK20 negative, including breast adenocarcinoma, lung adenocarcinoma, and prostate cancer. These tumors are often characterized by a CK7 positive and CK20 negative (CK7+/CK20-) profile.
Other malignancies, such as renal cell carcinoma and thyroid carcinoma, are typically negative for both CK7 and CK20 (CK7-/CK20-). The CK20 negative finding acts as a filter, shifting the focus to other diagnostic possibilities, such as a primary site in the lung, breast, or ovary. The next step involves applying more specific immunohistochemical stains, such as TTF-1 for lung or thyroid origin, or GATA-3 for breast or urothelial origin, to confirm the suggested primary site.