Cytokeratin 7 (CK7) is a structural protein and a key component of the cellular skeleton. It belongs to the intermediate filament family, which acts as an internal scaffolding system inside cells. CK7’s presence or absence is specific to certain cell types, making its expression pattern a reliable biological signature. In medical diagnostics, particularly in oncology, mapping this signature helps classify tumors.
The Biology of Cytokeratin 7
CK7 is classified as a Type II intermediate filament protein (Keratin 7 or K7). Its primary function is to provide structural integrity and mechanical stability, particularly to epithelial cells, which line body surfaces, cavities, and glands. These filaments form complex networks in the cytoplasm, resisting physical stress and maintaining cell shape.
CK7’s structural role differs from other cellular components, such as actin filaments (involved in cell movement) or microtubules (aiding in cell division). Keratin proteins function as heterodimers, pairing with a Type I keratin to form the complete intermediate filament. This partnership ensures the robustness and resilience of the epithelial tissue layer.
Normal Distribution in the Body
CK7 expression is restricted to specific epithelial cells in healthy individuals, establishing a baseline for diagnostic comparisons. It is characteristically found in the simple epithelia lining glandular and ductal structures. Key sites of normal expression include:
- Breast ducts
- Lung
- Female reproductive tract (ovaries and fallopian tubes)
- Transitional epithelium (urothelium) lining the bladder and urinary tract
- Ducts of the pancreas and biliary system
- Thyroid gland
Conversely, CK7 is typically absent in the lower gastrointestinal tract (like the colon) and the prostate gland. Its presence or absence in these areas is highly significant in a medical context.
Diagnostic Role in Cancer Identification
CK7 is tested because many cancers retain the specific protein expression pattern of the original tissue from which they arose. Pathologists use immunohistochemistry (IHC) to detect CK7 in a tissue sample, usually from a biopsy. This technique applies specialized antibodies that bind to the CK7 protein, revealing its location and abundance through a visible color change under a microscope.
The test’s main purpose is to confirm if a tumor is a carcinoma (originating from epithelial cells), distinguishing it from other tumor types like sarcomas or melanomas. CK7 testing is frequently used to determine the primary site of a metastatic tumor whose origin is unknown. Analyzing the CK7 status helps pathologists narrow down the potential source of the cancer, which directly impacts treatment choice.
Interpreting CK7 and CK20 Patterns
CK7 is interpreted in conjunction with Cytokeratin 20 (CK20), another intermediate filament protein with a different, complementary tissue distribution pattern. The combined expression of these two markers creates four distinct patterns that help pathologists pinpoint the likely origin of a carcinoma.
CK7+/CK20-
The CK7-positive/CK20-negative profile is the most common pattern and strongly suggests a primary tumor from the lung, breast, endometrium, ovary, or thyroid. This pattern indicates an origin from simple glandular epithelia expressing CK7 but not CK20.
CK7-/CK20+
This pattern is highly characteristic of adenocarcinomas originating in the lower gastrointestinal tract, most notably the colon and rectum. This profile is also associated with Merkel cell carcinoma.
CK7+/CK20+
This pattern is less specific but commonly seen in transitional cell carcinomas of the urinary tract, mucinous ovarian carcinomas, and malignancies of the pancreas and stomach.
CK7-/CK20-
This pattern suggests an origin that expresses neither marker, such as renal cell carcinoma, hepatocellular carcinoma, or prostate adenocarcinoma.
While these patterns are powerful diagnostic tools, they are not absolute and must be interpreted alongside the patient’s clinical history and other specific tumor markers. The combination of CK7 and CK20 provides a crucial initial step in classifying metastatic cancer of unknown origin.