From the Guidelines
A CK7-positive and CK20-negative staining pattern typically suggests a tumor of epithelial origin from specific anatomical sites, most commonly the lung, breast, ovary, endometrium, thyroid, salivary gland, or pancreaticobiliary tract. This immunohistochemical profile is particularly useful in diagnosing and determining the primary site of metastatic carcinomas. When pathologists encounter a tumor of unknown origin, this staining pattern helps narrow down the differential diagnosis by excluding tumors that typically express CK20, such as colorectal adenocarcinomas, Merkel cell carcinomas, and most urothelial carcinomas. The biological basis for this pattern relates to the differential expression of cytokeratin proteins in various epithelial tissues during development. CK7 is a 54 kDa basic protein found in glandular and transitional epithelia, while CK20 is a 46 kDa acidic protein expressed in gastrointestinal epithelia, urothelium, and Merkel cells. This staining result should always be interpreted in conjunction with clinical information, morphological features, and additional immunohistochemical markers to establish a definitive diagnosis, as suggested by 1. Some key points to consider in the differential diagnosis include:
- The presence of TTF-1, which is often positive in lung and thyroid cancers, as noted in 2.
- The presence of ER, PR, and GCDFP-15, which are often positive in breast cancer, as noted in 3.
- The presence of CK19, which is often positive in pancreatic and biliary tract cancers, as noted in 3. It is essential to consider these factors and interpret the staining result in the context of the overall clinical picture to establish an accurate diagnosis, as emphasized in 4.
From the Research
Cytokeratin 7 and 20 Expression
- A stain that is positive for CK7 and negative for CK20 can be indicative of a primary lung adenocarcinoma, as studies have shown that this CK7+/CK20- phenotype is more commonly associated with lung cancer 5, 6.
- This expression pattern can also be seen in other types of adenocarcinomas, such as those originating from the breast or ovary, but is less common in colorectal adenocarcinomas 7, 8.
- The CK7+/CK20- phenotype is not specific to lung cancer and can be seen in other types of tumors, therefore, a combination of immunohistochemical markers, including TTF-1, CK7, and CK20, is often used to increase the accuracy of diagnosis 6.
Diagnostic Considerations
- The use of CK7 and CK20 expression patterns can be helpful in determining the origin of metastatic adenocarcinomas of unknown primary site 7, 5.
- However, the interpretation of these results should be done in conjunction with other clinical and pathological findings, as the expression patterns can vary between different types of tumors and even within the same tumor type 8, 9.
- The CK7+/CK20- phenotype has been associated with a higher frequency of metastases to the lung, liver, and other organs, and may be indicative of a more aggressive tumor behavior 5, 9.