Cytokeratin AE1/AE3, IHC with Interpretation

This first-line screening test evaluates neoplasms of unknown origin and helps to determine a cell's epithelial lineage. This test is also routinely used in anatomic pathology to detect metastatic tumor cells in lymph node and bone marrow specimens [1].

Cytokeratin (CK) AE1/AE3 is a broad-spectrum immunohistochemical antibody cocktail that is used to identify the expression of high- and low-molecular weight keratins. Positive staining is generally indicated by filamentous cytoplasmic or membranous reactivity within the cells of interest and typically implies an epithelial origin [1].

CK AE1/AE3 generally reacts with well-differentiated epithelial neoplasms, with some notable exceptions. Neuroendocrine carcinomas, including small cell carcinomas, show variable reactivity with CK AE1/AE3. Small cell carcinomas, when immunoreactive, classically exhibit a perinuclear dot-like pattern of immunoreactivity with CK AE1/AE3 [1].

Hepatocellular carcinoma classically lacks reactivity with CK AE1/AE3. Likewise, adrenocortical neoplasms are often negative for CK AE1/AE3 and other immunohistochemical markers of epithelial origin. Renal cell carcinomas show variable immunoreactivity with CK AE1/AE3. Classic CK AE1/AE3 cocktails do not detect CK 9, CK 12, CK 17, and CK18 [1].

Note: Interpretation of CK AE1/AE3 staining requires knowledge of which cells within the tissue section or cell block represent cells of interest. Poorly differentiated carcinomas, as well as some other carcinomas, may lack expression of CK AE1/AE3. Likewise, CK AE1/AE3 has cross-reactivity with some non-epithelial cell types (eg, glioblastoma) [1].

The results of this test should be interpreted in the context of pertinent clinical and family history as well as physical examination findings.

Reference
⁠⁠⁠⁠⁠⁠⁠1. Rekhtman N, et al. Immunostains: Introduction. In: Rekhtman N, Baine MK, Bishop JA. Quick Reference Handbook for Surgical Pathologist. 2nd ed. Springer; 2019:3-21