Adenocarcinomas metastatic to the liver: the value of cytokeratins 20 and 7 in the search for unknown primary tumors

Cancer. 1999 Jan 1;85(1):171-7. doi: 10.1002/(SICI)1097-0142(19990101)85:1<171::AID-CNCR24>3.0.CO;2-V.


Background: Metastatic adenocarcinoma in the liver with an unidentified primary tumor site is a common clinical problem. Pathologists often are asked to identify the primary tumor site. The histologic picture itself usually is not helpful, because the histology may be similar in the metastases of tumors with different primary localizations. Immunohistochemistry can be helpful, but the previously recommended antibody panels are too complicated for everyday use.

Methods: A simple immunohistochemical algorithm with two monoclonal cytokeratin (CK) antibodies, CK20 and CK7, was tested on 93 autopsy cases of adenocarcinomas metastatic to the liver. Sections of the liver metastases were stained automatically and evaluated as negative (no staining), focally positive, or diffusely positive. Statistical comparison of the staining results for a single antibody was calculated as an odds ratio.

Results: Thirty-six of 93 (39%) metastases proved to be CK20 positive (+). In this group, the CK20+/CK7 negative (-) pattern was highly characteristic for colorectal localization of the primary tumor, having been observed 17 of 21 of the cases (81%). The CK20+/CK7+ pattern of the metastatic liver adenocarcinomas was highly suggestive of primary localization in the pancreas or biliary tract (11 of 14 cases; 79%). Exclusion of the tumors originating in the stomach raised these values to 94% and 92%, respectively. The statistically calculated predicted probability of primary tumor site being in the colon or rectum for CK20+/CK7- metastasis was 78,41%, the probability of a primary tumor being located in the pancreas or biliary tract was 74,85%, if calculated for the whole study group.

Conclusions: The tested simple algorithm proved to be useful in CK20 positive (+) cases, predicting a primary tumor localization in the colon, rectum, pancreas, or biliary tract with high accuracy. The CK20- group was too heterogeneous to be classified adequately by these two antibodies.

MeSH terms

  • Adenocarcinoma / secondary*
  • Algorithms
  • Colorectal Neoplasms / pathology
  • Female
  • Gallbladder Neoplasms / pathology
  • Humans
  • Immunohistochemistry
  • Intermediate Filament Proteins / analysis*
  • Keratin-20
  • Keratin-7
  • Keratins / analysis*
  • Liver Neoplasms / secondary*
  • Male
  • Neoplasms, Unknown Primary / diagnosis*
  • Pancreatic Neoplasms / pathology
  • Retrospective Studies
  • Stomach Neoplasms / pathology


  • Intermediate Filament Proteins
  • KRT20 protein, human
  • KRT7 protein, human
  • Keratin-20
  • Keratin-7
  • Keratins