Panels of immunohistochemical markers help determine primary sites of metastatic adenocarcinoma

Seog Yun Park, Baek Hee Kim, Jung Ho Kim, Sun Lee, Gyeong Hoon Kang

Research output: Contribution to journalArticlepeer-review

195 Citations (Scopus)


Context. - Although identification of the primary tumor in patients with metastatic adenocarcinoma has a profound clinical impact, diagnosing the organ of origin is frequently difficult. Because none of the individual immunohistochemical markers used for tissue identification are both site specific and site sensitive, multiple markers are needed to improve the prediction of primary sites. Objective. - To develop an effective approach to immunohistochemically evaluate metastatic adenocarcinoma for the assignment of a likely primary site of origin. Design. - Expression profiles of CDX2, cytokeratin (CK) 7, CK20, thyroid transcription factor 1 (TTF-1), carcinoembryonic antigen (CEA), MUC2, MUC5AC, SMAD4, estrogen receptor (ER), and gross cystic disease fluid protein 15 (GCDFP-15) were generated in adenocarcinomas from 7 primary sites, followed by construction of a decision tree and design of multiple-marker panels. Expression of these markers was evaluated immunohistochemically in 314 primary adenocarcinomas (50 cases each of colorectal, gastric, lung, pancreatic, bile duct, and breast, and 14 cases of ovarian origin) using the tissue array method. Results were validated using 60 cases of metastatic adenocarcinoma with known primaries. Results. - Organ-specific immunostaining profiles using multiple markers provided high sensitivity, specificity, and positive predictive value in detecting primary adenocarcinomas, as follows: colorectal, TTF-1-/CDX2 +/CK7-/CK20+ or TTF-1-/CDX2 +/CK7-/CK20-/(CEA+ or MUC2 +); ovarian, CK7+/MUC5AC+/TTF-1 -/CDX2-/CEA-/GCDFP-15-; breast, GCDFP-15+/TTF-1-/CDX2-/CK7+/ CK20- or ER+/TTF-1-/CDX2-/CK20 -/CEA-/MUC5AC-; lung, TTF-1+ or TTF-1-/CDX2-/CK7+/CK20-/GCDFP- 15-/ER-/CEA-/MUC5AC-; pancreaticobiliary, TTF-1-/CDX2-/CK7+/CEA +/MUC5AC+; and stomach, TTF-1-/CDX2 +/CK7+/CK20-. Overall, these combined phenotypes correctly predicted the tester samples (metastatic adenocarcinomas with known primaries) in 75% of cases. Conclusions. - Determination of tissue-specific immunostaining profiles is valuable in the diagnostic differentiation of metastatic adenocarcinomas from seven common primary sites and should help to correctly predict the organ of primary tumor origin.

Original languageEnglish
Pages (from-to)1561-1567
Number of pages7
JournalArchives of Pathology and Laboratory Medicine
Issue number10
Publication statusPublished - 2007 Oct
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medical Laboratory Technology


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