TTF-1 and napsin A do not differentiate metastatic lung adenocarcinomas from primary esophageal adenocarcinomas: proposal of a novel staining panel.

Context: When adenocarcinomas arise within the esophagus, particularly when located away from the gastroesophageal junction, it may be important in some patients to differentiate between a primary esophageal adenocarcinoma and metastasis from another site. Lung adenocarcinoma is one tumor that has been reported to frequently metastasize to the esophagus.

Objectives: To create a panel of immunohistochemical markers that can reliably distinguish between an esophageal and pulmonary primary; within the gastrointestinal pathology literature, including published articles and textbooks, common lung immunohistochemical markers, such as TTF-1, are assumed to be negative in esophageal adenocarcinoma, yet, to our knowledge, no study has yet investigated the veracity of that presumption.

Design: In this study, 24 cases each of pulmonary and esophageal adenocarcinomas were stained with TTF-1, napsin A, CDX2, 34βE12, N-cadherin, and IMP3 in an attempt to define an optimal panel for differentiation. Esophageal adenocarcinomas occurring at the gastroesophageal junction were excluded in this study because a gastric primary tumor cannot be excluded in those cases.

Results: Surprisingly, TTF-1 and napsin A were positive in similar proportions of tumors from both sites. Those markers that differentiated statistically between esophageal and pulmonary adenocarcinoma were IMP3, CDX2, and N-cadherin.

Conclusions: When differentiating the origin of a tumor as either esophageal or pulmonary, an immunohistochemical panel consisting of IMP3, CDX2, and N-cadherin is superior to either TTF-1 or napsin A.