TTF-1 and Napsin-A Are Expressed in a Subset of Cholangiocarcinomas Arising from the Gallbladder and Hepatic Ducts: Continued Caveats for Utilization of Immunohistochemisry Panels
Lea F Surrey, Renee Frank, Paul J Zhang, Emma E Furth. Hospital of the University of Pennsylvania, Philadelphia, PA
Background: Thyroid transcription factor-1 (TTF-1) and Napsin-A (NapA) are frequently used to classify a tumor of unknown origin as lung primary. Multiple studies have shown that TTF-1 positivity can occasionally occur in adenocarcinoma of non-pulmonary origin with different antibody clones. Currently, TTF-1 has been reported as negative or infrequently positive in tumors of biliary origin. Based on an index case of cholangiocarcinoma (cholangioCA) expressing TTF-1, we were prompted to study TTF-1 and NapA positivity in a cohort of cholangioCA.
Design: Archived paraffin embedded tissue blocks from liver, gallbladder, and pancreato-biliary resections from 2005-2012 were chosen for cholangioCA (n=33) and non-neoplastic intra- and extra-hepatic biliary epithelium (NNBE) control tissue (n=26). Immunohistochemistry for TTF-1 (SPT24 clone) and NapA (KCG1.1 clone) was performed. TTF-1 nuclear staining was graded for intensity on a scale of 0 to 3 (with 2+ and 3+ considered positive). The quantity of positive tumor was scored as follows: 0= 0%, 1=1-30%, 2=31-66%, or 3=67-100%. For NapA diffuse granular cytoplasmic staining was considered positive. Statistical analysis was performed using the two-sided Fischer exact test.
Results: TTF-1 was negative in NNBE but positive in 24.2% of cholangioCA. Interestingly, all TTF-1 positive cases (n=8) were extrahepatic (n=19, p=0.01) and arose from the upper biliary tract (gallbladder and hepatic ducts, n=13). TTF-1 positivity was associated with age ≥60 (p=0.01) but was not associated with gender (p=0.43). Among positive TTF-1 cases, the average intensity and quantity score was 2.9 and 1.9, respectively. The expression was not uniform in a tumor and showed patches of positivity. Three TTF-1 positive cases were also NapA positive (9% of total). NapA staining showed non-specific apical granular staining in 7 cholangioCA (21.8%).
Conclusions: In summary, 42.1% of extrahepatic cholangioCA expressed TTF-1, 37.5% of which also co-expressed NapA. No TTF-1 reactivity was detected in any NNBE. TTF-1 reactivity was more common in patients ≥60 years of age (47%). CholangioCA should be considered in the differential when evaluating a TTF-1 positive tumor of unknown primary, especially when using the SPT24 clone. As TTF-1 is not known for biliary system development and not detected in NNBE, the biologic significance of this “pulmonary” phenotype (TTF-1 and NapA expression) in a subset of cholangioCA is unknown and needs further investigation.
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 262, Monday Morning