NKX2.8 Expression in TTF-1 Negative and KRAS-Mutant Pulmonary Mucinous Adenocarcinoma Supports the Concept of a Biologically Distinct Category of Lung Adenocarcinoma
James Suh, Stephanie Krauter, Luis Chiriboga, Harvey Pass. NYU Langone Medical Center, New York, NY
Background: The 2011 IASLC/ATS/ERS multidisciplinary classification of lung adenocarcinoma defined the entity of invasive mucinous adenocarcinoma (formerly mucinous bronchioloalveolar carcinoma; IMA), which has approximately 76% 5-year disease-free survival in Stage I patients. IMA has been correlated with TTF-1/NKX2.1 negativity and KRAS mutation, suggesting that it is biologically distinct from non-mucinous lung adenocarcinoma (NMA). Our aim is to investigate whether immunohistochemical expression of NKX2.8, a lung developmental transcription factor and potential tumor suppressor, can be detected in IMA.
Design: 10 consecutive cases of surgically resected IMA and 10 non-consecutive cases of surgically resected NMA at one institution (2011-12) were reviewed. NMA cases were selected to include 2 adenocarcinoma in situ, 2 minimally invasive adenocarcinoma, 2 lepidic predominant adenocarcinoma and 1 each of acinar, papillary, micropapillary and solid predominant adenocarcinoma while blinded to tumor mutation status. Immunohistochemistry was performed on formalin-fixed paraffin-embedded tissue to evaluate expression of CK7, CK20, TTF-1, Napsin-A, CDX-2 and NKX2.8. Molecular mutation status was recorded for each case.
Results: IMA was positive for CK7 in 10/10 cases, CK20 in 4/10 cases, TTF-1 in 2/10 cases, Napsin-A in 3/10 cases, CDX-2 in 4/10 cases and NKX2.8 in 8/10 cases whereas NMA was positive for CK7 in 10/10 cases, CK20 in 0/10 cases, TTF-1 in 10/10 cases, Napsin-A in 10/10 cases, CDX-2 in 0/10 cases and NKX2.8 in 4/10 cases. The difference in the numbers of NKX2.8 positive cases between the two groups was not statistically significant (p-value = 0.1698), but NKX2.8 was positive in 7/8 cases of TTF-1 negative IMA. Five KRAS and zero EGFR mutations were identified in IMA whereas three KRAS and two EGFR mutations were identified in NMA. The difference in the numbers of KRAS-mutant cases between the two groups was not statistically significant (p-value = 0.6499), but NKX2.8 was positive in 4/5 cases of KRAS-mutant IMA. EML4-ALK translocation was not detected.
Conclusions: NKX2.8 expression is present in up to 88% of TTF-1 negative and 80% of KRAS-mutant pulmonary mucinous adenocarcinomas, providing further evidence that IMA is biologically distinct from NMA. Additional studies are needed to determine whether NKX2.8 can be used to distinguish IMA from metastatic adenocarcinomas of upper gastrointestinal tract and pancreatobiliary origin.
Monday, March 4, 2013 1:30 PM
Proffered Papers: Section D, Monday Afternoon