1. INTESTINAL DIFFERENTIATION IN PULMONARY ADENOCARCINOMA Paul Theunissen, MD, PhD, Nick van Rodijnen, Dept. of pathology, Atrium Medisch Centrum, Heerlen, Netherlands 1 Email: p.theunissen@atriummc.nl

2. INTRODUCTION In the literature only one case of pulmonary adenocarcinoma has been reported, in which the immunophenotype perfectly mimicked that of metastatic colorectal carcinoma (Am J Clin Pathol 2009;131:129-133). The purpose of this study is to evaluate the occurence of any intestinal differentiation in primary pulmonary adenocarcinomas, in order to investigate if overlapping immunohistochemical patterns with metastatic (colo)rectal carcinoma exist. 2

3. MATERIAL & METHODS (1) The paraffin blocks of the 50 most recent cases of resected pulmonary adenocarcinomas were taken from our archives, supplemented with 4 cases of resected colorectal carcinoma and 1 pulmonary metastasis of rectal carcinoma. From each block, 3 tumor core biopsies (1.5 mm) were taken using tissue microarray (TMA) technique and put in a TMA block. Immuno-histochemistry was performed on 2µm sections of the TMA blocks, with the DAKO automated stainer (Envision® polymer method). 3

4. antibodysourceclonedilutionepitope MUC2DAKOCCP58ready-to-useglycoprotein CDX2DAKODAK-CDX2ready-to-usehomeodomain transcription factor CK20DAKOKs20.8ready-to-usekeratin TTF1DAKO8G7G3/1ready-to-usethyroid transcription factor Napsin ANovocastraIP641 : 200aspartic proteinase MATERIAL & METHODS (2) 4

5. MATERIAL & METHODS (3) Cut-off points immunostaining (all antibodies): <10% tumor cells: negative 10-30% tumor cells:focal/weak positive >30% tumor cells:positive 5

6. 6 Results: pulmonary adenocarcinomas (n=50)

7. 7 Results: colorectal adenocarcinomas (n=5)

8. RESULTS: typical staining pattern pulmonary adenocarcinoma 8 TTF1napsinMUC2CDX2CK20

9. RESULTS: typical staining pattern of colorectal adenocarcinoma 9 TTF1napsinMUC2CK20CDX2

10. RESULTS: 3 different cases of pulmonary adenocarcinoma with focal expression of an intestinal marker 10 MUC2 CDX2 CK20

11. CONCLUSIONS 1.Expression of CDX2, MUC2 and CK20, indicating intestinal differentiation, is unusual in primary pulmonary adenocarcinoma, occurring in 8%, 6% and 2% respectively. When present, the expression is only focal and not diffuse. The vast majority of primary pulmonary adenocarcinomas express both TTF1 and napsine A, 90% and 86 % respectively. 2.Colorectal carcinomas (CRC) show strong and diffuse expression of intestinal markers CDX2 and CK20, whereas MUC2 is only focally present in most cases. CRC lack any expression of TTF1 and napsine A. 3.We found no overlap in immunohistochemical pattern between primary pulmonary adenocarcinoma and metastatic colorectal adenocarcinoma 11