Differential Immunoexpression Profiles in Appendiceal Mucinous Neoplasm

초록

Background: There has been a lot of debate on appendiceal mucinous neoplasm. Recently, appendiceal mucinous neoplasm of uncertain malignant potential (UMP) has been introduced. UMP is defined as follows; appendiceal mucinous neoplasm of bland cytoarchitecture, showing (1) epithelium deeply into underlying tissue, or (2) cystic gland-like structure in wall, or (3) uncertainity of complete excision, in the condition of loss of musularis mucosae and unclear invasion. The present study shows that characteristic protein expression profiling would be helpful to classify appendiceal mucinous tumor. Design: Total 70 cases of appendiceal mucinous neoplasm were histologically classified into three groups; 34 mucinous adenoma (BENIGN), 21 UMP, and 15 mucinous adenocarcinoma (MALIGNANT). MALGINANT contained appendiceal mucinous neoplasm with low grade cytoarchitectural atypia (so-called low grade malignant potential) and high grade atypia. Iimmunohistochemistry was performed for 24 antibodies; oncogenic function proteins (bcl-2, beta-catenin, CEA, C-erbB2, c-kit, Cox2, Cyclin D1, EGFR, Ki 67, NF-kappaB, VEGF), tumor suppressors (E-cadherin, FHIT, hMLH1, p53, p63, smad4), cell cycle regulators (p21, p27, p16) and mucin proteins (MUC1, MUC2, MUC5AC, MUC6). As controls, 32 non-neoplastic appendiceal tissues were included. Results: Among 24 examined proteins, nine proteins were more frequently altered in MALIGNANT than BENIGN (p < 0.05); beta-catenin (10% in BENIGN vs. 47% in MALIGNANT), CyclinD1 (43% vs. 93%), NF-kappaB (13% vs. 60%), VEGF (15% vs. 53%), E-cadherin (0% vs. 33%), p53 (9% vs. 47%), MUC2 (58% vs. 100%), MUC5AC (23% vs. 93%), and high Ki-67 labeling (31% vs. 67%). The expression profiles of these nine proteins in UMP were put in the middle of BENIGN and MALIGNANT. Accordingly, immunoexpression profiles of UMP were distinct from those of BENIGN or MALIGNANT (p < 0.05). Besides, BENIGN, UMP and MALIGNANT were different in the number of aberrant proteins (p < 0.05); mean 2.06 vs. 3.78 vs. 5.27 out of nine proteins, respectively. Conclusions: Appendiceal mucinous neoplasm can be classified into three groups, and mucinous neoplasm of uncertain malignant potential is a distinct entity in terms of molecular markers. Immunoexpression profiling may be useful to predict the clinicopathogical behavior of UMP.