PAX8 Expression in Pancreatic Endocrine Tumors: Correlation with Pathologic Features and Behavior
KB Long, A Srivastava, MS Hirsch, JL Hornick. Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Dartmouth-Hitchcock Medical Center, Lebanon, NH
Background: PAX (paired box) genes encode a family of transcription factors that regulate organogenesis and cell-lineage specification in multiple organ systems. In the pancreas, PAX proteins play a critical role in islet cell differentiation. We recently observed that islet cells show strong, diffuse staining for PAX8. However, PAX8 expression has not been examined in pancreatic endocrine tumors (PETs). The purpose of this study was to evaluate PAX8 in PETs, and to correlate expression with clinical and pathologic features and behavior. PAX8 expression in other well-differentiated neuroendocrine tumors (WDNET) was also studied.
Design: In total, 149 tumors were evaluated: 63 PET and 28 ileal, 5 duodenal, 5 gastric, 19 appendiceal, 13 rectal, and 16 pulmonary carcinoid tumors. Immunohistochemistry was performed after pressure cooker antigen retrieval using a rabbit anti-PAX8 polyclonal antibody (Proteintech; 1:800). Nuclear staining in >5% of tumor cells was considered a positive result. Statistical analysis was performed using the Fisher exact or chi square test; all reported p values are two-tailed.
Results: In the normal pancreas, PAX8 expression was restricted to islet cells, with absence of staining in acinar and ductal epithelium. PAX8 was positive in 40/63 (63%) PET. Expression of PAX8 was significantly associated with WHO category 1.1 vs category 1.2 or 2 (positive in 94%, 58%, and 48%, respectively; p<0.05) and inversely correlated with the development of liver metastases (positive in 71% of localized tumors vs 41% with liver metastases; p<0.05). PAX8 expression was not associated with functional status or other pathologic features. PAX8 was detected in 1/5 (20%) gastric, 5/5 (100%) duodenal, 0/28 (0%) ileal, 4/19 (21%) appendiceal, 11/13 (85%) rectal, and 0/16 (0%) pulmonary carcinoid tumors.
Conclusions: PAX8 is expressed in normal pancreatic islet cells as well as in a high proportion of PETs. In the GI tract, PAX8 is positive in the majority of duodenal and rectal carcinoid tumors, and in a minor subset of appendiceal and gastric carcinoids. PAX8 expression is absent in ileal and pulmonary carcinoid tumors. These findings suggest that PAX8 may be helpful in determining primary site for a WDNET metastatic to the liver, since ileal (PAX8 negative) and pancreatic (PAX8 positive) tumors most often present as a metastasis from an occult primary. PAX8 may be a prognostic marker in PETs, since loss of expression is associated with malignant behavior.
Category: Liver & Pancreas
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 218, Tuesday Afternoon