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GATA3 is a transcription factor involved in the development and differentiation of lymphocytes, breast, and hair follicles. The protein is a useful immunohistochemical (IHC) marker for supporting diagnoses of breast or urothelial carcinoma. This can be especially helpful in metastatic neoplasms to help delineate site of origin. GATA3 is also reportedly positive in a percentage of pancreatic ductal adenocarcinomas (PDACs) and cholangiocarcinomas (CCs), but no study has closely evaluated this relationship with respect to clininopathologic features or patient outcome. Using tissue microarrays, we analyzed 240 PDACs and 60 CCs with GATA3 IHC and compared expression to various clinical and pathologic parameters. Overall, GATA3 positivity was seen in 16% of PDACs and 5% of CCs. GATA3 positivity in PDAC cases was more common in male patients (P=0.013). GATA3-positive PDACs trended toward worse survival on multivariate analysis (P=0.074). The only 3 GATA3-positive CCs were poorly differentiated (P=0.069); low case number precluded multivariate survival analysis for CCs. GATA3 positivity can occur in carcinomas of the pancreatobiliary system, which should be considered during IHC workup of neoplasms of unclear origin. This positivity seems to have minimal relevance to patient outcome.

Insulin-like growth factor-II messenger RNA-binding protein-3 (IMP3), is an oncofetal protein whose aberrant expression has previously been detected in multiple malignant neoplasms. Pulmonary neuroendocrine carcinomas demonstrate increased expression compared with pulmonary carcinoid tumors, but this relationship has not been studied in gastrointestinal neuroendocrine tumors (GINETs). This study examined IMP3 expression in GINETs, with a focus on correlation with established grading criteria. Fifty-four GINETs were immunohistochemically studied using a monoclonal antibody against IMP3. Using established World Health Organization criteria, the cases were stratified by grade and included 31 grade 1 neuroendocrine tumors (G1 GINETs), 15 grade 2 neuroendocrine tumors (G2 GINETs), and 8 neuroendocrine carcinomas (GINECs). The majority (51/54, 94.4%) of GINETs demonstrated IMP3 staining. Thirty cases (55.6%) showed IMP3 cytoplasmic/membranous staining in 60% or greater of tumor cells, with moderate to strong staining in nearly all of these cases (29/30; 96.7%). Of the remaining 24 cases, 3 cases showed no staining, whereas 17 (81%) demonstrated weak staining. When stratified by grade, there was no statistically significant difference in IMP3 staining among the 3 grades of GINETs; of the G1 GINETs, 14 (45.2%) demonstrated staining in at least 60% of tumor cells, compared with 10 (66.7%) G2 GINETs and 6 (75%) GINECs. Hindgut neoplasms of any grade were the most likely to show significant IMP3 staining. Unlike what has been demonstrated in neuroendocrine neoplasms in the lungs, GINETs appear to have a consistent IMP3 expression profile among all tumors grades, which may be reflective of their unique tumor biology.