Comparison of PAX6 and PAX8 as Markers for Pancreatic Neuroendocrine Tumors (NETs)
Jin-Ping Lai, Jamie Koo, Fai Chung, Allen B Mendez, Melissa Kahn, Richard Mertens, Deepti Dhall. Cedars-Sinai Medical Center, Los Angeles, CA
Background: Our previous study showed that PAX8 helps in distinguishing pancreatic NETs from ileal NETs. More recently it has been suggested that immunoreactivity of pancreatic NETs for PAX8 is due to cross reactivity of the PAX8 antibody with PAX6, a transcription factor and differentiation marker of neuroendocrine cells. The aim of this study was to compare the sensitivity and specificity of PAX6 and PAX8 for pancreatic NETs.
Design: PAX6 expression was investigated in 92 NETs, each of which had been previously stained for PAX8 in our prior study. Seventy-one primary NETs from different sites (22 pancreatic, 21 ileal, 12 pulmonary, 6 gastric and 10 rectal) and 21 metastatic pancreatic NETs were studied. Tumors showing moderate to strong nuclear staining of at least 5% of cells or tumors showing weak nuclear staining of at least 10% of cells were considered positive.
Results: Among primary NETs, PAX6 was positive in 68% (15/22) of pancreatic, 0% (0/21) of ileal, 0% (0/12) of pulmonary, 0% (0/6) of gastric and 90% (9/10) of rectal NETs. Forty-three percent (9/21) of metastatic pancreatic NETs in liver were positive for PAX6, all of which showed diffuse, moderate to strong staining. In comparison with surrounding islets (n =15), the staining intensity for PAX6 was found to be decreased in 64% of the primary pancreatic NETs. Moderate to strong expression of PAX6 was noted in 10 of 13 low grade primary pancreatic NETs but in only 2 of 9 intermediate grade primary pancreatic NETs (p=0.027). The comparison of staining of NETs for PAX6 and PAX8 is displayed in Table 1. The sensitivity and specificity for pancreatic NETs were 56% and 82% for PAX6 and 67% and 73% for PAX8, respectively.
|Primary pancreatic||Metastatic pancreatic||Primary ileum||Primary lung||Primary stomach||Primary rectum|
|PAX6||15/22 (68%)||9/21 (43%)||0/21||0/12||0/6||9/10 (90%)|
|PAX8||18/22 (82%)||11/21 (52%)||0/21||3/12 (25%)||2/6 (33%)||8/10 (80%)|