PROLIFERATIVE ACTIVITY IN PANCREATIC ENDOCRINE TUMORS - ASSOCIATION WITH FUNCTION, METASTASES, AND SURVIVAL

Endocrine tumors of the pancreas are slow-growing lesions, yet one-thi rd to one-half will metastasize. It is generally accepted that histopa thologic features do not reliably predict metastatic potential or outc ome. We investigated whether proliferative activity, as determined by MIB-1 labeling, correlated with tumor type, metastasis, or patient sur vival. Formalin-fixed sections of pancreatic endocrine tumors were imm unohistochemically stained for the MIB-1 antibody against Ki-67 using the avidin-biotin complex technique. Labeling index (LI) was determine d by counting 1000 consecutive tumor cells in an area of greatest stai ning intensity at x400 and expressed as a percentage. The study group included 37 patients, including 10 gastrinomas, 9 insulinomas, 4 gluca gonomas, 2 VIPomas, and 12 nonfunctioning tumors. Twenty-one patients had metastases, primarily to regional lymph nodes and the liver. Five patients had MEN I. MIB-1 LI was significantly greater in the nonfunct ioning tumors (mean 20.9%) than in the functioning tumors (mean 5.1%) (p = 0.01). LI for functional tumors (insulinomas 6.4%, glucagonoma 4. 4%, gastrinomas 3.2%, VIPomas 3.2%) were similar to each other. MIB-1 was significantly higher in those tumors that metastasized (mean 15.6% ) compared to those that did not (mean 3.1%), (p = 0.04). All tumors w ith MIB-1 LI greater than or equal to 10% developed metastases. Logist ic regression showed that MIB-1 was a significant predictor of metasta ses (p = 0.003) after adjusting for functional status. MIB-1 LI also c orrelated with outcome in that those patients with MIB-1 LI greater th an or equal to 10% had a mean survival of 19 mo compared to 72 mo for those with levels <10% (p = 0.0001). Results of the proportional hazar ds model showed that MIB-1 remained a significant (p = 0.03) and indep endent predictor of survival times after adjustment for tumor size and functional status. Higher MIB-1 LI values were significantly associat ed with shorter survival times. In conclusion, MIB-1 LI appears to be a useful indicator of metastatic potential and is predictive of outcom e in PET.