Proliferative activity in pancreatic endocrine tumors: Association with function, metastases, and survival
- 64 Downloads
Endocrine tumors of the pancreas are slow-growing lesions, yet one-third to one-half will metastasize. It is generally accepted that histopathologic features do not reliably predict metastatic potential or outcome. We investigated whether proliferative activity, as determined by MIB-1 labeling, correlated with tumor type, metastasis, or patient survival. Formalin-fixed sections of pancreatic endocrine tumors were immunohistochemically stained for the MIB-1 antibody against Ki-67 using the avidin-biotin complex technique. Labeling index (LI) was determined by counting 1000 consecutive tumor cells in an area of greatest staining intensity at ×400 and expressed as a percentage. The study group included 37 patients, including 10 gastrinomas, 9 insulinomas, 4 glucagonomas, 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 nonfunctioning 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 with MIB-1 LI≥10% developed metastases. Logistic regression showed that MIB-1 was a significant predictor of metastases (p = 0.003) after adjusting for functional status. MIB-1 LI also correlated with outcome in that those patients with MIB-1 LI ≥10% had a mean survival of 19 mo compared to 72 mo for those with levels <10% (p = 0.0001). Results of the proportional hazards model showed that MIB-1 remained a significant (p = 0.03) and independent predictor of survival times after adjustment for tumor size and functional status. Higher MIB-1 LI values, were significantly associated with shorter survival times. In conclusion, MIB-1 LI appears to be a useful indicator of metastatic potential and is predictive of outcome in PET.
Key WordsPancreatic endocrine tumor MIB-1 proliferation prognosis survival metastases
Unable to display preview. Download preview PDF.
- 3.Heitz PhU, Kloppel G. Endocrine tumors of the pancreas and duodenum. Verh Dtch Ges Pathol 71:202–221, 1987.Google Scholar
- 4.Kloppel G, Delling G, Knipper A, Heitz PU. Immunocytochemical mapping of pancreatic apudomas in multiple endocrine adenomatosis with primary hyperparathyroidism. Acta Endocrinol 87(Suppl 215):57,58, 1978.Google Scholar
- 5.Eckhauser FE, Cheung PS, Vinik AI, Strodel WE, Lloyd RV, Thompson NW. Nonfunctioning malignant neuroendocrine tumors of the pancreas. Surg 100:978–987, 1986.Google Scholar
- 7.Compton CC. Diseases of the pancreas. In Weidner N., ed. The difficult diagnosis in surgical pathology. Philadelphia: Saunders, 1996;270–272.Google Scholar
- 11.Viale G, Doglioni C, Gamgacorta M, Zamboni G, Coggi G, Bordi C. Progesterone receptor immunoreactivity in pancreatic endocrine tumors. An immunocytochemical study of 156 neuroendocrine tumors of the pancreas, gastrointestinal and respiratory tracts, and skin. Cancer 70:2268–2277, 1992.PubMedCrossRefGoogle Scholar
- 12.Hofler H, Ruhri C, Putz B, Wirnsberger G, Hauser H. Oncogene expression in endocrine pancreatic tumors. Virchows Arch B Cell Pathol 55:355–361, 1988.Google Scholar
- 17.Pelosi G, Zamboni G, Doglioni C, Rodella S, Bresaola E, Iacono C, Serio G, Iannucci A, Scarpa A. Immunodetection of proliferating cell nuclear antigen assesses the growth fraction and predicts malignant in endocrine tumors of the pancreas. Am J Surg Pathol 16:1215–1225, 1992.PubMedCrossRefGoogle Scholar
- 23.Pinder SE, Wencyk P, Sibbering DM, Bell JA, Elston CW, Nicholson R, Robertson JFR, Blamey RW, Ellis IO. Assessment of the new proliferation marker MIB1 in breast carcinoma using image analysis: associations with other prognostic factors and survival. Br J Cancer 71:146–149, 1995.PubMedGoogle Scholar
- 26.Clarke MR, Weyant RJ, Watson CG, Carty SE. MIB-1, bcl-2, cathepsin B, cathepsin D, FGF, c-met and type IV collagenase in benign and malignant pheochromocytomas. Mod Pathol 9:47A, 1996.Google Scholar