Predictive value of tumor proliferative indices in periampullary cancers: Ki-67, mitotic activity index (MI) and volume corrected mitotic index (M/V) using tissue microarrays

Abstract

BACKGROUND: Morphometry [nuclear Ki-67 labelling, mitotic activity index (MI), and volume-corrected mitotic index (M/V)] for periampullarycancers using tissue microarrays has not been performed previously. The purpose of the study was to assess these indices on tissue microarray (TMA) sections constructed from patients with periampullary cancers and study their association with clinicopathological variables. METHODS: Immunohistochemical staining for Ki-67 was performed on formalin-fixed pancreatic TMA sections. Expression of Ki-67 was assessed as the percentage of cancer cell nuclei expressing MIB1, MI as the mean percentage of Ki-67 from 10 random high-power fields, and M/V was calculated after standardizing MI for connective tissue volume and microscope parameters in the tumor using established protocols. RESULTS: Patients > or =70 years with periampullary cancers had higher Ki-67 expression (>15) compared with patients <70 years of age (chi(2) = 3.9, P = 0.047). Ki-67 expression was higher in tumors > or =2 cm (chi(2) = 4.9, P = 0.028) compared with smaller tumors. Higher MI (>15) was clearly associated with worsening histological grade (chi(2) = 9.2, P = 0.010). The median survival for tumors of the pancreaticobiliary subtype (pancreatic ductal adenocarcinoma and cholangiocarcinoma) was 43 months in the group with an M/V score of <20, compared with 18 months for the group with a score > or =20 (P = 0.001). There was no statistically significant difference in survival, based on M/V score, for tumors of the intestinal subtype (ampullary and duodenal adenocarcinoma). CONCLUSIONS: In periampullary cancers, Ki-67 and MI are proliferative indices predictive of tumor behavior. M/V was predictive of survival in tumors of the pancreaticobiliary subtype.