The grade of pancreatic ductal carcinoma is an independent prognostic factor and is superior to the immunohistochemical assessment of proliferation

Tumour grade is one of the prognostic factors in pancreatic ductal adenocar cinoma, but its value is controversial. In this study, the predictive value and the reproducibility of the WHO grading system were reconsidered and th e possibility of supplementing it with the immunohistochemically assessed p roliferative activity was investigated. Seventy resected ductal adenocarcin omas of the head of the pancreas were evaluated. A total of 60 HPF fields o n two to four sections per tumour were screened for glandular differentiati on, mucin production, mitosis, and nuclear atypia by two observers with dif ferent degrees of experience. Each criterion was scored and the grade was c alculated from the mean value of all single scores. Corresponding slides we re immunohistochemically stained with the proliferation marker Ki-S5. The p ercentage of positive nuclei was assessed and a proliferation index (PI) as signed (<10% = 1; 20-50% = 2; >50% = 3). Multivariate analysis (Cox regress ion) identified grade and R stage as the most significant factors for predi cting survival. The PI determined on the basis of Ki-SS staining did not pr ove to be an independent prognostic factor. In 30 of 70 carcinomas, it corr elated with the tumour grade. Within a given tumour grade, the cases with t he least favourable prognosis could be distinguished on the basis of their PI. The inter-observer variability was considerable, with the main differen ces occurring in the group of G1 rumours. According to the refined WHO crit eria, the histopathological grade of pancreatic ductal carcinoma is an impo rtant independent prognostic factor, but reproducibility depends on the exp ertise of the observer. Criteria that relate to cellular and structural dif ferentiation seem to be more predictive than those related to proliferation . Copyright (C) 2000 John Wiley & Sons, Ltd.