AIM: To study the prognostic value of adjuvant chemotherapy in patients with pancreatic, ductal adenocarcinoma.METHODS: Lymph nodes from 106 patients with resectable pancreatic ductal adenocarcinoma were systematically sampled. A total of 318 lymph nodes classified histopathologically as tumor-free were examined using sensitive immunohistochemical assays.Forty-three (41%) of the 106 patients were staged as pT1/2, 63 (59%) as pT3/4, 51 (48%) as pN0, and 55 (52%)as pN1. The study population included 59 (56%) patients exhibiting G1/2, and 47 (44%) patients with G3 tumors.Patients received no adjuvant chemo- or radiation therapy and were followed up for a median of 12 (range:3.5 to 139) mo.RESULTS: Immunostaining with Ber-EP4 revealed nodal microinvolvement in lymph nodes classified as tumor free by conventional histopathology in 73(69%) out of the 106 patients. Twenty-nine (57%)of 51 patients staged histopathologically as pN0 had nodal microinvolvement. The five-year survival probability for pN0-patients was 54% for those without nodal microinvolvement and 0% for those with nodal microinvolvement. Cox-regression modeling revealed the independent prognostic effect of nodal microinvolvement on recurrence-free (relative risk 2.92,P=0.005) and overall (relative risk 2.49, P=0.009) survival.CONCLUSION: The study reveals strong and independent prognostic significance of nodal microinvolvement in patients with pancreatic ductal adenocarcinoma who have received no adjuvant therapy. The addition of immunohistochemical findings to histopathology reports may help to improve risk stratification of patients with pancreatic cancer.