Solitary cell infiltration is a novel indicator of poor prognosis and epithelial-mesenchymal transition in pancreatic cancer

Pancreatic cancer is one of the most aggressive and lethal human malignancies in the Western world. A wide variety of intratumor glandular differentiation, including solitary infiltrating cancer cells, is a prominent microscopic finding in pancreatic cancer. We reviewed 114 resected cases of pancreatic ductal adenocarcinoma to investigate the prognostic impact of the degree of solitary cell infiltration, defined by the number of solitary infiltrating cancer cells. The clinicopathologic correlation of solitary cell infiltration was further evaluated. Seventy-six (67%) cases showed 7 or more solitary infiltrating cancer cells in 10 high-power fields and were labeled as having a high degree of solitary cell infiltration. A high degree of solitary cell infiltration correlated significantly with poor overall survival, the grade, lymphatic invasion, and lymph node metastasis. Multivariate analysis revealed that the degree of solitary cell infiltration, the grade, and the margin status were independent prognostic factors. Grade 1 and 2 tumors with a high degree of solitary cell infiltration, compared with low infiltration, correlated significantly with poor overall survival. Grade 3 tumors showed a worse overall survival than grade 1 and 2 tumors with either a high or a low degree of solitary cell infiltration. Immunohistochemical analysis showed that a high degree of solitary cell infiltration correlated with reduced E-cadherin and increased vimentin expression. In conclusion, solitary cell infiltration is a significant prognostic indicator and serves as a morphological clue to epithelial-mesenchymal transition in pancreatic cancer.