Enhanced karyopherin-α2 expression is associated with carcinogenesis in patients with intraductal papillary mucinous neoplasms

Background/objectives: Intraductal papillary mucinous neoplasms (IPMN) can become malignant. Karyopherin-α2 (KPNA2) plays a central role in nucleocytoplasmic transport and is associated with various types of cancer. The current study examined pancreatic KPNA2 expression in cancer patients and evaluated its association with clinicopathological factors, cancer cell proliferation.

Methods: KPNA2 expression was investigated by immunohistochemistry in 40 surgically resected IPMN samples and its association with clinicopathological factors and Ki-67 expression were examined.

Results: Eighteen IPMN samples (45% of patients) showed positive KPNA2 expression. KPNA2 expression levels in IPMN tissue with invasive carcinoma were significantly higher than those in adjacent normal tissues and in IPMN tissue with low-to high-grade dysplasia. KPNA2 expression correlated with pathological malignancy and Ki-67 labeling index and KPNA2 and Ki-67 expression was co-localized in nuclei. E2F were co-localized with KPNA2 in the IPMN tissues with high expression of KPNA2. KPNA2 expression was enhanced in the invasion front and in proliferating Ki-67-positive cells. In addition, KPNA2 expression in IPMN tissues was associated with older age, dilation of main pancreatic duct diameter, the presence of nodules, and histological type.

Conclusion: KPNA2 expression is associated with carcinogenesis of IPMN through the adenoma-carcinoma sequence.