Prognostic significance of Wilms' tumor 1 expression in patients with pancreatic ductal adenocarcinoma

Abstract

The only current curative treatment for patients with pancreatic ductal adenocarcinoma (PDA) is surgical resection, and certain patients still succumb to disease shortly after complete surgical resection. Wilms' tumor 1 (WT1) serves an oncogenic role in various types of tumors; therefore, in the present study, WT1 protein expression in patients with PDA was analyzed and the association with overall survival (OS) and disease-free survival (DFS) time in patients with PDA was assessed following surgical resection. A total of 50 consecutive patients with PDA who received surgical resection between January 2005 and December 2015 at the Jikei University Kashiwa Hospital (Kashiwa, Chiba, Japan) were enrolled. WT1 protein expression in PDA tissue was measured using immunohistochemical staining. Furthermore, laboratory parameters were measured within 2 weeks of surgery, and systemic inflammatory response markers were evaluated. WT1 protein expression was detected in the nucleus and cytoplasm of all PDA cells and in tumor vessels. WT1 exhibited weak staining in the nuclei of all PDA cells; however, the cytoplasmic expression of WT1 levels was classified into four groups: Negative (n=0), weak (n=19), moderate (n=23) and strong (n=8). In patients with PDA, it was demonstrated that the OS and DFS times of patients with weak cytoplasmic WT1 expression were significantly prolonged compared with those of patients with moderate-to-strong cytoplasmic WT1 expression, as determined by log-rank test (P=0.0005 and P=0.0001, respectively). Furthermore, an association between the density of WT1-expressing tumor vessels and worse OS/DFS times was detected. Multivariate analysis also indicated a significant association between the overexpression of WT1 in PDA tissue and worse OS/DFS times. To the best of our knowledge, the present study is the first to demonstrate that moderate-to-strong overexpression of WT1 in the cytoplasm of PDA cells is significantly associated with worse OS/DFS times. Therefore, overexpression of WT1 in the cytoplasm of PDA cells may impact the recurrence and prognosis of patients with PDA following surgical resection. The results further support the development of WT1-targeted therapies to prolong survival in all patients with PDA.

An unusual case report of metastatic periampullary carcinoma

“…Kanai T et al, found in their study that the median DFS time for patients with PDA with weak and moderate to strong cytoplasmic WT1 expression was 543 and 196 days, respectively. 6 The differential diagnosis between primary mucinous epithelial ovarian cancers and mucinous metastasis from other organs also relies on other clinical characteristics including bilaterality, surface involvement, signet ring cell presence, and lympho vascular invasion, which are more common in metastases and quite rare in primary mucinous ovarian cancers. 3,4 There is still a certain proportion of tumors for which, based on the morphological and immunohistochemical (IHC) features alone, the distinction between a primary and a metastatic tumor is not possible.…”

Quantitative proteomics identifies brain acid soluble protein 1 (BASP1) as a prognostic biomarker candidate in pancreatic cancer tissue

“…Few studies have studied expression patterns of WT1 in pancreatic cancer [46,47]. However, only one recent study evaluated the prognostic value of WT1 in pancreatic ductal adenocarcinoma, indicating that cytoplasmic overexpression of WT1 correlated with unfavourable prognosis for the patient [48]. Notwithstanding, these findings were based on a small cohort of only 50 patients and additional studies would be necessary to confirm these results.…”

Reader‑free ELISPOT assay for immuno‑monitoring in peptide‑based cancer vaccine immunotherapy

“…The Wilms' tumor 1 (WT1) gene was originally isolated as a gene responsible for pediatric kidney neoplasm and had been regarded as a tumor suppressor gene (18). However, a number of researchers consider the WT1 gene to serve an oncogenic role in leukemia (19)(20)(21)(22) and a wide variety of solid tumors (23)(24)(25) based on the results reported by our group and other groups (26)(27)(28). The WT1 protein is highly immunogenic (29).…”