Research Papers: Pathology:

LEF1, TFE3, and AR are putative diagnostic markers of solid pseudopapillary neoplasms

Eun Kyung Kim _, Mi Jang, Minhee Park and Hoguen Kim

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Oncotarget. 2017; 8:93404-93413. https://doi.org/10.18632/oncotarget.21854

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Eun Kyung Kim1, Mi Jang1, Minhee Park2 and Hoguen Kim1,2,3

1 Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea

2 Departments of Pathology and Brain, Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea

3 Healthcare Review and Assessment Committee, Health Insurance Review & Assessment Service, Seoul, Republic of Korea

Correspondence to:

Hoguen Kim, email: [email protected]

Keywords: solid pseudopapillary neoplasm; lymphoid enhancer-binding factor 1; transcription factor for immunoglobulin heavy-chain enhancer 3; androgen receptor; Ki-67; Pathology Section

Received: July 27, 2017 Accepted: September 23, 2017 Published: October 16, 2017


The diagnosis of solid pseudopapillary neoplasms (SPNs) is challenging because some SPNs share many similar morphological and immunohistochemical features with other pancreatic neoplasms. In this study, we investigated potential diagnostic markers of SPN.

Based on the SPN-specific upregulated genes from a previous DNA microarray and proteome study, we selected six immunohistochemical markers [beta-catenin, androgen receptor (AR), lymphoid enhancer-binding factor 1 (LEF1), transcription factor for immunoglobulin heavy-chain enhancer 3 (TFE3), fused in sarcoma (FUS), and WNT inhibitory factor 1 (WIF-1)]. We also evaluated the Ki-67 proliferative index to investigate its associations with prognosis. To validate these markers, we studied 91 SPNs as well as 51 pancreatic ductal carcinomas (PDC) and 48 neuroendocrine tumors (NET) as controls.

We found frequent and diffuse nuclear expressions of β-catenin (98.9%), AR (81.3%), LEF1 (93.4%), TFE3 (74.7%), FUS (84.6%), and cytoplasmic expression of WIF-1 (96.7%) in SPNs. In contrast, PDCs and NETs showed no expression. (P < 0.001). When beta-catenin, LEF1, and TFE3 staining were combined, the sensitivity and specificity were 100% and 91.9%, respectively. Four (4.4%) SPNs showed distant metastasis and these tumors were associated with a relatively high Ki-67 proliferative index (≥ 5%; P = 0.013).

We identified LEF1, TFE3, and AR as putative diagnostic markers of SPN, auxiliary to β-catenin. Incorporated into an immunohistochemical panel, these markers could be beneficial to distinguish SPN from PDC and NET. In addition, we suggest that the Ki-67 proliferative index can be a predictive marker of metastasis in SPNs.

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