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

Eunkyung Kim, Mi Jang, Minhee Park, Hoguen Kim

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)93404-93413
Number of pages10
JournalOncotarget
Volume8
Issue number55
DOIs
Publication statusPublished - 2017 Nov 1

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Lymphoid Enhancer-Binding Factor 1
Androgen Receptors
Neoplasms
Pancreatic Ductal Carcinoma
Catenins
Neuroendocrine Tumors
beta Catenin
Sarcoma
Neoplasm Metastasis
Immunoglobulin Heavy Chains
Proteome
Oligonucleotide Array Sequence Analysis
Pancreatic Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Kim, Eunkyung ; Jang, Mi ; Park, Minhee ; Kim, Hoguen. / LEF1, TFE3, and AR are putative diagnostic markers of solid pseudopapillary neoplasms. In: Oncotarget. 2017 ; Vol. 8, No. 55. pp. 93404-93413.
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abstract = "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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LEF1, TFE3, and AR are putative diagnostic markers of solid pseudopapillary neoplasms. / Kim, Eunkyung; Jang, Mi; Park, Minhee; Kim, Hoguen.

In: Oncotarget, Vol. 8, No. 55, 01.11.2017, p. 93404-93413.

Research output: Contribution to journalArticle

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