Original contributionLoss of E-cadherin and cytoplasmic-nuclear expression of β-catenin are the most useful immunoprofiles in the diagnosis of solid-pseudopapillary neoplasm of the pancreas
Introduction
Solid-pseudopapillary neoplasm (SPN) of the pancreas is a clinically benign or low-grade malignant tumor that occurs predominantly in young women [1]. SPN is relatively uncommon and accounts for approximately 1% to 2% of all exocrine pancreatic tumors [2]. A typical case of SPN shows relatively uniform tumor cells in a pseudopapillary pattern, variable sclerosis, and cystic degeneration. However, histologic differentiation of SPN from more aggressive pancreatic neoplasms such as pancreatic endocrine neoplasms (PENs) or adenocarcinomas can be difficult because these tumors share common morphological features and immunohistochemical phenotypes [3], [4], [5]. Cystic changes are more common in SPNs but can also be seen in PENs or adenocarcinomas [3]. By contrast, SPNs with predominantly solid growth patterns can mimic PENs owing to the rich vasculature and monomorphic appearance of the tumor cells. Furthermore, SPNs can show neuroendocrine differentiation at both the immunohistochemical and ultrastructural levels, and it is not uncommon for SPNs to be confused with PENs. SPNs can resemble pancreatic adenocarcinomas both clinically and histologically by exhibiting aggressive clinical behavior and significant nuclear atypia [4], [6]. Therefore, it is necessary to identify more reliable ancillary markers that can be used for the differential diagnosis of various pancreatic neoplasms.
Recently, molecular events involved in the pathogenesis of SPNs have been identified. Notably, alterations of activated protein C (APC)/β-catenin pathway are important in the development of SPNs, and almost all SPNs contain mutations in the β-catenin gene [7], [8]. Earlier studies found that the β-catenin–Tcf pathway was not involved in the pathogenesis of pancreatic adenocarcinoma or PEN [9]; however, little attention had been paid to the diagnostic use of β-catenin in SPN.
In the present study, we examined the expression of E-cadherin as well as β-catenin because these 2 molecules are closely related in the regulation of cell adhesion: cadherin-mediated cellular adhesion can be regulated by increased β-catenin–dependent transcription [10], [11]. Furthermore, the results were compared with the expression levels of known epithelial and neuroendocrine markers as well as CD10, which is known to be a specific marker for SPN, to assess the use of β-catenin and E-cadherin for the diagnosis of SPN [5].
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Case selection and clinicopathologic parameters
A total of 504 surgically resected pancreatic tumors with available tissue blocks and 4 biopsy specimens diagnosed as SPN were selected from the records of the Department of Pathology at the Asan Medical Center, Seoul, Korea. Resected specimens were obtained from patients who underwent surgery from July 1995 to March 2006. Of the 4 patients for whom biopsy specimens were analyzed, 3 underwent subsequent resection and were diagnosed with SPN.
All tissues were fixed in 10% buffered formalin and
Demographics of the patients and clinical findings
In total, 412 informative cases were analyzed. The ages of the patients ranged from 12 to 85 years (mean, 57.9 years), and the patients included 210 females and 202 males. Cases of SPN were markedly more common in female patients (83.3%). SPNs were more often involved the pancreatic tail, whereas adenocarcinomas or PENs occurred more often in the pancreatic head of older patients. Two patients with PEN had multiple tumors scattered throughout the pancreas, which were associated with multiple
Discussion
Histologic differentiation of SPN from PEN or pancreatic adenocarcinoma is important because SPNs have much better prognosis compared with PENs or pancreatic adenocarcinomas, with only 10% to 15% of cases recurring or metastasizing. More than 95% of SPNs are cured by complete surgical resection alone [12]. Therefore, immunohistochemical staining is often performed to support the specific diagnosis of pancreatic neoplasms.
The tumor cells of SPN are known to constantly express α1-antitrypsin, α1
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