Expression Pattern of Claudins 5 and 7 Distinguishes Solid-pseudopapillary From Pancreatoblastoma, Acinar Cell and Endocrine Tumors of the Pancreas

Abstract

Solid-pseudopapillary tumor (SPT) of the pancreas is characterized by a discohesive appearance of the neoplastic cells. This has been linked to the displacement of E-cadherin and beta-catenin from their normal membrane location, which prevents adherens junctions to form. The nuclear localization of beta-catenin is also a feature of SPT that helps in differential diagnosis. This latter includes pancreatic endocrine tumor (PET) as SPT may show neuroendocrine differentiation, and pancreatic acinar cell carcinoma (ACC) and pancreatoblastoma (PB) that may often show nuclear beta-catenin staining. However, the role of additional cell-cell adhesion systems remains to be elucidated in SPT, particularly that of claudins that are essential components of tight junctions showing modulated expression in diverse tumor types. We studied 20 SPT, 20 nonfunctioning PET, 7 ACC, 2 PB, and their matched normal pancreas for the immunohistochemical expression of claudin family members 1, 2, 3, 4, 5, and 7, beta-catenin and E-cadherin. All SPT showed intense membrane claudin 5 and cytoplasmic claudin 2 staining, lack of claudins 3 and 4, and positive cytoplasmic claudins 1 and 7 in few cases. Conversely, PET, ACC, and PB showed strong membrane expression of claudin 7 and lack of claudin 5, whereas claudins 1, 2, 3, and 4 showed variable expression among samples. All SPT showed nuclear beta-catenin and lack of E-cadherin membrane staining, whereas PET, ACC, and PB only showed nuclear beta-catenin in 1, 2, and 2 cases, respectively. SPT shows a peculiar claudin expression profile and the highly specific pattern of claudins 5 and 7 differentiates SPT from PET, ACC, and PB.

Limited usefulness of histopathological features in identification of a clinically aggressive solid-pseudopapillary neoplasm of the pancreas

“…Comper et al observed claudin-5 immunoexpression in all 20 SPN tested using conventional tissue sections [26]. We largely confirmed those observations, but 2/12 of our cases were claudin-5 negative and another 4 showed focal and/or weak staining.…”

“…SPN usually express β-catenin (nuclear stain), CD10, CD56, and PgR [24]. Claudin-5 was identified as a new marker of SPN, particularly useful in differential diagnosis of SPN and other 'solid cellular' neoplasms of the pancreas [26].…”

“…IHC stains useful in diagnosis of SPN (β-catenin, CD10, CD56, progesterone receptor (PgR), synaptophysin, p53, Ki-67, claudin-5) were performed [22,[24][25][26]. Details on IHC protocols are described in Supplementary Table I.…”

Adult pancreatoblastoma: A case report and review of the literature

“…In paediatric PB patients, elevated AFP and CEA levels are the most common abnormal serological markers, and elevated AFP expression has been reported in ≤68% of cases (12,24,25,32), By contrast, these PB tumour markers are typically within the normal range in adult patients (1,3). Serum AFP levels may be used to monitor clinical response to therapy or recurrence in those patients whose tumors produce it (32).…”

Expression Pattern and Prognostic Significance of Claudin 1, 4 and 7 in Pancreatic Cancer

“…In a study of a series of the rare pancreatic SPT (solid pseudopapillary tumour) Comper et al (2009) showed that claudin expression profile of this tumor is interesting when compared with claudin expression of the normal pancreas, PET (pancreatic endocrine tumour), ACC (pancreatic acinar cell carcinoma (ACC) and and PB (pancreatoblastoma ) and that the pattern of claudins 5 and 7 expression is highly specific in differentiating SPT from PET, ACC, and PB (Comper et al, 2009). …”