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Nuclear Expression of E-Cadherin in Solid Pseudopapillary Tumors of the Pancreas

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Nuclear Expression of E-Cadherin in Solid Pseudopapillary Tumors of the Pancreas JOP. J Pancreas (Online) 2007; 8(3):296-303. ORIGINAL ARTICLE Nuclear Expression of E-Cadherin in Solid Pseudopapillary Tumors of the Pancreas Stefano Serra1, Sima Salahshor2, Mosa Fagih1, Firouzeh Niakosari1, Jasim M Radhi3, Runjan Chetty1 1Department of Pathology, University Health Network/Toronto Medical Laboratories. Toronto, Canada. 2Samuel Lunenfeld Research Institute, Centre for Systems Biology, University of Toronto. Toronto, Canada. 3Department of Pathology and Molecular Medicine, McMaster University. Hamilton, Canada ABSTRACT trypsin diffusely positive (50% or more of the tumor cells staining) and CD56 showed focal Context Solid pseudopapillary tumors of the positivity in all cases with 5-10% of tumor pancreas are rare and have recently been cells displaying immunolabeling. All cases shown to harbor mutations of the beta-catenin were negative for chromogranin and gene with resultant nuclear localization of synaptophysin. All 18 cases displayed beta-catenin protein to the nucleus. Moreover, cytoplasmic and nuclear localization of beta- there is a close relationship between beta- catenin protein. Similarly, E-cadherin protein catenin and E-cadherin. was localized to the nucleus in all 18 cases, Objective To explore the protein expression with loss of the characteristic membranous of E-cadherin in a series of solid pseudo- decoration of cells. papillary tumors of the pancreas. Conclusion This study is the first Participants Eighteen cases of solid demonstration of aberrant nuclear localization pseudopapillary tumors of the pancreas. of E-cadherin protein in solid pseudopapillary tumors of the pancreas. Whilst the exact Design The cases were studied using a tissue mechanism is not know and nuclear E- microarray that was constructed as follows: cadherin is not related to tumor aggression, for each case, 4 to 14 cores measuring 1.0 mm this staining pattern may be of diagnostic each were drilled from the blocks. Tissue value in concert with beta-catenin staining. cores from normal pancreas were used as controls and for orientation purposes. Main outcome measures The slides were INTRODUCTION stained with the following commercially Decrease in or loss of E-cadherin is available antibodies: CD10, CD56, vimentin, considered a molecular event signaling alpha-1-antitrypsin, alpha-1-antichymo- dysfunction of the cell-cell adhesion system, trypsin, neuron-specific enolase, chromo- thereby triggering invasion and metastasis in granin, synaptophysin, beta-catenin and E- many malignancies. In addition, alterations in cadherin. the cadherin-catenin system may also be Results All the tumors were CD10, vimentin, involved in tumorigenesis. E-cadherin and alpha-1-antitrypsin and alpha-1-antichymo- beta-catenin, components of the Wnt signal JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 8, No. 3 - May 2007. [ISSN 1590-8577] 296 JOP. J Pancreas (Online) 2007; 8(3):296-303. transduction pathway, may serve as a correlate immunoexpression with clinico- common switch in central processes that pathological parameters. regulate cellular differentiation and growth. Abnormalities of expression of beta-catenin MATERIALS AND METHODS protein and in the gene have been reported in solid pseudopapillary tumors (SPT) of the Eighteen cases of SPT of the pancreas were pancreas, and are considered a recurring, utilized for tissue microarray analysis (TMA): consistent finding associated with these 10 were retrieved from the archives of the lesions [1, 2]. SPT are rare neoplasms with a Department of Pathology, University Heath low malignant potential occurring most Network, Toronto, and 8 from the Department frequently in young women. Histologically, it of Pathology, McMaster University, is a solid and cystic tumor with a prominent Hamilton. vascular network and degenerative pseudo- papillae [3]. Often times they may resemble Tissue Microarray Analysis Construction endocrine tumors of the pancreas very closely because of the vascular network and relatively For each case, 4 to 14 cores measuring 1.0 uniform cytological appearance. These tumors mm each were drilled from the blocks. Tissue are composed of small uniform cells with cores from normal pancreas were used as nuclei that can show grooves and irregular controls and for orientation purposes. contours. Size of tumor, necrosis, gross invasive- The neoplastic cells in SPT are consistently ness/demarcation, lymphovascular invasion, vimentin, CD10 and CD56-positive and lymph node involvement and liver metastasis nuclear beta-catenin expression is also a well- were recorded. The mitotic count, expressed recognized feature. Some cases express focal per 10 high powered fields (HPFs) was positivity for alpha-1-antitrypsin, alpha-1- assessed. antichymotrypsin, neuron-specific enolase and synaptophysin. Immunohistochemistry In view of the association between E-cadherin and beta-catenin, the purpose of this study All the TMA blocks were stained with a panel was to examine expression of E-cadherin in a of antibodies used in the routine work-up of series of SPT using a tissue microarray and to SPTs, in addition to including beta-catenin Table 1. Antibodies used. Antibody Source Dilution Retrieval method Clone CD10 Ventana, Tucson, AZ, USA Prediluted Heat a 56C6 Vimentin American Research Products, 1/1,200 Protease VIM3B4 Belmont, MA, USA alpha-1-antitrypsin Ventana, Tucson, AZ, USA Prediluted Heat a Polyclonal alpha-1-antichymotrypsin Dakocytomation, Glostrup, Denmark Prediluted Heat a Polyclonal CD56 Zymed, Carlsbad, CA, USA 1/100 Heat a 123C3 Neuron-specific enolase Dakocytomation, Glostrup, Denmark 1/100 No retrieval Polyclonal Chromogranin Ventana, Tucson,AZ, USA Prediluted No retrieval Monoclonal Synaptophysin Dakocytomation, Glostrup, Denmark 1/100 No retrieval Monoclonal beta-catenin BD-Transduction Laboratories, 1/3,000 Heat (Microwave) 14 Franklin Lake, NJ, USA E-cadherin BD-Transduction Laboratories, 1/2,000 Heat (Microwave) 36 Franklin Lake, NJ, USA a BenchMark®, Ventana Medical System, Inc., Tucson, AZ, USA. JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 8, No. 3 - May 2007. [ISSN 1590-8577] 297 JOP. J Pancreas (Online) 2007; 8(3):296-303. and E-cadherin which form the main thrust of ETHICS this study (Table 1). Tissue sections were cut using sterile disposable microtome blades on Written informed consent was obtained from a rotary microtome. They were floated on a each patient and the study protocol conforms water bath (50°C) and picked up on poly-L- to the ethical guidelines of the "World lysine coated glass slides. The sections were Medical Association Declaration of Helsinki - baked on a hot plate at 60°C for 20 minutes. Ethical Principles for Medical Research Deparaffinization was carried out in 2 Involving Human Subjects" adopted by the changes of xylene for 5 minutes each. This 18th WMA General Assembly, Helsinki, was followed by rehydration in 2 changes of Finland, June 1964, as revised in Tokyo 2004, absolute ethanol for 3 minutes each and 2 as reflected in a priori approval by the changes of 95% ethanol for 3 minutes each appropriate institutional review committee. before a stay of 5 minutes under running tap water. For the antibodies requiring microwave STATISTICS heat retrieval, the sections were processed to unmask antigens by conventional microwave Means, ranges, and frequencies were heating in 0.01 M sodium citrate retrieval evaluated as descriptive statistics. The Mann- buffer (Table 1). The other heat retrieval Whitney U-test was applied to compare cases method is indicated in Table 1. with and without metastases. Two-tailed P Appropriate positive controls (cases known to values less than 0.05 were considered be positive for all antibodies used in the significant. Data were analyzed by using the study) were run in parallel. SPTs were SPSS for Windows (version 13.0) package. regarded as positive for a particular antibody if the tumor cells displayed a similar staining RESULTS pattern and intensity as the known positive control. Specifically, membranous immuno- Patient and tumor characteristics of the 18 reactivity for E-cadherin/beta-catenin was cases of solid pseudopapillary tumor of the considered normal; any reduction or loss of pancreas are shown in Table 2. Sixteen of the this pattern of immunoreactivity compared to 18 cases were in female patients, 2 were normal tissue, together with nuclear and/or males, ranging in age from 11 to 62 years cytoplasmic staining was considered as (average: 38.0 years). Fifteen tumors arose in abnormal immunoexpression. the tail/body of the pancreas, while 3 (16.7%) Table 2. Patient and tumor characteristics of the 18 cases of solid pseudopapillary tumor of the pancreas. ID Sex Age (years) Size (cm) Location Metastases 1 F 32 5.2 Head Liver a 2 F 40 6.8 Tail No 3 F 45 5.5 Body, tail No 4 F 39 3.5 Head, body No 5 F 24 4.5 Head No 6 F 31 8.8 Tail No 7 F 43 4.0 Tail No 8 M 45 3.5 Tail No 9 F 39 3.2 Tail No 10 F 20 3.1 Body Liver 11 F 43 13.0 Tail Liver 12 F 39 6.3 Tail No 13 F 11 8.0 Body, tail No 14 F 61 9.0 Tail Liver 15 M 62 17.0 Body, tail No 16 F 40 4.5 Tail No 17 F 52 2.0 Body No 18 F 19 5.3 Body No a This patients had a liver recurrence one year later after the resection of the primary tumor. JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 8, No. 3 - May 2007. [ISSN 1590-8577] 298 JOP. J Pancreas (Online) 2007; 8(3):296-303. Figure 1. High power illustration of the cytology of a Figure 3. Intense nuclear labeling for beta-catenin solid pseudopapillary tumor with clear cells, many of (anti-beta-catenin x400). which contain indented and irregularly shaped nuclei (H&E x400). inconspicuous. Periodic acid Schiff (PAS) and PAS following diastase digestion (PASD) were located in the head. The size of SPT positive hyaline globules were variably found ranged from 2 to 17 cm, with a mean size of in the cytoplasm and/or in the intercellular 6.3 cm.
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