Abstract
This chapter provides a practical overview of frequently used markers in the diagnosis and differential diagnosis of both common and rare pancreatic and ampullary neoplasms, with a specific focus on pancreatic ductal adenocarcinoma and its mimickers, neuroendocrine neoplasms, acinic cell carcinoma and solid and pseudopapillary neoplasm of the pancreas. The chapter contains 40 questions; each question is addressed with a table, concise note and representative pictures if applicable. In addition to the literature review, the authors have included their own experience and tested numerous antibodies reported in the literature. The most effective diagnostic panels of antibodies have been recommended for many entities, such as pVHL, maspin, S100P and IMP-3 being suggested as the best diagnostic panel for identifying pancreatic ductal adenocarcinoma. Some newly described markers such as PAX8, islet-1 and PDX-1 for neuroendocrine neoplasm have been discussed. Furthermore, immunophenotypes of normal pancreatic and ampullary tissues have been described, which tends to be neglected in the literature.
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Keywords
- Ductal adenocarcinoma
- Pancreatic neuroendocrine neoplasm
- Acinar cell carcinoma
- Solid-pseudopapillary neoplasm
- Intraductal papillary mucinous neoplasm
- Mucinous cyst neoplasm
- Serous cystadenoma
- CK7
- CK20
- CK17
- CK19
- pVHL
- Maspin
- S100P
- IMP3
- MUC5AC
- CEA
- DPC4/SMAD4
- p53
- Chromogranin
- Synaptophysin
- Beta-catenin
- PR
- PAX8
- MIC1
- MUC2
Frequently Asked Questions
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25.1.
Summary of applications and limitations of useful markers (Table 25.1)
Table 25.1 Summary of applications and limitations of useful markers -
25.2.
Summary of useful markers for common tumors (Table 25.2)
Table 25.2 Summary of useful markers for common tumors -
25.3.
Markers for normal pancreatic ducts and acini (Table 25.3)
Table 25.3 Markers for normal pancreatic ducts and acini -
25.4.
Markers for ductal adenocarcinoma of the pancreas (Table 25.4)
Table 25.4 Markers for ductal adenocarcinoma of the pancreas Fig. 25.1 
Invasive ductal adenocarcinoma shows loss of expression of pVHL, and normal ducts show membranous and cytoplasmic staining
Fig. 25.2 
High-grade adenocarcinoma shows nuclear and cytoplasmic staining for maspin
Fig. 25.3 
Nuclear and cytoplasmic positivity of S100P in ductal adenocarcinoma, whereas the normal ducts are negative. Note that only nuclear staining or nuclear and cytoplasmic staining is regarded as positive
Fig. 25.4 
Strong cytoplasmic staining for IMP-3 seen in ductal adenocarcinoma
Fig. 25.5 
Double-staining technique (a) showing carcinoma positive for maspin (brown) and normal ducts positive for pVHL (purple). Double-staining technique (b) showing carcinoma positive for S100P (brown) and normal ducts positive for pVHL (purple)
Fig. 25.6 
Ductal adenocarcinoma shows strongly positive cytoplasmic staining for MUC1
Fig. 25.7 
Ductal adenocarcinoma shows strongly positive cytoplasmic staining for MUC5AC
Fig. 25.8 
CA19-9 is not a very useful marker since it is also expressed in normal ducts and acini
Fig. 25.9 
Ductal adenocarcinoma showing membranous staining for mesothelin
Fig. 25.10 
Strong nuclear staining for p53 in ductal adenocarcinoma
Fig. 25.11 
Ductal adenocarcinoma showing loss of expression of DPC4/SMAD4. Note that inflammatory cells and stromal cells show nuclear positivity as an internal positive control
Fig. 25.12 
Ductal adenocarcinoma showing positive staining for DPC4
-
25.5.
Markers for adenosquamous carcinoma of the pancreas (Table 25.5)
Table 25.5 Markers for adenosquamous carcinoma of the pancreas -
25.6.
Markers for colloid carcinoma of the pancreas (Table 25.6)
Table 25.6 Markers for colloid carcinoma of the pancreas Fig. 25.13 
MUC2 is frequently positive in colloid carcinoma and negative in ductal adenocarcinoma
-
25.7.
Markers for medullary carcinoma of the pancreas (Table 25.7)
Table 25.7 Markers for medullary carcinoma of the pancreas Fig. 25.14 
Medullary carcinoma on H&E stained slide. Note that the lymphoid cells serve as an internal positive control
Fig. 25.15 
Loss of expression of microsatellite instability marker MSH6
-
25.8.
Markers for undifferentiated carcinoma of the pancreas (Table 25.8)
Table 25.8 Markers for undifferentiated carcinoma of the pancreas -
25.9.
Markers for hepatoid carcinoma of the pancreas (Table 25.9)
Table 25.9 Markers for hepatoid carcinoma of the pancreas -
25.10.
Markers for signet ring cell carcinoma of the pancreas (Table 25.10)
Table 25.10 Markers for signet ring cell carcinoma of the pancreas -
25.11.
Markers for undifferentiated carcinoma with osteoclast-like giant cells (Table 25.11)
Table 25.11 Markers for undifferentiated carcinoma with osteoclast-like giant cells -
25.12.
Markers for acinar cell carcinoma (Table 25.12)
Table 25.12 Markers for acinar cell carcinoma -
25.13.
Markers for pancreatic neuroendocrine neoplasm (Table 25.13)
Table 25.13 Markers for pancreatic neuroendocrine neoplasm Fig. 25.16 
Lipid-rich variant of pancreatic neuroendocrine neoplasm
Fig. 25.17 
Lipid-rich variant of pancreatic neuroendocrine neoplasm positive for chromogranin
Fig. 25.18 
Show examples of pancreatic neuroendocrine neoplasm
Fig. 25.19 
Pancreatic neuroendocrine neoplasm with positive staining for PR
Fig. 25.20 
Pancreatic neuroendocrine neoplasm with positive staining for PAX8
Fig. 25.21 
Pancreatic neuroendocrine neoplasm with positive staining for islet-1
-
25.14.
Markers for solid and pseudopapillary neoplasm of the pancreas (Table 25.14)
Table 25.14 Markers for solid-pseudopapillary neoplasm of the pancreas Fig. 25.22 
Solid-pseudopapillary tumor
Fig. 25.23 
Solid-pseudopapillary tumor showing nuclear and cytoplasmic staining for beta-catenin. Note that normal pancreatic duct shows membranous staining for beat-cadherin
Fig. 25.24 
Solid-pseudopapillary tumor showing loss of E-cadherin. Note that normal pancreatic ducts positive for E-cadherin
Fig. 25.25 
Solid-pseudopapillary tumor positive for CD10
-
25.15.
Markers for pancreatoblastoma (Table 25.15)
Table 25.15 Markers for pancreatoblastoma -
25.16.
Markers for serous cystadenoma (Table 25.16)
Table 25.16 Markers for serous cystadenoma Fig. 25.26 
Solid variant of serous microcystic adenoma
Fig. 25.27 
Solid variant of serous microcystic adenoma positive for pVHL
Fig. 25.28 
Solid variant of serous microcystic adenoma positive for MUC6
Fig. 25.29 
Solid variant of serous microcystic adenoma positive for inhibin-alpha
-
25.17.
Markers for mucinous cystic neoplasm (Table 25.17)
Table 25.17 Markers for mucinous cystic neoplasm -
25.18.
Markers for intraductal papillary mucinous neoplasm (Table 25.18)
Table 25.18 Markers for intraductal papillary mucinous neoplasm -
25.19.
Markers for intraductal oncocytic papillary neoplasm (Table 25.19)
Table 25.19 Markers for intraductal oncocytic papillary neoplasm -
25.20.
Markers for pancreatic intraepithelial neoplasia 1 and 2 (Table 25.20)
Table 25.20 Markers for pancreatic intraepithelial neoplasia 1 and 2 -
25.21.
Markers for pancreatic intraepithelial neoplasia 3 (Table 25.21)
Table 25.21 Markers for pancreatic intraepithelial neoplasia 3 -
25.22.
Markers for intraductal tubular neoplasm of the pancreas (Table 25.22)
Table 25.22 Markers for intraductal tubular neoplasm of the pancreas -
25.23.
Markers for chronic pancreatitis (Table 25.23)
Table 25.23 Markers for chronic pancreatitis Fig. 25.30 
Show an example of autoimmune pancreatitis
Fig. 25.31 
Show an example of autoimmune pancreatitis with many IgG4-positive plasma cells
Differential Diagnosis
-
25.24.
Ductal adenocarcinoma vs. chronic pancreatitis (Table 25.24)
Table 25.24 Ductal adenocarcinoma vs. chronic pancreatitis -
25.25.
Pancreatic neuroendocrine neoplasm vs. solid pseudopapillary neoplasm (Table 25.25)
Table 25.25 Pancreatic neuroendocrine tumor vs. solid pseudopapillary neoplasm -
25.26.
Pancreatic neuroendocrine neoplasm vs. acinar cell carcinoma (Table 25.26)
Table 25.26 Pancreatic neuroendocrine neoplasm vs. acinar cell carcinoma -
25.27.
Pancreatic neuroendocrine neoplasm vs. pancreatoblastoma (Table 25.27)
Table 25.27 Pancreatic neuroendocrine tumor vs. pancreatoblastoma -
25.28.
Acinar cell carcinoma vs. solid pseudopapillary neoplasm (Table 25.28)
Table 25.28 Acinar cell carcinoma vs. solid pseudopapillary neoplasm -
25.29.
Acinar cell carcinoma vs. ductal adenocarcinoma (Table 25.29)
Table 25.29 Acinar cell carcinoma vs. ductal adenocarcinoma -
25.30.
Acinar cell carcinoma vs. pancreatoblastoma (Table 25.30)
Table 25.30 Acinar cell carcinoma vs. pancreatoblastoma -
25.31.
Solid pseudopapillary neoplasm vs. pancreatoblastoma (Table 25.31)
Table 25.31 Solid pseudopapillary neoplasm vs. pancreatoblastoma -
25.32.
Markers for hematopoietic malignancies in the pancreas (Table 25.32)
Table 25.32 Markers for hematopoietic malignancies in the pancreas -
25.33.
Metastases in the pancreas (Table 25.33)
Table 25.33 Metastases in the pancreas -
25.34.
Prognostic markers for pancreatic adenocarcinoma (Table 25.34)
Table 25.34 Prognostic markers in pancreatic adenocarcinoma -
25.35.
Predictive markers for pancreatic neuroendocrine neoplasm (Table 25.35)
Table 25.35 Predictive markers for pancreatic neuroendocrine neoplasm
Ampulla
-
25.36.
Markers for normal ampulla of Vater (Table 25.36)
Table 25.36 Markers for normal ampulla of Vater -
25.37.
Markers for ampullary adenocarcinoma—intestinal type (Table 25.37)
Table 25.37 Markers for ampullary adenocarcinoma—intestinal type -
25.38.
Markers for ampullary adenocarcinoma—pancreatobiliary type (Table 25.38)
Table 25.38 Markers for ampullary adenocarcinoma—pancreatobiliary type -
25.39.
Ampullary adenocarcinoma—intestinal type vs. pancreatobiliary type (Table 25.39)
Table 25.39 Ampullary adenocarcinoma, intestinal type vs. pancreatobiliary type -
25.40.
Ampullary adenocarcinoma vs. pancreatic adenocarcinoma (Table 25.40)
Table 25.40 Ampullary adenocarcinoma vs. pancreatic adenocarcinoma
Note for All Tables
Note: “+”, usually greater than 70 % of cases are positive; “−”, less than 5 % of cases are positive; “+ or −”, usually more than 50 % of cases are positive; “− or +”, less than 50 % of cases are positive. ND no data available, V variable.
References
Hruban RH, Pitman MB, Klimstra DS. AFIP Atlas of tumor pathology; tumors of the pancreas. Vol fourth series. Fascicle 6 ed. Washington, DC: American Registry of Pathology; 2007.
Chu PG, Weiss LM. Modern immunohistochemistry. New York: Cambridge University Press; 2009.
Dabbs DJ. Diagnostic immunohistochemistry. 3rd ed. Philadelphia, PA: Churchill Livingstone Elsevier; 2014.
Hruban RH, Boffetta P, Hiraoka N, et al. Ductal adenocarcinoma of the pancreas. In: Bosman FT, Carneiro F, Hruban RH, Theise ND, editors. WHO classification of tumours of the digestive system. 4th ed. Lyon: IARC Press; 2010. p. 279–334.
Goldstein NS, Bassi D. Cytokeratins 7, 17, and 20 reactivity in pancreatic and ampulla of Vater adenocarcinomas. Percentage of positivity and distribution is affected by the cut-point threshold. Am J Clin Pathol. 2001;115(5):695–702.
Hornick JL, Lauwers GY, Odze RD. Immunohistochemistry can help distinguish metastatic pancreatic adenocarcinomas from bile duct adenomas and hamartomas of the liver. Am J Surg Pathol. 2005;29(3):381–9.
Chu P, Wu E, Weiss LM. Cytokeratin 7 and cytokeratin 20 expression in epithelial neoplasms: a survey of 435 cases. Mod Pathol. 2000;13(9):962–72.
Chu PG, Schwarz RE, Lau SK, Yen Y, Weiss LM. Immunohistochemical staining in the diagnosis of pancreatobiliary and ampulla of Vater adenocarcinoma: application of CDX2, CK17, MUC1, and MUC2. Am J Surg Pathol. 2005;29(3):359–67.
Lau SK, Prakash S, Geller SA, Alsabeh R. Comparative immunohistochemical profile of hepatocellular carcinoma, cholangiocarcinoma, and metastatic adenocarcinoma. Hum Pathol. 2002;33(12):1175–81.
Bhardwaj A, Marsh Jr WL, Nash JW, Barbacioru CC, Jones S, Frankel WL. Double immunohistochemical staining with MUC4/p53 is useful in the distinction of pancreatic adenocarcinoma from chronic pancreatitis: a tissue microarray-based study. Arch Pathol Lab Med. 2007;131(4):556–62.
Coppola D, Lu L, Fruehauf JP, et al. Analysis of p53, p21WAF1, and TGF-beta1 in human ductal adenocarcinoma of the pancreas: TGF-beta1 protein expression predicts longer survival. Am J Clin Pathol. 1998;110(1):16–23.
Apple SK, Hecht JR, Lewin DN, Jahromi SA, Grody WW, Nieberg RK. Immunohistochemical evaluation of K-ras, p53, and HER-2/neu expression in hyperplastic, dysplastic, and carcinomatous lesions of the pancreas: evidence for multistep carcinogenesis. Hum Pathol. 1999;30(2):123–9.
DiGiuseppe JA, Hruban RH, Goodman SN, et al. Overexpression of p53 protein in adenocarcinoma of the pancreas. Am J Clin Pathol. 1994;101(6):684–8.
Werling RW, Yaziji H, Bacchi CE, Gown AM. CDX2, a highly sensitive and specific marker of adenocarcinomas of intestinal origin: an immunohistochemical survey of 476 primary and metastatic carcinomas. Am J Surg Pathol. 2003;27(3):303–10.
Moskaluk CA, Zhang H, Powell SM, Cerilli LA, Hampton GM, Frierson Jr HF. Cdx2 protein expression in normal and malignant human tissues: an immunohistochemical survey using tissue microarrays. Mod Pathol. 2003;16(9):913–9.
De Lott LB, Morrison C, Suster S, Cohn DE, Frankel WL. CDX2 is a useful marker of intestinal-type differentiation: a tissue microarray-based study of 629 tumors from various sites. Arch Pathol Lab Med. 2005;129(9):1100–5.
Yantiss RK, Woda BA, Fanger GR, et al. KOC (K homology domain containing protein overexpressed in cancer): a novel molecular marker that distinguishes between benign and malignant lesions of the pancreas. Am J Surg Pathol. 2005;29(2):188–95.
Zhao H, Mandich D, Cartun RW, Ligato S. Expression of K homology domain containing protein overexpressed in cancer in pancreatic FNA for diagnosing adenocarcinoma of pancreas. Diagn Cytopathol. 2007;35(11):700–4.
Kashima K, Ohike N, Mukai S, Sato M, Takahashi M, Morohoshi T. Expression of the tumor suppressor gene maspin and its significance in intraductal papillary mucinous neoplasms of the pancreas. Hepatobiliary Pancreat Dis Int. 2008;7(1):86–90.
Agarwal B, Ludwig OJ, Collins BT, Cortese C. Immunostaining as an adjunct to cytology for diagnosis of pancreatic adenocarcinoma. Clin Gastroenterol Hepatol. 2008;6(12):1425–31.
Ohike N, Maass N, Mundhenke C, et al. Clinicopathological significance and molecular regulation of maspin expression in ductal adenocarcinoma of the pancreas. Cancer Lett. 2003;199(2):193–200.
Cao D, Zhang Q, Wu LS, et al. Prognostic significance of maspin in pancreatic ductal adenocarcinoma: tissue microarray analysis of 223 surgically resected cases. Mod Pathol. 2007;20(5):570–8.
Wente MN, Jain A, Kono E, et al. Prostate stem cell antigen is a putative target for immunotherapy in pancreatic cancer. Pancreas. 2005;31(2):119–25.
Argani P, Rosty C, Reiter RE, et al. Discovery of new markers of cancer through serial analysis of gene expression: prostate stem cell antigen is overexpressed in pancreatic adenocarcinoma. Cancer Res. 2001;61(11):4320–4.
McCarthy DM, Maitra A, Argani P, et al. Novel markers of pancreatic adenocarcinoma in fine-needle aspiration: mesothelin and prostate stem cell antigen labeling increases accuracy in cytologically borderline cases. Appl Immunohistochem Mol Morphol. 2003;11(3):238–43.
Ordonez NG. Application of mesothelin immunostaining in tumor diagnosis. Am J Surg Pathol. 2003;27(11):1418–28.
Hassan R, Laszik ZG, Lerner M, Raffeld M, Postier R, Brackett D. Mesothelin is overexpressed in pancreaticobiliary adenocarcinomas but not in normal pancreas and chronic pancreatitis. Am J Clin Pathol. 2005;124(6):838–45.
Frierson Jr HF, Moskaluk CA, Powell SM, et al. Large-scale molecular and tissue microarray analysis of mesothelin expression in common human carcinomas. Hum Pathol. 2003;34(6):605–9.
Swierczynski SL, Maitra A, Abraham SC, et al. Analysis of novel tumor markers in pancreatic and biliary carcinomas using tissue microarrays. Hum Pathol. 2004;35(3):357–66.
Baruch AC, Wang H, Staerkel GA, Evans DB, Hwang RF, Krishnamurthy S. Immunocytochemical study of the expression of mesothelin in fine-needle aspiration biopsy specimens of pancreatic adenocarcinoma. Diagn Cytopathol. 2007;35(3):143–7.
Jhala N, Jhala D, Vickers SM, et al. Biomarkers in diagnosis of pancreatic carcinoma in fine-needle aspirates. Am J Clin Pathol. 2006;126(4):572–9.
Cao D, Maitra A, Saavedra JA, Klimstra DS, Adsay NV, Hruban RH. Expression of novel markers of pancreatic ductal adenocarcinoma in pancreatic nonductal neoplasms: additional evidence of different genetic pathways. Mod Pathol. 2005;18(6):752–61.
Lin F, Shi J, Liu H, et al. Diagnostic utility of S100P and von Hippel-Lindau gene product (pVHL) in pancreatic adenocarcinoma-with implication of their roles in early tumorigenesis. Am J Surg Pathol. 2008;32(1):78–91.
Karanjawala ZE, Illei PB, Ashfaq R, et al. New markers of pancreatic cancer identified through differential gene expression analyses: claudin 18 and annexin A8. Am J Surg Pathol. 2008;32(2):188–96.
Sato N, Fukushima N, Maitra A, et al. Gene expression profiling identifies genes associated with invasive intraductal papillary mucinous neoplasms of the pancreas. Am J Pathol. 2004;164(3):903–14.
Tsukahara M, Nagai H, Kamiakito T, et al. Distinct expression patterns of claudin-1 and claudin-4 in intraductal papillary-mucinous tumors of the pancreas. Pathol Int. 2005;55(2):63–9.
Hewitt KJ, Agarwal R, Morin PJ. The claudin gene family: expression in normal and neoplastic tissues. BMC Cancer. 2006;6:186.
Chhieng DC, Benson E, Eltoum I, et al. MUC1 and MUC2 expression in pancreatic ductal carcinoma obtained by fine-needle aspiration. Cancer. 2003;99(6):365–71.
Giorgadze TA, Peterman H, Baloch ZW, et al. Diagnostic utility of mucin profile in fine-needle aspiration specimens of the pancreas: an immunohistochemical study with surgical pathology correlation. Cancer. 2006;108(3):186–97.
Luttges J, Zamboni G, Longnecker D, Kloppel G. The immunohistochemical mucin expression pattern distinguishes different types of intraductal papillary mucinous neoplasms of the pancreas and determines their relationship to mucinous noncystic carcinoma and ductal adenocarcinoma. Am J Surg Pathol. 2001;25(7):942–8.
Deng H, Shi J, Wilkerson M, Meschter S, Dupree W, Lin F. Usefulness of S100P in diagnosis of adenocarcinoma of pancreas on fine-needle aspiration biopsy specimens. Am J Clin Pathol. 2008;129(1):81–8.
Dowen SE, Crnogorac-Jurcevic T, Gangeswaran R, et al. Expression of S100P and its novel binding partner S100PBPR in early pancreatic cancer. Am J Pathol. 2005;166(1):81–92.
Sato N, Fukushima N, Matsubayashi H, Goggins M. Identification of maspin and S100P as novel hypomethylation targets in pancreatic cancer using global gene expression profiling. Oncogene. 2004;23(8):1531–8.
Yamaguchi H, Inoue T, Eguchi T, et al. Fascin overexpression in intraductal papillary mucinous neoplasms (adenomas, borderline neoplasms, and carcinomas) of the pancreas, correlated with increased histological grade. Mod Pathol. 2007;20(5):552–61.
Notohara K, Hamazaki S, Tsukayama C, et al. Solid-pseudopapillary tumor of the pancreas: immunohistochemical localization of neuroendocrine markers and CD10. Am J Surg Pathol. 2000;24(10):1361–71.
Abraham SC, Klimstra DS, Wilentz RE, et al. Solid-pseudopapillary tumors of the pancreas are genetically distinct from pancreatic ductal adenocarcinomas and almost always harbor beta-catenin mutations. Am J Pathol. 2002;160(4):1361–9.
Tanaka Y, Kato K, Notohara K, et al. Frequent beta-catenin mutation and cytoplasmic/nuclear accumulation in pancreatic solid-pseudopapillary neoplasm. Cancer Res. 2001;61(23):8401–4.
Audard V, Cavard C, Richa H, et al. Impaired E-cadherin expression and glutamine synthetase overexpression in solid pseudopapillary neoplasm of the pancreas. Pancreas. 2008;36(1):80–3.
Chetty R, Serra S. Membrane loss and aberrant nuclear localization of E-cadherin are consistent features of solid pseudopapillary tumour of the pancreas. An immunohistochemical study using two antibodies recognizing different domains of the E-cadherin molecule. Histopathology. 2008;52(3):325–30.
El-Bahrawy MA, Rowan A, Horncastle D, et al. E-cadherin/catenin complex status in solid pseudopapillary tumor of the pancreas. Am J Surg Pathol. 2008;32(1):1–7.
Comper F, Antonello D, Beghelli S, et al. Expression pattern of claudins 5 and 7 distinguishes solid-pseudopapillary from pancreatoblastoma, acinar cell and endocrine tumors of the pancreas. Am J Surg Pathol. 2009;33(5):768–74.
Pettinato G, Manivel JC, Ravetto C, et al. Papillary cystic tumor of the pancreas. A clinicopathologic study of 20 cases with cytologic, immunohistochemical, ultrastructural, and flow cytometric observations, and a review of the literature. Am J Clin Pathol. 1992;98(5):478–88 [see comment: erratum appears in Am J Clin Pathol 1993 Jun;99(6):764].
Klimstra DS, Wenig BM, Adair CF, Heffess CS. Pancreatoblastoma. A clinicopathologic study and review of the literature. Am J Surg Pathol. 1995;19(12):1371–89.
Abraham SC, Wu TT, Klimstra DS, et al. Distinctive molecular genetic alterations in sporadic and familial adenomatous polyposis-associated pancreatoblastomas: frequent alterations in the APC/beta-catenin pathway and chromosome 11p. Am J Pathol. 2001;159(5):1619–27.
Abraham SC, Wu TT, Hruban RH, et al. Genetic and immunohistochemical analysis of pancreatic acinar cell carcinoma: frequent allelic loss on chromosome 11p and alterations in the APC/beta-catenin pathway. Am J Pathol. 2002;160(3):953–62.
Kerr NJ, Chun YH, Yun K, Heathcott RW, Reeve AE, Sullivan MJ. Pancreatoblastoma is associated with chromosome 11p loss of heterozygosity and IGF2 overexpression. Med Pediatr Oncol. 2002;39(1):52–4.
Tanaka Y, Kato K, Notohara K, et al. Significance of aberrant (cytoplasmic/nuclear) expression of beta-catenin in pancreatoblastoma. J Pathol. 2003;199(2):185–90.
van Heek T, Rader AE, Offerhaus GJ, et al. K-ras, p53, and DPC4 (MAD4) alterations in fine-needle aspirates of the pancreas: a molecular panel correlates with and supplements cytologic diagnosis. Am J Clin Pathol. 2002;117(5):755–65.
Lu SH, Yuan RH, Chen YL, Hsu HC, Jeng YM. Annexin A10 is an immunohistochemical marker for adenocarcinoma of the upper gastrointestinal tract and pancreatobiliary system. Histopathology. 2013;63(5):640–8.
Bausch D, Thomas S, Mino-Kenudson M, et al. Plectin-1 as a novel biomarker for pancreatic cancer. Clin Cancer Res. 2011;17(2):302–9.
Chung YT, Matkowskyj KA, Li H, et al. Overexpression and oncogenic function of aldo-keto reductase family 1B10 (AKR1B10) in pancreatic carcinoma. Mod Pathol. 2012;25(5):758–66.
Lin F, Shi J, Zhu, S, et al. Cadherin-17 and SATB2 are sensitive and specific immunomarkers for medullary carcinoma of the large intestine. Arch Pathol Lab Med. 2014;138(8):1015–26.
Hosoda W, Sasaki E, Murakami Y, Yamao K, Shimizu Y, Yatabe Y. BCL10 as a useful marker for pancreatic acinar cell carcinoma, especially using endoscopic ultrasound cytology specimens. Pathol Int. 2013;63(3):176–82.
La Rosa S, Adsay V, Albarello L, et al. Clinicopathologic study of 62 acinar cell carcinomas of the pancreas: insights into the morphology and immunophenotype and search for prognostic markers. Am J Surg Pathol. 2012;36(12):1782–95.
Mounajjed T, Zhang L, Wu TT. Glypican-3 expression in gastrointestinal and pancreatic epithelial neoplasms. Hum Pathol. 2013;44(4):542–50.
Sangoi AR, Ohgami RS, Pai RK, Beck AH, McKenney JK, Pai RK. PAX8 expression reliably distinguishes pancreatic well-differentiated neuroendocrine tumors from ileal and pulmonary well-differentiated neuroendocrine tumors and pancreatic acinar cell carcinoma. Mod Pathol. 2011;24(3):412–24.
Tacha D, Qi W, Zhou D, Bremer R, Cheng L. PAX8 mouse monoclonal antibody [BC12] recognizes a restricted epitope and is highly sensitive in renal cell and ovarian cancers but does not cross-react with B cells and tumors of pancreatic origin. Appl Immunohistochem Mol Morphol. 2013;21(1):59–63.
Lin F, Shi J, Wilkerson M, Liu H. SALL4 and PAX8 expression in carcinomas from various organs [USCAP abstract 956]. Mod Pathol. 2013;26(2s):230A.
Lorenzo PI, Jimenez Moreno CM, Delgado I, et al. Immunohistochemical assessment of Pax8 expression during pancreatic islet development and in human neuroendocrine tumors. Histochem Cell Biol. 2011;136(5):595–607.
Graham RP, Shrestha B, Caron BL, et al. Islet-1 is a sensitive but not entirely specific marker for pancreatic neuroendocrine neoplasms and their metastases. Am J Surg Pathol. 2013;37(3):399–405.
Koo J, Mertens RB, Mirocha JM, Wang HL, Dhall D. Value of Islet 1 and PAX8 in identifying metastatic neuroendocrine tumors of pancreatic origin. Mod Pathol. 2012;25(6):893–901.
Agaimy A, Erlenbach-Wünsch K, Konukiewitz B, et al. ISL1 expression is not restricted to pancreatic well-differentiated neuroendocrine neoplasms, but is also commonly found in well and poorly differentiated neuroendocrine neoplasms of extrapancreatic origin. Mod Pathol. 2013;26(7):995–1003.
Hermann G, Konukiewitz B, Schmitt A, Perren A, Klöppel G. Hormonally defined pancreatic and duodenal neuroendocrine tumors differ in their transcription factor signatures: expression of ISL1, PDX1, NGN3, and CDX2. Virchows Arch. 2011;459(2):147–54.
Guo Y, Yuan F, Deng H, Wang HF, Jin XL, Xiao JC. Paranuclear dot-like immunostaining for CD99: a unique staining pattern for diagnosing solid-pseudopapillary neoplasm of the pancreas. Am J Surg Pathol. 2011;35(6):799–806.
Kanehira K, Khoury T. Neuroendocrine markers expression in pancreatic serous cystadenoma. Appl Immunohistochem Mol Morphol. 2011;19(2):141–6.
Liu H, Shi J, Wang HL, et al. Expression of von Hippel-Lindau gene product (pVHL) and S100P in cystic neoplasms of the pancreas–with an implication for their roles in tumorigenesis. Ann Clin Lab Sci. 2012;42(2):109–17.
Kashima K, Ohike N, Mukai S, Sato M, Takahashi M, Morohoshi T. Expression of the tumor suppressor gene maspin and its significance in intraductal papillary mucinous neoplasms of the pancreas. Hepatobiliary Pancreat Dis Int. 2008;7(1):86–90.
Ueda M, Miura Y, Kunihiro O, et al. MUC1 overexpression is the most reliable marker of invasive carcinoma in intraductal papillary-mucinous tumor (IPMT). Hepatogastroenterology. 2005;52(62):398–403.
Dhall D, Suriawinata AA, Tang LH, Shia J, Klimstra DS. Use of immunohistochemistry for IgG4 in the distinction of autoimmune pancreatitis from peritumoral pancreatitis. Hum Pathol. 2010;41(5):643–52.
Detlefsen S, Bräsen JH, Zamboni G, Capelli P, Klöppel G. Deposition of complement C3c, immunoglobulin (Ig) G4 and IgG at the basement membrane of pancreatic ducts and acini in autoimmune pancreatitis. Histopathology. 2010;57(6):825–35.
Deshpande V, Gupta R, Sainani N, et al. Subclassification of autoimmune pancreatitis: a histologic classification with clinical significance. Am J Surg Pathol. 2011;35(1):26–35.
Adsay NV, Pierson C, Sarkar F, et al. Colloid (mucinous noncystic) carcinoma of the pancreas. Am J Surg Pathol. 2001;25(1):26–42.
Wilentz RE, Goggins M, Redston M, et al. Genetic, immunohistochemical, and clinical features of medullary carcinoma of the pancreas: a newly described and characterized entity. Am J Pathol. 2000;156(5):1641–51.
Banville N, Geraghty R, Fox E, et al. Medullary carcinoma of the pancreas in a man with hereditary nonpolyposis colorectal cancer due to a mutation of the MSH2 mismatch repair gene. Hum Pathol. 2006;37(11):1498–502.
Nakata B, Wang YQ, Yashiro M, et al. Negative hMSH2 protein expression in pancreatic carcinoma may predict a better prognosis of patients. Oncol Rep. 2003;10(4):997–1000.
Winter JM, Ting AH, Vilardell F, et al. Absence of E-cadherin expression distinguishes noncohesive from cohesive pancreatic cancer. Clin Cancer Res. 2008;14(2):412–8.
Hameed O, Xu H, Saddeghi S, Maluf H. Hepatoid carcinoma of the pancreas: a case report and literature review of a heterogeneous group of tumors. Am J Surg Pathol. 2007;31(1):146–52.
Kosmahl M, Wagner J, Peters K, Sipos B, Kloppel G. Serous cystic neoplasms of the pancreas: an immunohistochemical analysis revealing alpha-inhibin, neuron-specific enolase, and MUC6 as new markers. Am J Surg Pathol. 2004;28(3):339–46.
Handra-Luca A, Flejou JF, Rufat P, et al. Human pancreatic mucinous cystadenoma is characterized by distinct mucin, cytokeratin and CD10 expression compared with intraductal papillary-mucinous adenoma. Histopathology. 2006;48(7):813–21.
Ueda M, Miura Y, Kunihiro O, et al. MUC1 overexpression is the most reliable marker of invasive carcinoma in intraductal papillary-mucinous tumor (IPMT). Hepatogastroenterology. 2005;52(62):398–403.
Swerdlow H, Campo E, Harris N, et al. WHO classification of tumours of haematopoietic and lymphoid tissues. 4th edn. Lyon: International Agency for Research on Cancer; 2008, p 439. Accessed 10/1/2009.
Higgins JP, Kaygusuz G, Wang L, et al. Placental S100 (S100P) and GATA3: markers for transitional epithelium and urothelial carcinoma discovered by complementary DNA microarray. Am J Surg Pathol. 2007;31(5):673–80.
Liu H, Shi J, Wilkerson ML, Lin F. Immunohistochemical evaluation of GATA3 expression in tumors and normal tissues: a useful immunomarker for breast and urothelial carcinomas. Am J Clin Pathol. 2012;138(1):57–64.
So JS, Epstein JI. GATA3 expression in paragangliomas: a pitfall potentially leading to misdiagnosis of urothelial carcinoma. Mod Pathol. 2013;26(10):1365–70.
Schwartz LE, Begum S, Westra WH, Bishop JA. GATA3 immunohistochemical expression in salivary gland. Head Neck Pathol. 2013;7(4):311–5.
Chu P, Arber DA. Paraffin-section detection of CD10 in 505 nonhematopoietic neoplasms. Frequent expression in renal cell carcinoma and endometrial stromal sarcoma. Am J Clin Pathol. 2000;113(3):374–82.
Wang W, Gao J, Man XH, Li ZS, Gong YF. Significance of DNA methyltransferase-1 and histone deacetylase-1 in pancreatic cancer. Oncol Rep. 2009;21(6):1439–47.
Hildenbrand R, Niedergethmann M, Marx A, et al. Amplification of the urokinase-type plasminogen activator receptor (uPAR) gene in ductal pancreatic carcinomas identifies a clinically high-risk group. Am J Pathol. 2009;174(6):2246–53.
Fong D, Hermann M, Untergasser G, et al. Dkk-3 expression in the tumor endothelium: a novel prognostic marker of pancreatic adenocarcinomas. Cancer Sci. 2009;100(8):1414–20.
Kahlert C, Weber H, Mogler C, et al. Increased expression of ALCAM/CD166 in pancreatic cancer is an independent prognostic marker for poor survival and early tumour relapse. Br J Cancer. 2009;101(3):457–64.
Ali A, Serra S, Asa SL, Chetty R. The predictive value of CK19 and CD99 in pancreatic endocrine tumors. Am J Surg Pathol. 2006;30(12):1588–94.
Pelosi G, Pasini F, Bresaola E, et al. High-affinity monomeric 67-kD laminin receptors and prognosis in pancreatic endocrine tumours. J Pathol. 1997;183(1):62–9.
Imam H, Eriksson B, Oberg K. Expression of CD44 variant isoforms and association to the benign form of endocrine pancreatic tumours. Ann Oncol. 2000;11(3):295–300.
Ohike N, Morohoshi T. Pathological assessment of pancreatic endocrine tumors for metastatic potential and clinical prognosis. Endocr Pathol. 2005;16(1):33–40.
Diaz-Rubio JL, Duarte-Rojo A, Saqui-Salces M, Gamboa-Dominguez A, Robles-Diaz G. Cellular proliferative fraction measured with topoisomerase II alpha predicts malignancy in endocrine pancreatic tumors. Arch Pathol Lab Med. 2004;128(4):426–9.
Goto A, Niki T, Terado Y, Fukushima J, Fukayama M. Prevalence of CD99 protein expression in pancreatic endocrine tumours (PETs). Histopathology. 2004;45(4):384–92.
Grabowski P, Griss S, Arnold CN, et al. Nuclear survivin is a powerful novel prognostic marker in gastroenteropancreatic neuroendocrine tumor disease. Neuroendocrinology. 2005;81(1):1–9.
Zhou H, Schaefer N, Wolff M, Fischer HP. Carcinoma of the ampulla of Vater: comparative histologic/immunohistochemical classification and follow-up. Am J Surg Pathol. 2004;28(7):875–82.
Schirmacher P, Buchler MW. Ampullary adenocarcinoma—differentiation matters. BMC Cancer. 2008;8:251.
Lin F, Zhang PL, Yang XJ, et al. Human kidney injury molecule-1 (hKIM-1): a useful immunohistochemical marker for diagnosing renal cell carcinoma and ovarian clear cell carcinoma. Am J Surg Pathol. 2007;31(3):371–81.
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Lin, F., Wang, H.L. (2015). Pancreas and Ampulla. In: Lin, F., Prichard, J. (eds) Handbook of Practical Immunohistochemistry. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1578-1_25
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