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Subtypes of Pancreatic Adenocarcinoma

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Translational Pancreatic Cancer Research

Part of the book series: Molecular and Translational Medicine ((MOLEMED))

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Abstract

Pancreatic ductal adenocarcinoma (PDAC) represents the most common neoplasm of the pancreas. PDAC is an infiltrating tumor of epithelial origin forming glandular, duct-like structures. Histological subtypes of PDAC exist, and classification is performed according to the WHO classification system, mainly taking into account histomorphological criteria and marker profiles. Recent studies have shown a great deal of morphological heterogeneity in PDAC, which to some extent correlates with a distinct molecular pathogenesis and a different prognosis. However, a clear-cut correlation between morphologic and molecular subtypes is still missing. In this chapter, we provide an overview of the gross, histomorphological, and immunohistochemical characteristics of PDAC. Furthermore, we discuss its different variants according to emerging concepts of tumor heterogeneity in this entity.

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References

  1. Klimstra DS. Nonductal neoplasms of the pancreas. Mod Pathol. 2007;20(Suppl 1):S94–112.

    PubMed  Google Scholar 

  2. Bosman FT, editor. WHO classification of tumours of the digestive system: Reflects the views of a working group that convened for an editorial and consensus conference at the International Agency for Research on Cancer (IARC), Lyon, December 10–12, 2009; third volume of the 4th edition of the WHO series on histological and genetic typing of human tumours. 4th ed., 1. print run. Lyon: IARC; 2010. (World Health Organization classification of tumours3 (der 4. ed.)).

    Google Scholar 

  3. Stanta G, Jahn SW, Bonin S, Hoefler G. Tumour heterogeneity: principles and practical consequences. Virchows Arch. 2016;469(4):371–84.

    CAS  PubMed  Google Scholar 

  4. Burrell RA, Swanton C. Tumour heterogeneity and the evolution of polyclonal drug resistance. Mol Oncol. 2014;8(6):1095–111.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Verbeke C. Morphological heterogeneity in ductal adenocarcinoma of the pancreas - does it matter? Pancreatology. 2016;16(3):295–301.

    PubMed  Google Scholar 

  6. Ryan DP, Hong TS, Bardeesy N. Pancreatic adenocarcinoma. N Engl J Med. 2014;371(11):1039–49.

    CAS  PubMed  Google Scholar 

  7. Matros E, Bailey G, Clancy T, Zinner M, Ashley S, Whang E, et al. Cytokeratin 20 expression identifies a subtype of pancreatic adenocarcinoma with decreased overall survival. Cancer. 2006;106(3):693–702.

    CAS  PubMed  Google Scholar 

  8. Loy TS, Quesenberry JT, Sharp SC. Distribution of CA 125 in adenocarcinomas. An immunohistochemical study of 481 cases. Am J Clin Pathol. 1992;98(2):175–9.

    CAS  PubMed  Google Scholar 

  9. 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.

    PubMed  Google Scholar 

  10. Loy TS, Sharp SC, Andershock CJ, Craig SB. Distribution of CA 19-9 in adenocarcinomas and transitional cell carcinomas. An immunohistochemical study of 527 cases. Am J Clin Pathol. 1993;99(6):726–8.

    CAS  PubMed  Google Scholar 

  11. Li D, Xie K, Wolff R, Abbruzzese JL. Pancreatic cancer. Lancet. 2004;363(9414):1049–57.

    CAS  PubMed  Google Scholar 

  12. Weissmueller S, Manchado E, Saborowski M, Morris JP, Wagenblast E, Davis CA, et al. Mutant p53 drives pancreatic cancer metastasis through cell-autonomous PDGF receptor β signaling. Cell. 2014;157(2):382–94.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Blackford A, Serrano OK, Wolfgang CL, Parmigiani G, Jones S, Zhang X, et al. SMAD4 gene mutations are associated with poor prognosis in pancreatic cancer. Clin Cancer Res. 2009;15(14):4674–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Rochefort MM, Ankeny JS, Kadera BE, Donald GW, Isacoff W, Wainberg ZA, et al. Impact of tumor grade on pancreatic cancer prognosis: validation of a novel TNMG staging system. Ann Surg Oncol. 2013;20(13):4322–9.

    PubMed  Google Scholar 

  15. Schlitter AM, Segler A, Steiger K, Michalski CW, Jäger C, Konukiewitz B, et al. Molecular, morphological and survival analysis of 177 resected pancreatic ductal adenocarcinomas (PDACs): identification of prognostic subtypes. Sci Rep. 2017;7:41064.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Borazanci E, Millis SZ, Korn R, Han H, Whatcott CJ, Gatalica Z, et al. Adenosquamous carcinoma of the pancreas: molecular characterization of 23 patients along with a literature review. World J Gastrointest Oncol. 2015;7(9):132–40.

    PubMed  PubMed Central  Google Scholar 

  17. Hsu J-T, Yeh C-N, Chen Y-R, Chen H-M, Hwang T-L, Jan Y-Y, et al. Adenosquamous carcinoma of the pancreas. Digestion. 2005;72(2–3):104–8.

    PubMed  Google Scholar 

  18. Madura JA, Jarman BT, Doherty MG, Yum MN, Howard TJ. Adenosquamous carcinoma of the pancreas. Arch Surg. 1999;134(6):599–603.

    CAS  PubMed  Google Scholar 

  19. Boyd CA, Benarroch-Gampel J, Sheffield KM, Cooksley CD, Riall TS. 415 patients with adenosquamous carcinoma of the pancreas: a population-based analysis of prognosis and survival. J Surg Res. 2012;174(1):12–9.

    PubMed  Google Scholar 

  20. Brody JR, Costantino CL, Potoczek M, Cozzitorto J, McCue P, Yeo CJ, et al. Adenosquamous carcinoma of the pancreas harbors KRAS2, DPC4 and TP53 molecular alterations similar to pancreatic ductal adenocarcinoma. Mod Pathol. 2009;22(5):651–9.

    CAS  PubMed  Google Scholar 

  21. Basturk O, Khanani F, Sarkar F, Levi E, Cheng JD, Adsay NV. DeltaNp63 expression in pancreas and pancreatic neoplasia. Mod Pathol. 2005;18(9):1193–8.

    CAS  PubMed  Google Scholar 

  22. Fang Y, Su Z, Xie J, Xue R, Ma Q, Li Y, et al. Genomic signatures of pancreatic adenosquamous carcinoma (PASC). J Pathol. 2017;243(2):155–9.

    CAS  PubMed  Google Scholar 

  23. Mueller S, Engleitner T, Maresch R, Zukowska M, Lange S, Kaltenbacher T, et al. Evolutionary routes and KRAS dosage define pancreatic cancer phenotypes. Nature. 2018;554(7690):62–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Krasinskas AM, Moser AJ, Saka B, Adsay NV, Chiosea SI. KRAS mutant allele-specific imbalance is associated with worse prognosis in pancreatic cancer and progression to undifferentiated carcinoma of the pancreas. Mod Pathol. 2013;26(10):1346–54.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Agaimy A, Haller F, Frohnauer J, Schaefer I-M, Ströbel P, Hartmann A, et al. Pancreatic undifferentiated rhabdoid carcinoma: KRAS alterations and SMARCB1 expression status define two subtypes. Mod Pathol. 2015;28(2):248–60.

    CAS  PubMed  Google Scholar 

  26. Muraki T, Reid MD, Basturk O, Jang K-T, Bedolla G, Bagci P, et al. Undifferentiated carcinoma with osteoclastic giant cells of the pancreas: clinicopathologic analysis of 38 cases highlights a more protracted clinical course than currently appreciated. Am J Surg Pathol. 2016;40(9):1203–16.

    PubMed  PubMed Central  Google Scholar 

  27. Bergmann F, Esposito I, Michalski CW, Herpel E, Friess H, Schirmacher P. Early undifferentiated pancreatic carcinoma with osteoclastlike giant cells: direct evidence for ductal evolution. Am J Surg Pathol. 2007;31(12):1919–25.

    PubMed  Google Scholar 

  28. Mostafa ME, Erbarut-Seven I, Pehlivanoglu B, Adsay V. Pathologic classification of “pancreatic cancers”: current concepts and challenges. Chin Clin Oncol. 2017;6(6):59.

    PubMed  Google Scholar 

  29. Tan MC, Basturk O, Brannon AR, Bhanot U, Scott SN, Bouvier N, et al. GNAS and KRAS mutations define separate progression pathways in intraductal papillary mucinous neoplasm-associated carcinoma. J Am Coll Surg. 2015;220(5):845–854.e1.

    PubMed  PubMed Central  Google Scholar 

  30. Liszka L, Zielinska-Pajak E, Pajak J, Gołka D. Colloid carcinoma of the pancreas: review of selected pathological and clinical aspects. Pathology. 2008;40(7):655–63.

    CAS  PubMed  Google Scholar 

  31. Wilentz RE, Goggins M, Redston M, Marcus VA, Adsay NV, Sohn TA, 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Yamamoto H, Itoh F, Nakamura H, Fukushima H, Sasaki S, Perucho M, et al. Genetic and clinical features of human pancreatic ductal adenocarcinomas with widespread microsatellite instability. Cancer Res. 2001;61(7):3139–44.

    CAS  PubMed  Google Scholar 

  33. Goggins M, Offerhaus GJ, Hilgers W, Griffin CA, Shekher M, Tang D, et al. Pancreatic adenocarcinomas with DNA replication errors (RER+) are associated with wild-type K-ras and characteristic histopathology. Poor differentiation, a syncytial growth pattern, and pushing borders suggest RER+. Am J Pathol. 1998;152(6):1501–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Stauffer JA, Asbun HJ. Rare tumors and lesions of the pancreas. Surg Clin North Am. 2018;98(1):169–88.

    PubMed  Google Scholar 

  35. Su J-S, Chen Y-T, Wang R-C, Wu C-Y, Lee S-W, Lee T-Y. Clinicopathological characteristics in the differential diagnosis of hepatoid adenocarcinoma: a literature review. World J Gastroenterol. 2013;19(3):321–7.

    PubMed  PubMed Central  Google Scholar 

  36. Stamatova D, Theilmann L, Spiegelberg C. A hepatoid carcinoma of the pancreatic head. Surg Case Rep. 2016;2(1):78.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Chang JM, Katariya NN, Lam-Himlin DM, Haakinson DJ, Ramanathan RK, Halfdanarson TR, et al. Hepatoid carcinoma of the pancreas: case report, next-generation tumor profiling, and literature review. Case Rep Gastroenterol. 2016;10(3):605–12.

    PubMed  PubMed Central  Google Scholar 

  38. Kuo P-C, Chen S-C, Shyr Y-M, Kuo Y-J, Lee R-C, Wang S-E. Hepatoid carcinoma of the pancreas. World J Surg Oncol. 2015;13:185.

    PubMed  PubMed Central  Google Scholar 

  39. Rad R, Rad L, Wang W, Strong A, Ponstingl H, Bronner IF, et al. A conditional piggyBac transposition system for genetic screening in mice identifies oncogenic networks in pancreatic cancer. Nat Genet. 2015;47(1):47–56.

    CAS  PubMed  Google Scholar 

  40. Späth C, Nitsche U, Müller T, Michalski C, Erkan M, Kong B, et al. Strategies to improve the outcome in locally advanced pancreatic cancer. Minerva Chir. 2015;70(2):97–106.

    PubMed  Google Scholar 

  41. Paniccia A, Hosokawa PW, Schulick RD, Henderson W, Kaplan J, Gajdos C. A matched-cohort analysis of 192 pancreatic anaplastic carcinomas and 960 pancreatic adenocarcinomas: a 13-year North American experience using the National Cancer Data Base (NCDB). Surgery. 2016;160(2):281–92.

    PubMed  Google Scholar 

  42. Özdemir BC, Pentcheva-Hoang T, Carstens JL, Zheng X, Wu C-C, Simpson TR, et al. Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival. Cancer Cell. 2014;25(6):719–34.

    PubMed  PubMed Central  Google Scholar 

  43. Rhim AD, Oberstein PE, Thomas DH, Mirek ET, Palermo CF, Sastra SA, et al. Stromal elements act to restrain, rather than support, pancreatic ductal adenocarcinoma. Cancer Cell. 2014;25(6):735–47.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Apte MV, Park S, Phillips PA, Santucci N, Goldstein D, Kumar RK, et al. Desmoplastic reaction in pancreatic cancer: role of pancreatic stellate cells. Pancreas. 2004;29(3):179–87.

    CAS  PubMed  Google Scholar 

  45. Esposito I, Penzel R, Chaib-Harrireche M, Barcena U, Bergmann F, Riedl S, et al. Tenascin C and annexin II expression in the process of pancreatic carcinogenesis. J Pathol. 2006;208(5):673–85.

    CAS  PubMed  Google Scholar 

  46. Olive KP, Jacobetz MA, Davidson CJ, Gopinathan A, McIntyre D, Honess D, et al. Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science. 2009;324(5933):1457–61.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Erkan M, Michalski CW, Rieder S, Reiser-Erkan C, Abiatari I, Kolb A, et al. The activated stroma index is a novel and independent prognostic marker in pancreatic ductal adenocarcinoma. Clin Gastroenterol Hepatol. 2008;6(10):1155–61.

    PubMed  Google Scholar 

  48. Wang JP, Wu C-Y, Yeh Y-C, Shyr Y-M, Wu Y-Y, Kuo C-Y, et al. Erlotinib is effective in pancreatic cancer with epidermal growth factor receptor mutations: a randomized, open-label, prospective trial. Oncotarget. 2015;6(20):18162–73.

    PubMed  PubMed Central  Google Scholar 

  49. Knudsen ES, Vail P, Balaji U, Ngo H, Botros IW, Makarov V, et al. Stratification of pancreatic ductal adenocarcinoma: combinatorial genetic, stromal, and immunologic markers. Clin Cancer Res. 2017;23(15):4429–40.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Haeberle L, Steiger K, Schlitter AM, Safi SA, Knoefel WT, Erkan M, Esposito I. Stromal heterogeneity in pancreatic cancer and chronic pancreatitis [published online ahead of print, 2018 May 12]. Pancreatology. 2018;S1424-3903(18)30109–1. https://doi:10.1016/j.pan.2018.05.004.

  51. Fujita T, Nakagohri T, Gotohda N, Takahashi S, Konishi M, Kojima M, et al. Evaluation of the prognostic factors and significance of lymph node status in invasive ductal carcinoma of the body or tail of the pancreas. Pancreas. 2010;39(1):e48–54.

    PubMed  Google Scholar 

  52. Moffitt RA, Marayati R, Flate EL, Volmar KE, Loeza SGH, Hoadley KA, et al. Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma. Nat Genet. 2015;47(10):1168–78.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Collisson EA, Sadanandam A, Olson P, Gibb WJ, Truitt M, Gu S, et al. Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy. Nat Med. 2011;17(4):500–3.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Bailey P, Chang DK, Nones K, Johns AL, Patch A-M, Gingras M-C, et al. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature. 2016;531(7592):47–52.

    CAS  Google Scholar 

  55. Puleo F, Nicolle R, Blum Y, Cros J, Marisa L, Demetter P, et al. Stratification of pancreatic ductal adenocarcinomas based on tumor and microenvironment features. Gastroenterology. 2018;155(6):1999–2013.e3.

    PubMed  Google Scholar 

  56. Muckenhuber A, Berger AK, Schlitter AM, Steiger K, Konukiewitz B, Trumpp A, et al. Pancreatic ductal adenocarcinoma subtyping using the biomarkers hepatocyte nuclear factor-1A and cytokeratin-81 correlates with outcome and treatment response. Clin Cancer Res. 2018;24(2):351–9.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Institute of Pathology, Heinrich-Heine University & University Hospital of Düsseldorf, Düsseldorf, Germany

    Luisa Ingenhoff, Lena Häberle & Irene Esposito

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  1. Luisa Ingenhoff
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  2. Lena Häberle
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  3. Irene Esposito
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Correspondence to Irene Esposito .

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Editors and Affiliations

  1. Department of Visceral, Vascular and Endocrine Surgery, University Hospital Halle (Saale), Halle (Saale), Sachsen-Anhalt, Germany

    Christoph W. Michalski

  2. Department of Internal Medicine I, University Hospital Halle (Saale), Halle (Saale), Sachsen-Anhalt, Germany

    Jonas Rosendahl

  3. Department of Internal Medicine I, University Hospital Halle (Saale), Halle (Saale), Sachsen-Anhalt, Germany

    Patrick Michl

  4. Department of Visceral, Vascular and Endocrine Surgery, University Hospital Halle (Saale), Halle (Saale), Sachsen-Anhalt, Germany

    Jörg Kleeff

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Ingenhoff, L., Häberle, L., Esposito, I. (2020). Subtypes of Pancreatic Adenocarcinoma. In: Michalski, C., Rosendahl, J., Michl, P., Kleeff, J. (eds) Translational Pancreatic Cancer Research. Molecular and Translational Medicine. Humana, Cham. https://doi.org/10.1007/978-3-030-49476-6_1

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  • DOI: https://doi.org/10.1007/978-3-030-49476-6_1

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