pancreatic ductal adenocarcinoma

WKP

Definition: Pancreatic adenocarcinoma is the fifth leading cause of cancer death with a 5-year survival rate of less than 5%.

Images

 Histopathology of pancreatic ductal adenocarcinoma

• https://commons.wikimedia.org/wiki/File:Histopathology_of_pancreatic_ductal_adenocarcinoma.jpg

 Histopathology of pancreatic adenocarcinoma with treatment effect after chemotherapy, showing fibroelastotic tissue with scattered tumor cells.

• https://commons.wikimedia.org/wiki/File:Histopathology_of_pancreatic_adenocarcinoma_with_treatment_effect.jpg

 Micrograph of loose, moderate and dense desmoplastic stroma in pancreatic ductal adenocarcinoma

• https://commons.wikimedia.org/wiki/File:Micrograph_of_loose,_moderate_and_dense_desmoplastic_stroma_in_pancreatic_ductal_adenocarcinoma.jpg

Digital cases

 JRC:10443 : cutaneous metastasis of a pancreatic adenocarcinoma.

Molecular biology

The most prevalent genetic alterations were in KRAS (78% of patients), TP53 (tumor protein p53) (25%), and SMAD4 (SMAD family member 4) (8%). (26378065)

 genic inactivations by somatic mutations

• p53 (TP53) at 17p13.1 (MIM.191170) (25%)
• MADH4 (DPC4 or SMAD4) at 18q21.1 (MIM.600993) (8%)
• p16 (CDKN2A or MTS1) at 9p21 (MIM.600160)
• ACVR1B at 12q13 (MIM.601300)

 genic activation

• K-RAS (KRAS2) at 12q12.1 (MIM.190070) (78%)

 KRAS/TP53-associated pancreatic adenocarcinoma

Susceptibility loci

 21q21.3 (22158540)
 5p13.1 (22158540)
 21q22.3 (22158540)
 22q13.32 (22158540)
 10q26.11 (22158540)

Familial predisposition

Familial pancreatic cancer (FPC) represents 9% of PC, and the risk of malignancy in kindred does not appear to be confined to the pancreas. (25313458)

Genetic risk factors are believed to play a major role. Approximately 10% of PC is estimated to have familial inheritance.

Several germline mutations have been found to be involved in hereditary forms of PC, including both familial PC (FPC) and PC as one of the manifestations of a hereditary cancer syndrome or other hereditary conditions.

Candidate genes have been described and patients considered for screening programs under research protocols should first be tested for presence of germline mutations in the BRCA2, PALB2 and ATM genes. In specific PC populations, including in Italy, hereditary cancer predisposition genes such as CDKN2A also explain a considerable fraction of FPC. (25152581)

Candidate genes: BRCA2, PALB2, ATM, CDKN2A. (25152581)

See: familial pancreatic cancer

Links

 Nomenclature for Classification of Duct Lesions in the Pancreas (NCI, 1999) at Hopkins

Videos

 Pancreatic adenocarcinoma by Washington Deceit (1)

• http://www.youtube.com/v/lkS2Ug8_q8s

 Pancreatic adenocarcinoma by Washington Deceit (2)

• http://www.youtube.com/v/ssD7MtdSbKc

Open references

 Variant Profiling of Candidate Genes in Pancreatic Ductal Adenocarcinoma.
Huang J, Löhr JM, Nilsson M, Segersvärd R, Matsson H, Verbeke C, Heuchel R, Kere J, Iafrate AJ, Zheng Z, Ye W.
Clin Chem. 2015 Nov;61(11):1408-16. doi : 10.1373/clinchem.2015.238543
PMID: 26378065 Free

Reviews

 Welsch T, Kleeff J, Friess H. Molecular pathogenesis of pancreatic cancer: advances and challenges. Curr Mol Med. 2007 Aug;7(5):504-21. PMID: 17691965

 Karhu R, Mahlamaki E, Kallioniemi A. Pancreatic adenocarcinoma — genetic portrait from chromosomes to microarrays. Genes Chromosomes Cancer. 2006 Aug;45(8):721-30. PMID: 16688744

 Soto JL, Barbera VM, Saceda M, Carrato A. Molecular biology of exocrine pancreatic cancer. Clin Transl Oncol. 2006 May;8(5):306-12. PMID: 16760004

 Laheru D, Jaffee EM. Immunotherapy for pancreatic cancer - science driving clinical progress. Nat Rev Cancer. 2005 Jun;5(6):459-67. PMID: 15905855

 Lynch HT, Deters CA, Lynch JF, Brand RE. Familial pancreatic carcinoma in Jews. Fam Cancer. 2004;3(3-4):233-40. PMID: 15516847

 Hilgers W, Rosty C, Hahn SA. Molecular pathogenesis of pancreatic cancer. Hematol Oncol Clin North Am. 2002 Feb;16(1):17-35, v. PMID: 12063826

 Bardeesy N, DePinho RA. Pancreatic cancer biology and genetics. Nat Rev Cancer. 2002 Dec;2(12):897-909. PMID: 12459728

References

 Genome-wide association study identifies five loci associated with susceptibility to pancreatic cancer in Chinese populations. Wu C, Miao X, Huang L, Che X, Jiang G, Yu D, Yang X, Cao G, Hu Z, Zhou Y, Zuo C, Wang C, Zhang X, Zhou Y, Yu X, Dai W, Li Z, Shen H, Liu L, Chen Y, Zhang S, Wang X, Zhai K, Chang J, Liu Y, Sun M, Cao W, Gao J, Ma Y, Zheng X, Cheung ST, Jia Y, Xu J, Tan W, Zhao P, Wu T, Wang C, Lin D. Nat Genet. 2011 Dec 11;44(1):62-6. PMID: 22158540