Epigenetics and pancreatic cancer: Pathophysiology and novel treatment aspects

Table 1 Histomorphologic subtypes of pancreatic cancer related to their genetic/epigenetics and possible prognostic characteristics

Variant (source)	Morphology	Genetics/epigenetics	Prognosis
MC	Well defined pushing border, syncytial growth pattern, and poorly differentiated cancer cells	Germline or somatic mutations as well as epigenetic silencing by promoter methylation of mismatch repair genes MLH1 and MSH2	BetterMC: Overall 2- and 5-yr survival rate of 29% and 13%[23]CC: 2-yr and 5-yr survival rate of 70% and 57%[153]
CC	Suspension of well-differentiated cancer cells in extracellular mucin pools (at least 80%)	Unknown
AC	Combination of glandular and squamous (at least 30%) components	K-RAS2 mutations, inactivation of CDKN2A/p16, SMAD4/DPC4 and TP53	WorseAC/UC: Median survival of 5 mo after resection[154,155]
UC	Noncohesive cancer, lacking histological features of differentiation	K-RAS2 gene mutations, loss of E-cadherin protein expression (promoter hypermethylation)
		Expression of L1CAM, COX2, and EGFR
		Subtype with osteoclast-like giant cells shows mutations like noninvasive precursor lesions

MC: Medullary carcinoma; CC: Colloid carcinoma; AC: Adenosquamous carcinoma; UC: Undifferentiated carcinoma; COX: Cyclooxygenase; L1CAM: L1 cell adhesion molecule; EGFR: Epidermal growth factor receptor; MSH2: MutS homolog 2.