Squamous Cell Carcinoma of the Esophagus

Epidemiology and Etiology:

· > 50y usually

· M > F

· Geography – higher incidence in:

· Iran

· Central China

· South Africa

· Southern Brazil

· Puerto Rico

· Eastern Europe

· Blacks > whites in US

· HPV

· More commonly found in high-incidence regions

· Infrequent in the US

· Associated factors:

· Diet:

· Vitamin deficiencies (A, C, riboflavin, thiamine, pyridoxine)

· Trace element deficiencies (zinc, molybdenum)

· Fungal contamination

· Nitrites / nitrosamines

· Betel nut chewing

· Lifestyle

· Burning hot beverages or food

· Alcohol

· Tobacco

· Methylating nitroso compounds

· Urban environment

· Esophageal disorders:

· Long-standing esophagitis

· Achalasia

· Plummer-Vinson syndrome

· Genetic predisposition:

· Celiac (long-standing)

· Ectodermal dysplasia

· Epidermolysis bullosa

· Racial predisposition

Common sites:

· 20% upper third

· 50% middle third

· 30% lower third

Gross features:

·

Histologic features:

·

Immunophenotype:

Marker:

Sensitivity:

Specificity:

Molecular features:

· P53 point mutations (> 50%)

· Early event, sometimes detectable in intraepithelial neoplasia

· Nuclear accumulation of p53 (poor prognosis in some studies)

· CDKN2A (p16INK4A) inactivation (advanced cancers)

· Deletion

· methylation

· amplifications:

· CCND1 (20-40%)

· MYC

· EGFR

· FGF4

· FGF6

· FHIT inactivation (3p14)

· Methylation

· TOC locus deletion (17q25)

· DLEC1 and DEC1 deletion (3p21.3 and 9q32)

· LRP1B and CRABP1 inactivation

· Genetic

· epigenetic

· Note that KRAS and APC mutations are rare

· Aneuploidy (55-95%) (poor prognosis compared to diploidy)

· Potentially prognostic in some studies:

· Growth factors and their receptors

· Proto-oncogenes (ERBB2, FGF3/INT2)

· Cell-cycle regulators (cyclin D1)

· Tumour suppressor genes

· Redox defence system components (metallothionein and heat-shock proteins)

· E-cadherin

· VEGF

· Matrix proteinases

· Familial esophageal CA:

· Non-epidermolytic palmoplantar keratoderma (NEPPK) (tylosis)

· TOC locus (tylosis oesophageal cancer) at 17q25

· Promoter of FLJ22341

· CYGB gene (unknown function)

· Downregulated in tylosis and sporadic cancers

· ASDH1B1 and ALDH2 polymorphisms (Asians)

Other features:

· Poor prognosis:

· 9% 5-year survival overall

· 25% in those with “curative” surgery

· 75% in superficial SCC

References:

· WHO Classification of Tumours of the Digestive System (2010)