Adenocarcinoma of the Esophagus

 

Epidemiology and Etiology:

·       > 40y usually

·       Median 50s

·       M > F

·       Whites > blacks in US

·       ~50% of esophageal CA in the US

·       Barrett esophagus background (majority)

·       10% lifetime risk in Barrett

·       Tobacco

·       Obesity

·       H. pylori maybe (controversial)

·       No association with alcohol

 

Common sites:

·        

 

Gross features:

·       EGJ is defined as where the tubular esophagus meets the stomach, not as where the SCJ is

 

Histologic features:

·       Mucin-producing (most)

·       Intestinal-type (most)

·       Signet-ring type

·       Small-cell type

·       Grade:

·       1: > 95% glands

·       2: 50-95% glands

·       3: 49% or less glands

·       4: cannot be categorized as squamous or adenocarcinoma, also small cell CA (not typically graded)

·       Response to Treatment (tumour regression score):

·       No viable cancer cells (complete response): 0

·       Single cells or rare small groups of cancer cells (near complete response): 1

·       Residual cancer with evident tumour regression, but more than single cells or rare small groups of cancer cells (partial response): 2

·       Extensive residual cancer with no evident tumour regression (poor or no response): 3

·       Pools of acellular mucin should not be interpreted as residual tumour

 

Immunophenotype:

Marker:

Sensitivity:

Specificity:

 

 

 

 

Molecular features:

·       TP53 inactivation (40-80%) (increases with grade)

·       Mutation (poor prognosis)

·       LOH

·       CDKN2A (p16) inactivation (80%) (early)

·       Promoter methylation

·       LOH

·       CCND1 overexpression (90%)

·       EGFR overexpression (30-60%)

·       Rarely mutation

·       KRAS mutation (21%)

·       PTGS2 (COX2) upregulation (79%) (poor prognosis)

·       ERBB2 overexpression (poor prognosis)

·       Amplification of c-ERB-B2 (HER2/neu) (poor prognosis)

·       AMACR overexpression (72-96%)

·       IMP3

·       Chromosomal aberrations

·       Tetraploidy (poor prognosis)

·       aneuploidy

·       Chromosome 4 amplification

·       Nuclear translocation of beta-catenin

·       Gains:

·       8q (MYC) gain

·       20q

·       Losses:

·       FHIT (3p)

·       4q

·       APC (5q)

·       SMAD4, DCC (18q)

·       Familial polymorphisms:

·       GSTP1

·       GSTM1

·       GSTT1

·       XPC

·       CCND1

·       PTGS2/COX2

·       EGF

·       Matrix metalloprotein genes

·       ERCC2/XPD

·       XRCC1

·       NQO1 TT

 

Other features:

·       Poor prognosis

·       5y survival < 20% overall

·        

 

References:

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

·       CAP protocol 2016