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: |
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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