TITLE:
Adenocarcinomas of the gallbladder from United States patients demonstrate less frequent molecular change for several genetic markers than other intra-abdominal cancers
AUTHORS:
Peter Zauber, Stephen Marotta, Marlene Sabbath-Solitare
KEYWORDS:
Gallbladder Carcinoma; Molecular Genetic Changes; KRAS Mutation; GNAS Mutation; BRAF Mutation; Microsatellite Instability; Loss of Heterozygosity
JOURNAL NAME:
Open Journal of Gastroenterology,
Vol.3 No.8,
December
26,
2013
ABSTRACT:
Context: The incidence of gallbladder cancer is
quite low in the US, with an estimate (2013) for new cases of less than 10,000.
The rarity suggests a possible shared molecular pathology that might facilitate
a greater understanding of this tumor. Objective: We wished to assess the
molecular genetic profile of this tumor, particularly KRAS gene mutations, which are frequent in tumors associated with
chronic inflamemation elsewhere within the abdomen. Design: We ascertained 25
cases of gallbladder adenocarcinoma from our pathology department records for
2000-2012. PCR based techniques were used to evaluate the DNA for loss of
heterozygosity of the APC and DCC genes; for point mutations in the KRAS gene, codons 12 and 13; for point
mutation in the BRAF gene, codon 600;
for point mutation in the GNAS gene,
codon 201; and for microsatellite instability. Results: Patients included 5
males and 20 females. Approximately three-quarters of cases were associated
with gallstones, inflammation and dysplasia. Microsatellite instability and GNAS mutation, both present in just 4%
of cases, and BRAF mutation present
in no cases, do not appear to be significant parts of carcinogenesis of gallbladder
carcinoma. We detected a KRAS gene
mutation in only 8% of the cases. Loss of heterozygosity for the APC was detected in 16.7% of informative
cases; and for the DCC gene, in 34.8%
of informative cases. Conclusions: Many molecular genetic changes frequently
seen with tumors arising from other intra-abdominal organs are infrequent in this tumor type. In
particular, KRAS mutations were
uncommon, in contra-distinction to other malignant tumors developing in the
setting of chronic inflammation/infection.