LWBK1006-20 LWW-Govindan-Review December 12, 2011 19:4
Chapter 20•Cancer of the Gastrointestinal Tract 239mutation even without gross mucosal abnormalities on endoscopic exam-
ination of the stomach. Hereditary nonpolyposis colon cancer (HNPCC)
involves germ line mutations of DNA mismatch repair genes. Gastric ade-
nocarcinoma may be observed in families with HNPCC.Answer 20.1.6. The answer is D.
A reasonably prevalent alteration is microsatellite instability, the result of
changes in DNA mismatch repair genes (PPOTable 39.1.1). Microsatel-
lite instability and associated alterations of the TGF-b II receptor, IGFRII,
BAX, E2F-4, hMSH3, and hMSH6 genes are found in a subset of gastric
carcinomas. Microsatellite instability has been found in 13% to 44% of
sporadic gastric carcinomas. A high degree of microsatellite instability
occurs in gastric cancers of the intestinal type, reduced involvement of
lymph nodes, enhanced lymphoid infiltration, and better prognosis. This
is reminiscent of colon cancers associated with HNPCC. The p53 tumor
suppressor gene is consistently altered in most gastric cancers. In a study
of the promoter region of p16 in gastric cancers, a significant number
(41%) exhibited CpG island methylation. Many cases with hypermethy-
lation of promoter regions displayed the phenotype with a high degree of
microsatellite instability and multiple sites of methylation, including the
hMLH1 promoter region. Many sporadic diffuse gastric cancers display
altered E-cadherin. E-cadherin may be downregulated in gastric carcino-
genesis (especially diffuse gastric adenocarcinoma) by point mutation,
allelic deletion, or promoter methylation. In addition, during epithelial–
mesenchymal transition, E-cadherin transcription can be silenced by tran-
scriptional factors such as Snail and Slug.Answer 20.1.7. The answer is B.
Median survival after esophagectomy for patients with localized dis-
ease is 15 to 18 months with a 5-year overall survival rate of 20% to
25%. Patterns of failure after esophagectomy suggest that both location
of tumor and histologic type may influence the distribution of recur-
rence. In patients with cancers of the upper and middle thirds of the
esophagus, which are predominately squamous cell carcinomas, locore-
gional recurrence predominates over distant recurrence. In patients with
lesions of the lower third, where adenocarcinomas are more frequently
located, distant recurrence is more common. Treatment failure patterns
after definitive chemoradiotherapy without surgical resection reveal that
concurrent administration of chemotherapy and radiotherapy provides
better local control than radiotherapy alone, and that the administration
of chemotherapy may reduce systemic recurrence; however, long-term
follow-up of both randomized and nonrandomized patients treated with
primary chemoradiotherapy failed to indicate a clear reduction in distant
disease recurrence compared with radiation therapy alone. Although the
addition of surgery further reduces local failure from 45% to 32%, it
does not diminish systemic recurrence and, in fact, may enhance it by
allowing patients to manifest distant disease because they do not suc-
cumb to locoregional failure. Two recent prospective randomized tri-
als evaluating primary chemoradiotherapy alone or chemoradiotherapy