Background-Helicobacter pylori, the main cause of chronic gastritis, is a class I gastric carcinogen. Chronic gastritis progresses to cancer through atrophy, metaplasia, and dysplasia. Precancerous phenotypic expression is generally associated with acquired genomic instability. Aim-To evaluate the eVect of H pylori infection and its eradication on gastric histology, cell proliferation, DNA status, and oncogene expression. Methods/Subjects-Morphometric and immunohistochemical techniques were used to examine gastric mucosal biopsy specimens from eight controls, 10 patients with H pylori negative chronic gastritis, 53 with H pylori positive chronic gastritis, and 11 with gastric cancer. Results-All patients with chronic gastritis were in a hyperproliferative state related to mucosal inflammation, regardless of H pylori infection. Atrophy was present in three of 10 patients with H pylori negative chronic gastritis and in 26 of 53 with H pylori positive chronic gastritis, associated in 18 with intestinal metaplasia. DNA content was abnormal in only 11 patients with atrophy and H pylori infection; eight of these also had c-Myc expression, associated in six cases with p53 expression. Fifty three patients with H pylori positive chronic gastritis were monitored for 12 months after antibiotic treatment: three dropped out; infection was eradicated in 45, in whom cell proliferation decreased in parallel with the reduction in gastritis activity; atrophy previously detected in 21/45 disappeared in five, regressed from moderate to mild in nine, and remained unchanged in seven; complete metaplasia disappeared in 4/14, and markers of genomic instability disappeared where previously present. In the five patients in whom H pylori persisted, atrophy, metaplasia, dysplasia, and markers of genomic instability remained unchanged. Conclusions-Chronic H pylori infection seems to be responsible for genomic instability in a subset of cases of H pylori positive chronic atrophic gastritis; eradication of H pylori infection can reverse inflammation and the related atrophy, metaplasia, and genomic instability. (Gut 1999;44:789-799)

The expression of growth factors, such as transforming growth factor a (TGFa), amphiregulin (AR) and CRIPTO, a type-I tyrosine-kinase growth factor receptor (erbB-2), and a tumor-suppressor gene (p53). that have been implicated in the development and/or the progression of breast cancer, was evaluated by immunohistochemistry in I00 human primary infiltrating breast carcinomas (IBC). AR and CRIPTO imrnunoreactivity was also assessed in 55 human breast ductal carcinomas in situ (DCIS). Within the I00 IBC, 80,50,73, 17, and 34 tumors expressed moderate to high levels of TGFol, AR, CRIPTO, erb6-2, and p53 respectively. In addition, AR and CRIPTO immunoreactivity were found in I I and in 26 out of 55 DCIS respectively. In contrast, only 4, 3, and 2 out of 10 normal mammary-gland samples were weakly positive for TGFol, AR, and CRIPTO expression, respectively, whereas none was positive for erbB-2 or p53. Within the I00 IBC, expression of erb6-2 significantly correlated with high histologic and nuclear grading, with high growth fraction, and with estrogen-receptor(ER)-and progesterone-receptor(PgR)-negative tumors. A statistically rignificant correlation was also observed between p53 expression and high histologic grading, high growth fraction, and PgRnegative tumors. In contrast, no significant correlations were found between TGFol, AR, and CRIPTO imrnunoreactivity and various clinicopathological parameters, with the exception of a positive correlation between TGFa and ER expression. These data demonstrate that TGFol, AR, and CRIPTO expression are significantly increased in malignant mammary epithelium relative to normal epithelium. In particular, the differential expression of CRIPTO may serve as a potential tumor marker for breast carcinogenesis.o 1996 Wilq-Liss, Inc.

SUMMARYBackground: Histology is the gold standard for diagnosis of atrophy but is hampered by observer variation. A reliable method to overcome this issue is morphometric analysis of gastric mucosa. Serum pepsinogens and gastrin have been proposed in the diagnostic work-up of gastric atrophy although diagnostic accuracy of these tests is considered unsatisfactory. Aim: To evaluate the diagnostic accuracy of gastric serum profile in relation both to morphological and morphometric diagnosis of gastric atrophy. Methods: Ninety-four dyspeptic out-patients underwent upper endoscopy and evaluation of serum levels of PGI, PGII and 17-gastrin. Diagnostic accuracy of gastric

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