Vol. 6, 551-552, July 1997 Cancer Epidemiology, Biomarkers & Prevention 551
Short Communication
Comparison of Two Enzyme-linked Immunosorbent Assay Tests for
Diagnosis of Helicobacter pylon Infection in China
Frank D. Groves,2 Lian Zhang, Ji-you Li,
Weicheng You, Yun-sheng Chang, Lei Zhao,
Wei-dong Liu, Charles S. Rabkin,
Guillermo I. Perez-Perez, Martin J. Blaser, and
Mitchell H. Gall
Division of Cancer Epidemiology and Genetics, National Cancer Institute,
NIH, Bethesda, Maryland 20892-7368 [F. D. G., W-c. Y., C. S. R., M. H. G.];
Beijing Institute for Cancer Research and School of Oncology, Beijing
Medical University, Beijing, People’s Republic of China 100034 [L. Thang,
J-y. L., W-c. Y., L. Thao]; Weifang Medical Institute, Weifang, Shandong,
People’s Republic of China 261041 [Y-s. C.]; Linqu Public Health Bureau,
Linqu, Shandong, People’s Republic of China 262600 [W-d. L.}; and
Vanderbilt University Medical Center, Nashville, Tennessee 37232-2605
[G. I. P-P., M. J. B.]
Abstract
An ELISA based on a pool of United States strains of
Helicobacterpylori was compared with a newly developed
ELISA based on a pool of Chinese strains. Both assays were
tested using sera from 132 Chinese study subjects with
biopsy-proven H. pylon infection. Using cutpoints designed
to yield equal specificities of 94.9% in an uninfected control
population, the sensitivity of the Chinese assay was 100.0%,
compared to 97.7% for the United States assay (P = 0.25 by
McNemar test). These results suggest that a H. pylon assay
based on pooled antigens from United States strains will
perform as well in the rural Chinese population as one
based on antigens from Chinese strains.
Introduction
The rural county of Linqu in Shandong Province in northeast
China has among the highest age-adjusted stomach cancer
mortality rates in the world (1). A population-based endoscopic
screening program in Linqu in 1989 revealed a high prevalence
of chronic atrophic gastritis (98.1%), intestinal metaplasia
(52.8%), and dysplasia (20.4%; Ref. 2). These lesions are
believed to be steps in the progression from normal gastric
epithelium to gastric adenocarcinoma of the intestinal type (3).
The curved bacillus Helicobacter pylon has been shown to
cause chronic atrophic gastritis (4, 5), which may progress to
intestinal metaplasia. The seroprevalence of H. pylon infection
in Linqu is 72% overall, and the seroprevalence is highest
among those with most severe chronic atrophic gastritis (6).
It was reported previously (7) that a commercial H. pylon
Received 1 1/1/96; revised 2/20/97; accepted 2/24/97.
The costs of publication of this article were defrayed in part by the payment of
page charges. This article must therefore be hereby marked advertisement in
accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 Supported in part by Grant R0l-CA-58834 from the National Cancer Institute.
2 To whom requests for reprints should be addressed, at Biostatistics Branch,
Room 431-C, Epidemiology and Biostatistics Program, Division of Cancer Ep-
idemiology and Genetics, National Cancer Institute, 6130 Executive Boulevard,
MSC 7368, Bethesda, MD 20892-7368.
assay based on United States strains performed poorly (sensi-
tivity, 85%; specificity, 66%) in a seroprevalence survey in Thai-
land, and that a new assay based on indigenous Thai strains of H.
pylon performed better (sensitivity, 98%; specificity, 76%). This
result raised concerns that comparison of studies in different coun-
tries would be problematic and that it would be necessary to
develop specific assays for each country. We developed a new
serological test based on indigenous Chinese strains of H. pyloni
for use in a clinical trial in rural China (6). We report here the
results of a validation study to compare this new assay with a
widely used assay based on United States H. pyloni strains.
Materials and Methods
Study Subjects and Specimens. Subjects resided in the rural
Chinese village of Bei Duan in Linqu County in Shandong
Province, a population at high risk of stomach cancer. There
were 292 villagers ages 35-64, of whom 277 were recruited for
the study. 263 of these completed the initial interview; two of
these failed the physical examination. Of the remaining 261,
239 (91.6%) underwent endoscopy in 1989, with biopsies taken
from seven standard sites in the stomach. Twenty subjects with
fewer than seven biopsies were excluded, leaving 219 subjects
who had a full set of seven biopsies. Biopsies were preserved
in 10% neutral buffered formalin, embedded in paraffin, and
sectioned at the Beijing Institute for Cancer Research. Biopsies
were reviewed by a panel of three senior pathologists at the
Beijing Institute for Cancer Research and interpreted according
to the protocol of the Chinese Association of Gastric Cancer
(8). The presence or absence of superficial gastritis, chronic
atrophic gastritis, intestinal metaplasia, and dysplasia was re-
corded for each biopsy; diagnostic criteria were published pre-
viously (2). Each biopsy was given an overall diagnosis based
on the most advanced lesion, and each subject was assigned a
global diagnosis based on the most advanced lesion among any
of the seven biopsies.
An additional unstained slide from each biopsy was
stained with Lennert’s Giemsa and read by one of us (F. D. G.).
Any biopsy in which curved bacilli were seen overlying the
gastric mucosa was rated as positive for H. pyloni infection, and
any case with at least one out of seven positive biopsies was
rated as a positive case. All slides from negative cases and a
sampling of positive slides were submitted for expert review.
Serology. Gastric biopsies were cultured from 20 of the Chi-
nese subjects; strains from five of seven H. pyloni-infected
subjects were pooled to provide antigenic material for serology.
The “Chinese” antigen, derived from the five H. pyloni isolates,
was prepared in essentially the same way as the “United States”
antigen (9). The five strains were grown on blood agar plates
and then resuspended in distilled water. The cell suspensions
ware sonicated six times for 30 s each, and protein determina-
tion was performed by bicinchonic acid assay (Pierce Chemical
Co., Rockford, IL) prior to pooling the solutions. Microtiter
plates were prepared using 1 pg total protein per well. Sera
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