Premorphological alterations in gastric mucosa in patients with gastric cancer: hypoxia level assessed by 31P NMR spectroscopy
The aim of this study was to detect the hypoxic status in adjacent histologically uninvolved gastric mucosa in gastric cancer (GC) patients. Patients and Methods: 50 naïve patients with primary GC, and one patient with stomach ulcer (gastric mucosa was used as control) were enrolled into the study....
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| Zitieren: | Premorphological alterations in gastric mucosa in patients with gastric cancer: hypoxia level assessed by 31P NMR spectroscopy / L. Bubnovskaya, D. Osinsky, V. Trachevsky, L. Naleskina, A. Kovelskaya, L. Gumenyuk // Experimental Oncology. — 2014. — Т. 36, № 4. — С. 271-275. — Бібліогр.: 31 назв. — англ. |
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nasplib_isofts_kiev_ua-123456789-1453862025-02-23T20:09:49Z Premorphological alterations in gastric mucosa in patients with gastric cancer: hypoxia level assessed by 31P NMR spectroscopy Bubnovskaya, L. Osinsky, D. Trachevsky, V. Naleskina, L. Kovelskaya, A. Gumenyuk, L. Original contributions The aim of this study was to detect the hypoxic status in adjacent histologically uninvolved gastric mucosa in gastric cancer (GC) patients. Patients and Methods: 50 naïve patients with primary GC, and one patient with stomach ulcer (gastric mucosa was used as control) were enrolled into the study. The tumor and mucosa samples of stomach (without muscularis and serosa layers) in patients with GC were obtained immediately after operation. Assessment of the hypoxia level has been provided using 31P NMR spectroscopy in tissue perchloric acid extracts. Mucosa was examined by convenient histological method. Obtained results were analyzed statistically. Results: It was shown that gastric mucosa in 52% of patients with GC is under different levels of hypoxia, among them 23% of mucosa is under severe hypoxia (PME/Pi < 1.0) with average mean of PME/Pi 0.89 ± 0.04. It was revealed that there are definite associations between the hypoxia in mucosa tissue and pT as well as pN categories and G grade and stage of disease but not with M category. Overall survival of patients with gastric mucosa characterized by severe and mild hypoxia was significantly poorer as compared to that of patients with gastric mucosa with satisfactory oxygenation (p = 0.0035). Conclusion: Gastric mucosa uninvolved in tumor process is characterized by hypoxia in 52% of GC patients; severe hypoxia of mucosa was detected in 23% of patients having hypoxic mucosa. It was suggested that biochemical alterations in tissue surrounding tumor node may precede morphological ones. Key Words: gastric cancer, mucosa, hypoxia. This research was supported by the National Academy of Sciences of Ukraine (Grants no. 2.2.5.309 and no. 2.2.5.365). 2014 Article Premorphological alterations in gastric mucosa in patients with gastric cancer: hypoxia level assessed by 31P NMR spectroscopy / L. Bubnovskaya, D. Osinsky, V. Trachevsky, L. Naleskina, A. Kovelskaya, L. Gumenyuk // Experimental Oncology. — 2014. — Т. 36, № 4. — С. 271-275. — Бібліогр.: 31 назв. — англ. 1812-9269 https://nasplib.isofts.kiev.ua/handle/123456789/145386 en Experimental Oncology application/pdf Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
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Original contributions Original contributions Bubnovskaya, L. Osinsky, D. Trachevsky, V. Naleskina, L. Kovelskaya, A. Gumenyuk, L. Premorphological alterations in gastric mucosa in patients with gastric cancer: hypoxia level assessed by 31P NMR spectroscopy Experimental Oncology |
| description |
The aim of this study was to detect the hypoxic status in adjacent histologically uninvolved gastric mucosa in gastric cancer (GC) patients. Patients and Methods: 50 naïve patients with primary GC, and one patient with stomach ulcer (gastric mucosa was used as control) were enrolled into the study. The tumor and mucosa samples of stomach (without muscularis and serosa layers) in patients with GC were obtained immediately after operation. Assessment of the hypoxia level has been provided using 31P NMR spectroscopy in tissue perchloric acid extracts. Mucosa was examined by convenient histological method. Obtained results were analyzed statistically. Results: It was shown that gastric mucosa in 52% of patients with GC is under different levels of hypoxia, among them 23% of mucosa is under severe hypoxia (PME/Pi < 1.0) with average mean of PME/Pi 0.89 ± 0.04. It was revealed that there are definite associations between the hypoxia in mucosa tissue and pT as well as pN categories and G grade and stage of disease but not with M category. Overall survival of patients with gastric mucosa characterized by severe and mild hypoxia was significantly poorer as compared to that of patients with gastric mucosa with satisfactory oxygenation (p = 0.0035). Conclusion: Gastric mucosa uninvolved in tumor process is characterized by hypoxia in 52% of GC patients; severe hypoxia of mucosa was detected in 23% of patients having hypoxic mucosa. It was suggested that biochemical alterations in tissue surrounding tumor node may precede morphological ones. Key Words: gastric cancer, mucosa, hypoxia. |
| format |
Article |
| author |
Bubnovskaya, L. Osinsky, D. Trachevsky, V. Naleskina, L. Kovelskaya, A. Gumenyuk, L. |
| author_facet |
Bubnovskaya, L. Osinsky, D. Trachevsky, V. Naleskina, L. Kovelskaya, A. Gumenyuk, L. |
| author_sort |
Bubnovskaya, L. |
| title |
Premorphological alterations in gastric mucosa in patients with gastric cancer: hypoxia level assessed by 31P NMR spectroscopy |
| title_short |
Premorphological alterations in gastric mucosa in patients with gastric cancer: hypoxia level assessed by 31P NMR spectroscopy |
| title_full |
Premorphological alterations in gastric mucosa in patients with gastric cancer: hypoxia level assessed by 31P NMR spectroscopy |
| title_fullStr |
Premorphological alterations in gastric mucosa in patients with gastric cancer: hypoxia level assessed by 31P NMR spectroscopy |
| title_full_unstemmed |
Premorphological alterations in gastric mucosa in patients with gastric cancer: hypoxia level assessed by 31P NMR spectroscopy |
| title_sort |
premorphological alterations in gastric mucosa in patients with gastric cancer: hypoxia level assessed by 31p nmr spectroscopy |
| publisher |
Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| publishDate |
2014 |
| topic_facet |
Original contributions |
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https://nasplib.isofts.kiev.ua/handle/123456789/145386 |
| citation_txt |
Premorphological alterations in gastric mucosa in patients with gastric cancer: hypoxia level assessed by 31P NMR spectroscopy / L. Bubnovskaya, D. Osinsky, V. Trachevsky, L. Naleskina, A. Kovelskaya, L. Gumenyuk // Experimental Oncology. — 2014. — Т. 36, № 4. — С. 271-275. — Бібліогр.: 31 назв. — англ. |
| series |
Experimental Oncology |
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2025-11-24T23:52:07Z |
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2025-11-24T23:52:07Z |
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1849717767484211200 |
| fulltext |
Experimental Oncology 36, 271–275, 2014 (December) 271
PREMORPHOLOGICAL ALTERATIONS IN GASTRIC MUCOSA
IN PATIENTS WITH GASTRIC CANCER: HYPOXIA LEVEL ASSESSED
BY 31 P NMR SPECTROSCOPY
L. Bubnovskaya 1, * , D. Osinsky 2 , V. Trachevsky 3 , L. Naleskina 1 , A. Kovelskaya 1 , L. Gumenyuk 1
1 R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology,
National Academy of Sciences of Ukraine, Kyiv, Ukraine
2 City Clinical Oncological Center, Kyiv, Ukraine
3 Technical Center, NAS of Ukraine, Kyiv, Ukraine
The aim of this study was to detect the hypoxic status in adjacent histologically uninvolved gastric mucosa in gastric cancer (GC)
patients. Patients and Methods : 50 naïve patients with primary GC, and one patient with stomach ulcer (gastric mucosa was used
as control) were enrolled into the study. The tumor and mucosa samples of stomach (without muscularis and serosa layers) in patients
with GC were obtained immediately after operation. Assessment of the hypoxia level has been provided using 31 P NMR spectroscopy
in tissue perchloric acid extracts. Mucosa was examined by convenient histological method. Obtained results were analyzed statisti-
cally. Results : It was shown that gastric mucosa in 52% of patients with GC is under different levels of hypoxia, among them 23%
of mucosa is under severe hypoxia (PME/Pi < 1.0) with average mean of PME/Pi 0.89 ± 0.04. It was revealed that there are definite
associations between the hypoxia in mucosa tissue and pT as well as pN categories and G grade and stage of disease but not with
M category. Overall survival of patients with gastric mucosa characterized by severe and mild hypoxia was significantly poorer as com-
pared to that of patients with gastric mucosa with satisfactory oxygenation (p = 0.0035). Conclusion : Gastric mucosa uninvolved
in tumor process is characterized by hypoxia in 52% of GC patients; severe hypoxia of mucosa was detected in 23% of patients having
hypoxic mucosa. It was suggested that biochemical alterations in tissue surrounding tumor node may precede morphological ones.
Key Words: gastric cancer, mucosa, hypoxia.
Hypoxia is currently considered as a key factor
in tumor pathogenesis and one of the main inducer
of malignant progression. There are experimental and
clinical data that the hypoxic fraction in solid tumors
stimulates their growth and metastatic potential as well
as their sensitivity to ionizing radiation and some che-
motherapeutical agents [1–4]. It was also concluded
that hypoxia may be considered as independent factor
for prediction of disease outcome [1, 4].
It is known that tumor node is excised with the sur-
rounding tissues in accordance with the rules of the mar-
gins of resection. Resected mucosa is investigated
by histological method to control the existence of tu-
mor cells. It has to be noted that this procedure may
be performed intraoperatively to determine the status
of margin and change, if the margin will be positive,
the operation will be extended. It was shown that mi-
croscopic positive margin is an independent prognostic
factor in gastric cancer (GC) patients [5–9].
At the same time the systemic influence of tumor
on the normal tissues is known [10–15]. In this con-
text it is interesting the observations about alterations
in the noncancerous gastric mucosa in GC patients.
Sugai et al. [16] have shown that genetic alteration
already occur within the surrounding on the noncancer-
ous mucosa, in particular microsatellite alterations were
detected. It was determined the decrease of intensity
of spontaneous apoptosis and its resistance to proapop-
totic factors in extratumoral microfollicular thyroid tis-
sue with absence of macro- or microscopical features
of pathological changes in patients with thyroid carci-
noma [17]. The abnormal methylation of N33, CDH1, and
RUNX3 genes in morphologically normal mucosa in gas-
tric stump in patients operated on GC was observed [18].
The alterations in expression of Lewis antigen in adjacent
uninvolved gastric mucosal in GC patients were shown
by Kim et al. [19]. Currently the molecular assessment
of surgical-resection margins was proposed to evaluate
the margins status during GC operation to evaluate of vol-
ume operation [20]. Taking into account mentioned data
we have aimed to detect the hypoxic status in adjacent
histological uninvolved gastric mucosa in GC patients.
The numerous data about positive impact of tumor hy-
poxia on malignant progression indicate the usefulness
of providing of such study.
Meanwhile, early it was shown that oxygenation
of gastric normal tissue in patients with GC was de-
creased in comparison with that of normal gastric
tissue in patients with gastric ulcer [21]. The partial
oxygen tension in this study was measured in gastric
wall by microelectrode, but the information about
the microelectrode location, i.e., in mucosa and sub-
mucosa or in full gastric wall including muscularis and
serosa, was not presented. The histological examina-
tion of normal tissues was not performed.
It was shown that magnetic resonance spectros-
copy is a useful technique that provides insight into the
alterations of metabolic pathways in the pathological
state and information on the early biochemical changes
that are difficult to assess using as standard biochemi-
cal as well morphological methods. It is well known fact
Submitted: September 03, 2014.
*Correspondence: E-mail: bubnovskayal@ukr.net
Abbreviations used : GC — gastric cancer; PCA — perchloric acid;
PME/Pi — phosphomonoesters/inorganic phosphate.
Exp Oncol 2014
36, 4, 271–275
272 Experimental Oncology 36, 271–275, 2014 (December)
that there is a strong dependency between bioenergetic
status and oxygenation in tumor tissue since metabolic
turnover in tissue is able to adapt to the level of tissue
oxygenation, and changes in metabolic ratios may also
indicate the hypoxia level, thus permitting their applica-
tion not only for evaluation of tissue energy status but for
hypoxia as well [22]. Nuclear magnetic resonance (NMR)
spectroscopy, being a very convenient and informative
technique in vitro and in vivo investigations, has been
widely applied in oncological studies in recent decades.
The aim of the study was to characterize the gas-
tric mucosa of patients with GC as to the level of its
oxygenation.
PATIENTS AND METHODS
Patients. A total of 51 patients (30 men and
21 women) whose mucosa has been investigated were
diagnosed and operated at the City Clinical Oncological
Center (Kyiv), during period 2008–2013: 50 patients with
primary GC, and one patient with stomach ulcer (gastric
mucosa was used in this case as control). Tumors were
classified and staged according to the 2002 version
of the UICC staging system [23] (Table). All patients
were thoroughly informed about the study that was
approved by the local ethics committee.
Table. Patient and tumor characteristics
Characteristics Number of patients, n (%)
Gender
Male 30 (60.0)
Female 20 (40.0)
Age (years)
Median 65.0
Range 33–79
Tumor location
Upper third 9 (18.0)
Middle third 12 (24.0)
Lower third 27 (54.0)
Total 2 (4.0)
UICC stage
I 5 (10.0)
II 12 (24.0)
III 17 (34.0)
IV 16 (32.0)
Histological type
Adenocarcinoma 31 (62.0)
Mucinous adenocarcinoma 10 (20.0)
Signet-ring cell carcinoma 5 (10.0)
Undifferentiated carcinoma 4 (8.0)
Grade (G)
1 1 (2.0)
2 9 (18.0)
3 29 (58.0)
4 11 (22.0)
T-classification
T1 1 (2.0)
T2 6 (12.0)
T3 26 (52.0)
T4 17 (34.0)
Nodal involvement
N0 22 (44.0)
N1–2 28 (56.0)
Distant metastasis
M0 43 (86.0)
M1 7 (14.0)
The mucosa samples of stomach (without muscula-
ris and serosa layers) in patients with GC were obtained
immediately after operation. They were excised exclu-
sively at a definite distance (approximately 8–10 cm)
from the tumor node edge (beyond of obligatory opera-
tive resection) and frozen in liquid nitrogen immediately
followed by NMR spectroscopy analysis. Moreover, the
specimens of mucosa samples were fixed in 4% forma-
lin and embedded in paraffin followed by convenient
preparation and staining with hematoxylin and eosin.
NMR spectroscopy. Assessment of the hypoxia le-
vel has been provided using 31 P NMR spectroscopy in tis-
sue perchloric acid (PCA) extracts. 31 P NMR spectra were
acquired by means of a high-resolution Bruker 400 MHz
spectrometer (Widebore Ultrashield, AV-400 electronics,
Germany) using a probe of 5 mm inner diameter. 31 P NMR
spectra have been obtained in the NMR Spectroscopy
Center (G.V. Kurdyumov Institute for Metal Physics,
NAS of Ukraine). The areas of the signals on the 31 P
NMR spectra were determined by the integration mode
of the spectrometer. All details of 31 P NMR method as well
preparation of PCA tissue extracts have been presented
in our earlier publication [24].
For the assessment of the hypoxia level in tumor
as well in surrounding mucosa of patients with GC it was
used the 31 P PME/Pi metabolic ratio (phosphomonoes-
ters/inorganic phosphate) because it is very sensitive
to tissue oxygenation. As it was shown there is a highly
significant linear correlation (p < 0.001) between
the mean tissue pO 2 value and the respective PME/
Pi ratio [25]. In the Fig. 1 there is presented the 31 P
NMR spectrum of mucosa as a typical.
Fig. 1. 31 Р NMR spectrum of PCA extract of gastric uninvolved
mucosa. Copy of original spectra, patient Z.A.A.
Statistical analysis. All statistical analyses were
conducted using the NCSS 2000/PASS 2000 and Prism,
version 4.03 software packages. The survival proportion
was estimated using the Kaplan — Meier method and
differences in survival were analyzed with the log-rank
test. Prognostic values of relevant variables were ana-
lyzed by means of the Cox proportional hazards model
using Odds ratio (OR) and χ 2 test. Two-tailed p values
< 0.05 were considered statistically significant.
RESULTS AND DISCUSSION
A detailed analysis of obtained results of our recent
investigations using 31 P NMR spectroscopy [24, 26, 27]
allowed to divide gastric tumors into groups according
to the hypoxia level: severe hypoxia (PME/Pi < 1.0),
mode rate and mild hypoxia (1.0 < PME/Pi < 2.0), and
conditional “satisfactory” oxygenation (2.0 < PME/
Pi < 2.4). The median value of the PME/Pi ratio for the
GC tissue was 1.4 (range, 0.8−5.32) with average mean
Experimental Oncology 36, 271–275, 2014 (December) 273
1.49 ± 0.06, while for gastric surrounding uninvolved
mucosa the median value of PME/Pi ratio is 2.125 (range,
0.78–5.27), with average mean 2.31 ± 0.13.
Analysis of 31 P NMR spectra of PCA extracts of muco-
sa tissue showed that gastric mucosa in 52% of patients
with GC was characterized by hypoxia level below the me-
dian of the PME/Pi ratio for mucosa, i.e., they are under
different levels of hypoxia, and gastric mucosa in 48%
of patients was characterized by hypoxia level over
the median, i.e., it is under “satisfactory” oxygenation.
In order to reveal distribution of mucosa tissue
as to the level of hypoxia in the patients with GC it has
been used the scheme of division as to the level of hypox-
ia for tumor tissue. It was obtained that 12% of mucosa
are under severe hypoxia (PME/Pi < 1.0; with average
mean of PME/Pi 0.89 ± 0.04, 34% of mucosa are under
different levels of moderate hypoxia (1.0 < PME/P < 2.0;
with average mean of PME/Pi 1.66 ± 0.06); and the rest
ones have satisfactory oxygenation (PME/Pi > 2.0; with
average mean of PME/Pi 2.93 ± 0.14).
As an example for the comparison we had the sam-
ple of gastric mucosa of patient who has been operated
on gastric ulcer. It was characterized by very high level
of oxygenation, i.e., PME/Pi 3.17.
In the group of patients with GC (n = 13) with the
tumor characterized by severe hypoxia (PME/Pi < 1.0)
mucosa has been found under the same condition
in 38.5% of cases, under moderate hypoxia — in 38.5%
also and satisfactory oxygenated mucosa — in 23.1%.
In the group of patients with GC (n = 23) with tumor
under different levels of hypoxia (1.0 < PME/P < 2.0) —
only 4.3% of mucosa tissue was under severe hypoxia,
52.2% — under moderate hypoxia and 43.5% — sa-
tisfactory oxygenated. The complete coincidence
as to the level of oxygenation there was in the group
of patients with tumors that are satisfactory oxygenated
(PME/P > 2.0).
The hypoxia level in GC was correlated neither
with pT or M categories (TNM system) nor with stages
of disease. At the same time, a very important inter-
relationship between high levels of hypoxia in primary
tumors an appearance of metastases in lymph nodes
of patients with GC has been established [28]. Taking
into account the above mentioned it has been provided
the analysis whether there is the association between
the level of hypoxia in mucosa with clinico-pathological
characteristics of patients with GC. It was also revealed
that there are definite associations between the hypo xia
in mucosa tissue and pT as well as pN categories and
G grade and stage of disease but not with M category.
It was shown that patients with pТ 4 category are
4.0 times more likely to have surrounding mucosa
under hypoxic condition (PME/Pi < 2.125) than pa-
tients with pТ 1–3 categories (OR = 3.69, χ 2 = 4.37, 95%
CI 1.0522–12.957, p = 0.0414); patients with node-posi-
tive tumors (pN 1–2 ) 5.0 times more (OR = 5.63, χ 2 = 8.11,
95% CI 1.6478–19.2329, p = 0.0058) than patients
with node-negative tumors (pN 0 ) as well patients with
G 3–4 in comparison with patients with G 1–2 categories
(OR = 5.412, χ 2 = 4.51, 95% CI 1.0172–28.792, p = 0.0477).
It was not obtained any associations between
the hypoxia level in adjacent “normal” mucosa
of patients with GC and M category. At the same time
it was observed that GC patients with III/IV stage have
the more probability for surrounding mucosa to be hy-
poxic than patients with I/II stage (OR = 5.68, χ 2 = 7.215,
95% CI 1.5098–21.4245, p = 0.0102).
Overall, 21 patients with GC (42%) died during
follow-up: among them 70% who had hypoxic mu-
cosa (PME/P < 2.125) and 33.3% — when mucosa
was sa tisfactory oxygenated (PME/P > 2.125). Ana-
lyzing the survival of these GC patients as to the level
of hypoxia in surrounding mucosa it was obtained that
mean survival time in the group of patients with hy-
poxic mucosa (PME/P < 2.125) was significantly
shorter compared to that in the group of patients with
satisfactory oxyge nated mucosa: 17.2 ± 2.2 months and
32.4 ± 3.2 months, respectively. Survival time of patients
with GC in accordance with the type of therapy has been
detected: operation alone and operation with adjuvant
chemotherapy (standard regimes). The following re-
sults were obtained: survival time of patients who were
operated only was 15.5 ± 2.05 months when uninvolved
mucosa was hypoxic (PME/Pi median < 2.125) and
35.4 ± 4.2 when uninvolved mucosa was satisfactory
oxygenated (PME/Pi > 2.125); survival time of patients
who have been treated with adjuvant chemotherapy
was 14.6 ± 3.7 months when uninvolved mucosa was
hypoxic and 23.4 ± 1.4 when mucosa was satisfactory
oxygenated. It has to be noted that the same associa-
tions between survival time of patients treated by dif-
ferent methods and hypoxia level in GC were found.
Analysis of survival of all patients with GC as a func-
tion of the PME/Pi ratio (i.e., in dependence upon
the level of hypoxia in GC mucosa) has revealed that
overall survival of patients with gastric mucosa cha-
racterized by PME/Pi < 2.125 (severe and mild hy-
poxia) was significantly poorer as compared to patients
with gastric mucosa characterized by satisfactory
oxygenation (PME/Pi > 2.125) ( p = 0.0035, Fig. 2).
0
0
20
40
60
80
100
100 200 300 400 500
Weeks
Su
rv
iva
l,
%
Fig. 2. Kaplan — Meier overall survival curves for GC patients
as a function of PME/Pi ratio in adjacent uninvolved gastric mu-
cosa (PME/Pi ratio over median, thin line; PME/Pi below median,
bold line; median is 2.125; p < 0.0035)
Histological examination has not found any signs
of neoplastic transformation in the surrounding gastric
mucosa located at a distance of 8–10 cm from the tumor
edge (Fig. 3, 4).
274 Experimental Oncology 36, 271–275, 2014 (December)
Fig. 3. Gastric mucosa surrounding gastric carcinoma. Gastric
mucosa shows no signs of pathological alterations (hematoxylin
and eosin; × 100)
Fig. 4. Gastric mucosa surrounding gastric carcinoma. Surface
and pit epithelium, and epithelium lining the glands show no signs
of malignant transformation (hematoxylin and eosin; × 400)
At the same time the pathological alterations in the
gastric mucosa surrounding tumors were observed.
In some cases, mucosa demonstrated the evidence
of atrophic gastritis manifested by the smoothness
of folds, changes of the depth of pits and height
of surface epithelium, reduction of secretory activity
of epithelium (Fig. 5).
Moreover, the signs of the erosive gastritis were
also observed (Fig. 6). It is notable that deeper located
glands were covered by secretory cylindrical epithe-
lium without signs of atypia. It has to be mentioned
that Arista-Nasr et al. [29] have also shown that gastric
carcinomas are frequently accompanied by atrophy,
intestinal metaplasia and dysplasia of the surrounding
non-neoplastic gastric mucosa.
Thus, taking into account the results of histologi-
cal examination it could be supposed that metabolic
changes in gastric mucosa surrounding gastric carci-
noma, in particular increase of hypoxia level, appear
before the morphological alterations in mucosa which
can be assessed as neoplastic transformation. Ob-
served metabolic rearrangement in gastric mucosa may
be influenced by tumor which affects normal tissues
confirming the existence of active tumor-host interac-
tion. It has to be noted that the similar phenomenon,
in particular the alterations of cytogenetic indices in sur-
rounding normal tissues by the development of GC,
endometrial carcinoma, and tumor from the pigment
tissue were shown by Ganina et al. [30–32].
Fig. 5. Atrophy of the gastric mucosa surrounding gastric
carcinoma. The decrease of the number of glands and damage
of their architectonics and secretory activity are shown (hema-
toxylin and eosin; × 100)
Fig. 6. Erosive gastritis. The disturbance of integrity of surface
epithelium of gastric mucosa, extensive inflammatory infiltrate
were observed. The glands located deeper are not altered, co-
vered with cylindric epithelium with the signs of secretory activity
(hematoxylin and eosin; × 400)
In conclusion, it may be summarized that gastric
mucosa uninvolved in tumor process is characterized
by hypoxia in 52% of GC patients. Histological examina-
tion of mucosa specimens has not found cancer cells
or signs of malignization. It has to be noted that severe
hypoxia of mucosa was detected in 23% of patients with
hypoxic mucosa. It was also found that severe hypoxia
in tumor was accompanied with severe hypoxic mucosa
in 38.5% of cases. Taking into account obtained data
and some data of other authors it may be suggested that
biochemical alterations in tissue surrounding tumor node
and uninvolved in malignant process may precede mor-
phological ones. This phenomenon needs to be studied
more widely, including decoding its mechanisms.
ACKNOWLEDGEMENTS
This research was supported by the National Aca-
demy of Sciences of Ukraine (Grants no. 2.2.5.309 and
no. 2.2.5.365).
Experimental Oncology 36, 271–275, 2014 (December) 275
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