Histopathology 1990, 17, 537-541
Helicobacter pylori and gastric carcinoma R.J.L.F.LOFFELD, I.WILLEMS, J.A.FLENDRIG & J.W.AKENDS* Departments of Internal Medicine and *Pathology, University Hospital Maastricht, The Netherlands Date of submission 2 7 February 1990 Accepted for publication 3 0 May 1990
LOFFELD
R.J.L.F.,
WILLEMS I . , F L E N D R I G
J.A. &
ARENDS J.W.
(1990) Histopathology 17, 537-541
Helicobacter pylori and gastric carcinoma A retrospective study was performed on gastric carcinomas to establish the prevalence of Helicobucter pylori infection in gastric epithelium adjacent to the tumour. A total of 1 0 5 carcinomas were studied. The overall prevalence of Helicobacter pylori infection was 59%. The prevalence in different age cohorts from patients with gastric carcinoma was compared with that in patients suffering from non-ulcer dyspepsia and, based on serological testing, with that in healthy blood donors. The presence of Helicobacter pylori in cancer patients aged
41-50 and 5 1-60 was significantly higher than in blood donors. No difference was seen in comparison with nonulcer dyspepsia patients. The presence of Helicobacter pylori showed an inverse correlation with the extent of intestinal metaplasia. The intestinal type of carcinoma was associated with a higher bacterial load than the diffuse type. These data suggest that the presence of Helicobacter pylori in gastric mucosa could play a role in the pathogenesis of gastric carcinoma, especially in the younger age group.
Keywords: Helicobacter pylori, gastritis, gastric carcinoma, intestinal metaplasia, intestinal type gastric carcinoma
Introduction Helicobacter pylori (formerly Carripylobucter pylori) is the major cause of type B, antral, gastritisl-j, characterized by an acute and chronic inflammatory infiltrate in the superficial portion of the lamina propria and around groups of gastric glands. Antral gastritis predisposes to the development of chronic atrophic gastritis and peptic ulcer disease4. It is questionable, however, whether the condition also predisposes to the development of gastric carcinoma. Krienitz' postulated that the spiral organisms could be of relevance with regard to the aetiology of the tumour. Glands in which Helicobacter pylori are present display increased proliferative activity. It is conceivable, therefore, that the micro-organism could act as an irritant of the gastric mucosa and induce excessive cell replication, thus acting as a cancer promoterh. In this context it is of interest to study the presence of Helicobacter pylori in gastric carcinoma. In the literature, conflicting data have been presented on the occurrence of Hrlicobacter pylori infection in cases of gastric carcinoma7-'. In this report we describe a Address for correspondence: Dr R.J.L.F.Loffeld,Department of Internal Medicine. University Hospital Maastricht, PO Box 191 8. 6201 BX Maastricht. The Netherlands.
retrospective study on biopsies and resection specimens to establish the prevalence of Helicobacter pylori in different types of gastric carcinoma. We compare the observed prevalence in different age groups of gastric cancer patients with serologically determined data on the presence of Helicobacter pylori in blood donors and with histological and microbiological data on its presence in non-ulcer dyspepsia patients.
Materials and methods For the purpose of the study, all gastric carcinomas diagnosed in the period 1980 to 1984 in the University Hospital, Maastricht were retrieved from our files. The material consisted of 105 carcinomas from 6 4 men and 41 women (mean age 67.2 years, range 41-97). The presence of Helicobucter pylori was studied in biopsy specimens and/or specimens from surgically removed tumours. All material was recut and sections were stained with a modification of the Giemsa method for detection of Helicobucter pylori, as previously described'". The presence of Helicobucter pylori was scored semiquantitatively: grade 0-no bacteria; grade 1sporadic bacteria: grade 2-many bacteria; and grade 3-many bacteria seen and also lying in clusters. 537
538
R.].L.F.Loffeld et al.
Haematoxylin and eosin stained sections of the tumours were re-evaluated, with the tumour differentiation scored as poor or high and the type (intestinal or diffuse) noted. The extent of intestinal metaplasia was scored semiquantitatively: grade &none; grade 1focal; grade 2-less than half of the epithelium present in the section affected: and grade 3-more than half of the epithelium affected. The presence of Helicobacter pylori in different age cohorts of patients with gastric carcinoma was compared with seropositive blood donors and Helicobacter pylori positive non-ulcer dyspepsia patients. Sera from 4 1 5 blood donors was tested for IgG antibodies against Helicobucter pylori, as described elsewhere' . The criterion for seropositivity was a cut-off value shown to have a high predictive value for Helicobucter pylori gastritis12. A total of 2 0 0 patients suffering from non-ulcer dyspepsia were studied histologically and microbiologically for the presence of Helicobacter pylori. Some details of this group have already been published"'. Statistical analysis was done with the chi-square test.
'
Results Forty-five carcinomas were represented in biopsy specimens as well as in resection specimens, 2 3 were represented only as resection specimens and in the remaining 3 7 only biopsy specimens were available. Fourteen carcinomas had to be excluded from evaluation due to absence of normal epithelium in the available sections. These specimens only showed
tumour or necrotic tissue. The majority of these cases were carcinomas of the diffuse type. Tissue from the remaining 9 1 carcinomas was examined. Helicobacter pylori was demonstrated in the mucosa adjacent to the tumour in 54 carcinomas (59%).There was no difference between biopsy specimens and resection specimens; 34 (57%)of the former and 28 (46%)of the latter revealed Helicobacter pylori. If bacterial load was taken into account no difference was seen between biopsy specimens and resection specimens, as shown in Table 1, although there was a tendency for a slightly higher bacterial load in the biopsy specimens. Of the 4 5 carcinomas from which biopsy and resection material was available, two resection specimens and 1 3 biopsy specimens had to be excluded because the sections did not reveal normal gastric epithelium. Of the 3 0 which could be evaluated, 16resection specimens and 1 5 biopsies were negative for Helicobacter pylori; 10 and 11, respectively, scored grade 1, and four in each group scored grades 2 and 3. Comparison of the resection and biopsy data showed no statistically significant difference. The majority (78%) of the highly differentiated tumours revealed Helicobacter pylori. while this figure was 45% in the carcinomas showing poor differentiation (Table 1).No difference was seen in the prevalence of Helicobacter pylori in diffuse, as compared with intestinal type carcinoma (Table 1).However, thert: was a tendency towards a higher bacterial load in cases of the intestinal type. The diffuse type was negative for Helicobacterpylori in 54% of cases and for the intestinal type in 40%. Helicobacter pylori was present in large numbers in
Helicobacter score ("/o of total) 0
1
213
Total
Nature of specimen Kesection Biopsy
33 (54) 26 (43)
1 7 (28) 17 (28.5)
11 (18) 1 7 (28.5)
61 60
Turnour differentiation Poorly differentiated Highly differentiated
37 (45) 1(11)
21 (24) 5 (56)
2 4 (31) 3 (33)
82 9
Turnour type Diffuse Intestinal
6 (54) 32 (40)
3 (27) 23 (29)
2 (19) 2 5 (31)
80
Intestinal rnetaplasia Grade O/ 1 Grade 213
19 (35)* 2 0 (56)
1 5 (27)
21 (38) 5 (14)
55 36
11 (30)
*Difference between grade 011 and grade 213 statistically significant, P
Helicobacter pylori and gastric carcinoma R.J.L.F.LOFFELD, I.WILLEMS, J.A.FLENDRIG & J.W.AKENDS* Departments of Internal Medicine and *Pathology, University Hospital Maastricht, The Netherlands Date of submission 2 7 February 1990 Accepted for publication 3 0 May 1990
LOFFELD
R.J.L.F.,
WILLEMS I . , F L E N D R I G
J.A. &
ARENDS J.W.
(1990) Histopathology 17, 537-541
Helicobacter pylori and gastric carcinoma A retrospective study was performed on gastric carcinomas to establish the prevalence of Helicobucter pylori infection in gastric epithelium adjacent to the tumour. A total of 1 0 5 carcinomas were studied. The overall prevalence of Helicobacter pylori infection was 59%. The prevalence in different age cohorts from patients with gastric carcinoma was compared with that in patients suffering from non-ulcer dyspepsia and, based on serological testing, with that in healthy blood donors. The presence of Helicobacter pylori in cancer patients aged
41-50 and 5 1-60 was significantly higher than in blood donors. No difference was seen in comparison with nonulcer dyspepsia patients. The presence of Helicobacter pylori showed an inverse correlation with the extent of intestinal metaplasia. The intestinal type of carcinoma was associated with a higher bacterial load than the diffuse type. These data suggest that the presence of Helicobacter pylori in gastric mucosa could play a role in the pathogenesis of gastric carcinoma, especially in the younger age group.
Keywords: Helicobacter pylori, gastritis, gastric carcinoma, intestinal metaplasia, intestinal type gastric carcinoma
Introduction Helicobacter pylori (formerly Carripylobucter pylori) is the major cause of type B, antral, gastritisl-j, characterized by an acute and chronic inflammatory infiltrate in the superficial portion of the lamina propria and around groups of gastric glands. Antral gastritis predisposes to the development of chronic atrophic gastritis and peptic ulcer disease4. It is questionable, however, whether the condition also predisposes to the development of gastric carcinoma. Krienitz' postulated that the spiral organisms could be of relevance with regard to the aetiology of the tumour. Glands in which Helicobacter pylori are present display increased proliferative activity. It is conceivable, therefore, that the micro-organism could act as an irritant of the gastric mucosa and induce excessive cell replication, thus acting as a cancer promoterh. In this context it is of interest to study the presence of Helicobacter pylori in gastric carcinoma. In the literature, conflicting data have been presented on the occurrence of Hrlicobacter pylori infection in cases of gastric carcinoma7-'. In this report we describe a Address for correspondence: Dr R.J.L.F.Loffeld,Department of Internal Medicine. University Hospital Maastricht, PO Box 191 8. 6201 BX Maastricht. The Netherlands.
retrospective study on biopsies and resection specimens to establish the prevalence of Helicobacter pylori in different types of gastric carcinoma. We compare the observed prevalence in different age groups of gastric cancer patients with serologically determined data on the presence of Helicobacter pylori in blood donors and with histological and microbiological data on its presence in non-ulcer dyspepsia patients.
Materials and methods For the purpose of the study, all gastric carcinomas diagnosed in the period 1980 to 1984 in the University Hospital, Maastricht were retrieved from our files. The material consisted of 105 carcinomas from 6 4 men and 41 women (mean age 67.2 years, range 41-97). The presence of Helicobucter pylori was studied in biopsy specimens and/or specimens from surgically removed tumours. All material was recut and sections were stained with a modification of the Giemsa method for detection of Helicobucter pylori, as previously described'". The presence of Helicobucter pylori was scored semiquantitatively: grade 0-no bacteria; grade 1sporadic bacteria: grade 2-many bacteria; and grade 3-many bacteria seen and also lying in clusters. 537
538
R.].L.F.Loffeld et al.
Haematoxylin and eosin stained sections of the tumours were re-evaluated, with the tumour differentiation scored as poor or high and the type (intestinal or diffuse) noted. The extent of intestinal metaplasia was scored semiquantitatively: grade &none; grade 1focal; grade 2-less than half of the epithelium present in the section affected: and grade 3-more than half of the epithelium affected. The presence of Helicobacter pylori in different age cohorts of patients with gastric carcinoma was compared with seropositive blood donors and Helicobacter pylori positive non-ulcer dyspepsia patients. Sera from 4 1 5 blood donors was tested for IgG antibodies against Helicobucter pylori, as described elsewhere' . The criterion for seropositivity was a cut-off value shown to have a high predictive value for Helicobucter pylori gastritis12. A total of 2 0 0 patients suffering from non-ulcer dyspepsia were studied histologically and microbiologically for the presence of Helicobacter pylori. Some details of this group have already been published"'. Statistical analysis was done with the chi-square test.
'
Results Forty-five carcinomas were represented in biopsy specimens as well as in resection specimens, 2 3 were represented only as resection specimens and in the remaining 3 7 only biopsy specimens were available. Fourteen carcinomas had to be excluded from evaluation due to absence of normal epithelium in the available sections. These specimens only showed
tumour or necrotic tissue. The majority of these cases were carcinomas of the diffuse type. Tissue from the remaining 9 1 carcinomas was examined. Helicobacter pylori was demonstrated in the mucosa adjacent to the tumour in 54 carcinomas (59%).There was no difference between biopsy specimens and resection specimens; 34 (57%)of the former and 28 (46%)of the latter revealed Helicobacter pylori. If bacterial load was taken into account no difference was seen between biopsy specimens and resection specimens, as shown in Table 1, although there was a tendency for a slightly higher bacterial load in the biopsy specimens. Of the 4 5 carcinomas from which biopsy and resection material was available, two resection specimens and 1 3 biopsy specimens had to be excluded because the sections did not reveal normal gastric epithelium. Of the 3 0 which could be evaluated, 16resection specimens and 1 5 biopsies were negative for Helicobacter pylori; 10 and 11, respectively, scored grade 1, and four in each group scored grades 2 and 3. Comparison of the resection and biopsy data showed no statistically significant difference. The majority (78%) of the highly differentiated tumours revealed Helicobacter pylori. while this figure was 45% in the carcinomas showing poor differentiation (Table 1).No difference was seen in the prevalence of Helicobacter pylori in diffuse, as compared with intestinal type carcinoma (Table 1).However, thert: was a tendency towards a higher bacterial load in cases of the intestinal type. The diffuse type was negative for Helicobacterpylori in 54% of cases and for the intestinal type in 40%. Helicobacter pylori was present in large numbers in
Helicobacter score ("/o of total) 0
1
213
Total
Nature of specimen Kesection Biopsy
33 (54) 26 (43)
1 7 (28) 17 (28.5)
11 (18) 1 7 (28.5)
61 60
Turnour differentiation Poorly differentiated Highly differentiated
37 (45) 1(11)
21 (24) 5 (56)
2 4 (31) 3 (33)
82 9
Turnour type Diffuse Intestinal
6 (54) 32 (40)
3 (27) 23 (29)
2 (19) 2 5 (31)
80
Intestinal rnetaplasia Grade O/ 1 Grade 213
19 (35)* 2 0 (56)
1 5 (27)
21 (38) 5 (14)
55 36
11 (30)
*Difference between grade 011 and grade 213 statistically significant, P
