Cell Biochem Biophys DOI 10.1007/s12013-014-0052-z
ORIGINAL PAPER
An Association Study of Histological Types of Gastric Carcinoma with Helicobacter pylori Infection Xia Wang • Muxin Wei • Zhiguang Sun
Ó Springer Science+Business Media New York 2014
Abstract The aim of this study was to study the relation between histopathological classification of gastric carcinoma and Helicobacter pylori (H. pylori) infection. 200 patients with confirmed gastric carcinoma between January 2010 and January 2012 from our hospital were included. All these patients went through endoscopy and histological examinations for gastric carcinoma and immunological test for H. pylori infection. Patients were grouped according to the histological classification, and the infection rates of H. pylori in different groups were compared. Types of gastric cancer that was closely related to H. pylori infection were identified. Infection rate in patients with the intestinal type of gastric cancer was significantly higher compared to those with the diffuse type. For tubular type of carcinoma, the well to medium-differentiated group had a significantly higher infection rate than the poorly differentiated group. Helicobacter pylori infection and histological types were relevant. The effect of H. pylori infection on the intestinal type was more significant than that on the diffuse type. The infection rate of well-differentiated group was higher than that of the poorly differentiated group, which suggested an association between H. pylori infection and the degree of differentiation of tubular cancerous tissue. X. Wang Nanjing University of Traditional Chinese Medicine, Nanjing, China X. Wang M. Wei Department of Chinese Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China Z. Sun (&) Jiangsu Provincial Hospital of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing 210029, China e-mail: [email protected]
Keywords Gastric cancer H. pylori Histological classification
Introduction Although there has been a progressive decline in the incidence of gastric carcinoma all over the world, it remains the fourth most common malignancy worldwide and the second most prevalent in China [1–3]. Among 934,000 new cases each year, China accounts for 42 %, with morbidity and mortality rate twofold more than that globally [4]. The most direct etiological association of gastric carcinoma has been established with Helicobacter pylori (H. pylori). H. pylori were declared a type-1 carcinogen by the International Agency for Research on Cancer (IARC) [5]. Several epidemiologic studies provide evidences for the role of H. pylori in the pathogenesis of gastric carcinoma [6–8]. A 10-year follow-up study with a total of 1,228 gastric cancer cases showed a sixfold increase in relative risk of gastric carcinoma [8]. Furthermore, H. pylori eradication treatment was associated with reduction in the risk of gastric carcinoma [7]. In the animal study with Mongolian gerbils, it was demonstrated that long-term infection with H. pylori induces adenocarcinoma in Mongolian gerbils, and all induced tumors consisted of welldifferentiated intestinal-type epithelium [9]. Human studies on the association between different histological types of gastric carcinoma with H. pylori infection have been conflicting [10–13]. In this study, we aimed to investigate the relationship between gastric carcinoma and H. pylori infection based on histological types, and to further study the association between H. pylori infection with gastric carcinoma of various degree of differentiations.
123
Cell Biochem Biophys
Methods
Table 1 Histological classification by Lauren’s criteria and WHO standard
Patients and Grouping
Histological type
Two hundred patients with proven gastric carcinoma diagnosed at our hospital between January 2011 and June 2013 were included in this study. All patients underwent an upper gastrointestinal endoscopy, with biopsy specimens obtained from the tumor. Gastric carcinoma was diagnosed, and the degree of differentiation was assessed by an experienced pathologist.
Histological types of gastric carcinoma by Lauren’s criteria
Histological Assessment and Grouping Gastric biopsy specimens were obtained endoscopically from the tumor site under direct vision in all subjects. Biopsy specimens were fixed overnight in buffer formalin, embedded in paraffin, cut to 4-lm thickness, and then stained with hematoxylin and eosin for observation. The gastric carcinomas were classified histologically on the basis of two standards: the Lauren’s criteria [14] and WHO standard [15]. In accordance with the Lauren criteria, gastric carcinoma was categorized into intestinal, diffuse, and unclassified types. Under the WHO classification, gastric carcinoma was classified into tubular, mucinous, papillary, signet ring cell, adenosquamous, carcinoid carcinoma, and the rest of other types. Since tubular carcinoma accounts for most of the gastric carcinoma, it was further divided into subtypes according to the degree of differentiation. Detection of H. pylori Infection Blood sample was collected from all patients, and H. pylori infection was examined by detecting IgG antibody to this organism by enzyme-linked immunosorbent assay (ELISA). Statistical Analysis Statistical analysis was performed on SPSS17.0. v2 test was carried out to test the correlation between the histological typing and the H. pylori infection rate.
n (%)
Intestinal
39 (19.5)
Diffuse Indeterminate
125 (62.5) 36 (18)
Histological types of gastric carcinoma by WHO standard Tubular Well differentiated
147 (73.5 %) 3
Well to medium differentiated
14
Medium differentiated
26
Medium to poor differentiated
38
Poor differentiated
66
Mucinous
42 (21 %)
Papillary
2 (1 %)
Signet ring cell Adenosquamous
4 (2 %) 2 (1 %)
Carcinoid
1 (0.5 %)
Others
2 (0.5 %)
According to Lauren’s criteria, 39 cases (19.5 %) of gastric cancer were classified as intestinal type and 125 (62.5 %) as diffuse type. The remaining 36 (18 %) were unclassified. Under the WHO classification, 147 (73.5 % of 200 cases) cases were of tubular carcinoma, 42 cases (21 %) were of mucinous carcinoma, 2 cases (1 %) were of papillary carcinoma, 4 cases (2 %) were of signet ring cell carcinoma, 2 cases (1 %) were of adenosquamous carcinoma, 1 case (0.5 %) were of carcinoid, and the rest (1 %) were of other types. Among 147 case of tubular carcinoma, it was further divided into subtypes: 3 cases were of well differentiated, 14 cases were of well-medium differentiated, 26 cases were of medium differentiated, 38 cases were of medium-poorly differentiated, and 66 cases of poorly differentiated. In total, 92 out of 200 (46 %) patients were tested positive with H. pylori based on ELISA. H. pylori Infection Rate Compared Across the Subtypes Classified by the Lauren’s Criteria
Results Patient Characteristics The mean age of the 200 patients with gastric carcinoma was 59.9 years old, with the range of 30–79 years old. There were 70 males (35 %) and 130 females (65 %). Patients were categorized into groups based on Lauren’s classification and WHO classification as shown in Table 1.
123
The relationship between H. pylori infection and the histologic type of gastric cancer based on Lauren’s criteria is shown in Table 2. Infection rate was significantly higher in the intestinal type of gastric cancer compared with the diffuse type (P \ 0.05). No significant difference was found in the infection rates between diffuse and indeterminate types and between intestinal and indeterminate types.
Cell Biochem Biophys Table 2 H. pylori infection rate of subtypes classified by Lauren’s criteria
Table 4 H. pylori infection rate of different subtypes of tubular carcinoma based on degree of differentiation
Lauren’s classification
Degree of differentiation
H. pylori negative
H. pylori positive
Total number of cases
Infection rate
Well/WellMedium/ Medium
17
26
43
60.5 %
H. pylori negative
H. pylori positive
Total number of cases
Infection rate
Intestinal type
16
23
39
58.9 %*
Diffuse type
74
51
125
40.8 %*
Indeterminate type
18
18
36
50 %
v2
8.40*
P value
\0.05*
Medium-poor
18
20
38
52.6 %
Poor
44
22
66
33.3 %
v2 P value
H. pylori Infection Rate Compared Across the Subtypes Classified by WHO Standard The relationship between H. pylori infection and the histological types of gastric cancer based on WHO standard is shown in Table 3. Tubular and mucinous cancer account for most of the cases in the cohort (94.5 %), which made it meaningless to compare these two subtypes to the rest of subtypes. Thus, only tubular and mucinous types were compared, and no significant difference was found in the infection rate between these two. H. pylori Infection Rate Compared Across the Subtypes of Tubular Type Based on Degree of Differentiation The infection rates among tubular types of different differentiations were significantly different (P \ 0.05), as shown in Table 4. The infection rates increased proportionally with the degree of differentiation, with the lowest infection rate at the poorly differentiated and the highest in the well differentiated. Exemplary histological images of tubular gastric carcinoma with different degrees of differentiation are shown in Fig. 1.
Table 3 H. pylori infection rate of subtypes classified by WHO standard WHO classified subtype
H. pylori negative
H. pylori positive
Total number of cases
Infection rate
Tubular
79
68
147
46.2 %*
Mucinous
21
21
42
50 %*
Papillary
1
1
2
50 %
Signet ring cell
3
1
4
25 %
Adenosquamous
2
0
2
0
Carcinoid
1
0
1
0
Other types
2
0
2
0
v2 P value
0.13* [0.05*
12.41 \0.05
Discussion Two classification systems are commonly used for histological categorization of gastric carcinoma. Lauren first categorized gastric carcinoma into two major subtypes: intestinal and diffuse subtypes based on microscopic appearance and growth patterns [14]. The intestinal type resembles normal intestinal mucosa, while diffuse type consists of discohesive poorly differentiated cells without recognizable gland formation. The 2010 WHO classification recognizes four major histologic patterns of gastric cancers: tubular, papillary, mucinous, and poorly cohesive (including signet ring cell carcinoma), plus uncommon histologic variants (15). The classification is based on the predominant histologic pattern of the carcinoma. In our study, 200 patients were grouped under both standards; the relationship between different histological types of gastric carcinoma and H. pylori infection was investigated. Helicobacter pylori infection is implicated in the pathophysiology of gastric carcinoma [6, 10, 11]. Now, it is generally believed that H. pylori induce a chronic inflammation in stomach, which ultimately progresses into atrophic gastritis. Atrophic gastritis and intestinal metaplasia are considered to be the precursor lesions of the intestinal type of gastric cancer [9]. Earlier studies also indicated that there are important clinical, histological, and demographic differences between intestinal and diffusetype gastric cancer. It is generally accepted that intestinaltype gastric carcinoma is related to atrophic gastritis [13, 16]. Our data show that infection rate was significantly higher in the intestinal type of gastric cancer compared with the diffuse type (P \ 0.05), which is consistent with the observations from others [11, 12]. We did not find any correlation of H. pylori infection with histological types of gastric carcinoma based on the WHO classification. However, our data suggested that there is a relationship between H. pylori infection and gastric carcinoma differentiation, with the lowest infection rate at the poorly differentiated and the highest in the well
123
Cell Biochem Biophys
Fig. 1 Histological image of tubular adenocarcinoma with different degrees of differentiation. a well differentiated; b medium differentiated; c poorly differentiated tubular adenocarcinoma
differentiated in the tubular type of gastric carcinoma. This result is reasonable considering the differentiated and undifferentiated types in our classification corresponded well with the intestinal and diffuse types of Lauren’s criteria. Helicobacter pylori positive rate of 46 % in our study is relatively low compared with other studies; however, geographic difference should be taken into consideration when making such comparison. Data obtained from more than 50 counties of rural China revealed that the proportion of the population positive for H. pylori antibodies varied from 26 to 96 % [17]. Studies that have examined the relationship between gastric cancer and H. pylori infection also showed a great variability [18]. Karnes et al. reported that prolonged atrophy may cause the spontaneous disappearance of H. pylori from the gastric mucosa and a fall in the antibody titer [19], which may also account for the variability. In summary, H. pylori infection and histological types were related. The effect of H. pylori infection on the intestinal type was more significant than that on the diffuse type. The infection rate of well-differentiated group was higher than that of the poorly differentiated group, which suggested an association between H. pylori infection and the degree of differentiation of gastric carcinoma. Acknowledgments This study was funded by Provincial Bureau of Traditional Chinese Medicine of Jiangsu, fund project #LZ13247.
References 1. Cancer (Fact Sheet No. 297) (February 2014). World Health Organization. Retrieved May 11, 2009. 2. Jemal, A., Bray, F., Center, M. M., Ferlay, J., Ward, E., & Forman, D. (2011). Global cancer statistics. CA: A Cancer Journal for Clinicians, 61(2), 69–90. 3. DeVita, V. T., Lawrence, T. S., Rosenberg, S. A., DePinho, R. A., & Weinberg, A. (2011). Principles and practice of oncology (9th ed., North American Edition ed.). Philadelphia, PA: Lippincott Williams & Wilkins.
123
4. Yang, L. (2006). Incidence and mortality of gastric cancer in China. World Journal of Gastroenterology, 12(1), 17–20. 5. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. (2010). IARC monographs on the evaluation of carcinogenic risks to humans. Ingested nitrate and nitrite, and cyanobacterial peptide toxins. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, 94, 1. 6. Parsonnet, J., Friedman, G. D., Vandersteen, D. P., Chang, Y., Vogelman, J. H., Orentreich, N., et al. (1991). Helicobacter pylori infection and the risk of gastric carcinoma. New England Journal of Medicine, 325, 1127–1131. 7. Fuccio, L., Zagari, R. M., Eusebi, L. H., Laterza, L., Cennamo, V., Ceroni, L., et al. (2009). Meta-analysis: Can Helicobacter pylori eradication treatment reduce the risk for gastric cancer? Annals of Internal Medicine, 151(2), 121–128. 8. Webb, P. M. (2001). Gastric cancer and Helicobacter pylori: A combined analysis of 12 case control studies nested within prospective cohorts. Gut, 49(3), 347–353. 9. Watanabe, T., Tada, M., Nagai, H., Sasaki, S., & Nakao, M. (1998). Helicobacter pylori infection induces gastric cancer in Mongolian gerbils. Gastroenterology, 115(3), 642–648. 10. Loffeld, R. J. L. F., Willems, I., Flendrig, J. A., & Arends, J. W. (1990). Helicobacter pylori and gastric carcinoma. Histopathology, 17, 537–541. 11. Parsonnet, J., Vandersteen, D., Goates, J., Sibley, R. K., Pritikin, J., & Chang, Y. (1991). Helicobacter pylori infection in intestinal- and diffuse-type gastric adenocarcinomas. Journal of the National Cancer Institute, 83, 640–643. 12. Martı´n-de-Argila, C., Boixeda, D., Redondo, C., Alvarez, I., Gisbert, J. P., Garcı´a Plaza, A., et al. (1997). Relation between histologic subtypes and location of gastric cancer and Helicobacter pylori. Scandinavian Journal of Gastroenterology, 32(4), 303–307. 13. Komoto, K., Haruma, K., Kamada, T., Tanaka, S., et al. (1998). Helicobacter pylori infection and gastric neoplasia: Correlations with histological gastritis and tumor histology. American Journal of Gastroenterology, 93(8), 1271–1276. 14. Lauren, P. (1965). The two histological main types of gastric carcinoma, diffuse and so-called intestinal-type carcinoma: An attempt at a histo-clinical classification. Acta Patholog Microbiology Scand, 64, 31–49. 15. Lauwers, G. Y., Carneiro, F., & Graham, D. Y. (2010). Gastric carcinoma. In F. T. Bowman, F. Carneiro, & R. H. Hruban (Eds.), Classification of tumours of the digestive system. Lyon: IARC.
Cell Biochem Biophys 16. Talley, N. J., Zinsmeister, A. R., Weaver, A., et al. (1991). Gastric carcinoma and Helicobacter pylori infection. Journal of the National Cancer Institute, 83, 1734–1739. 17. Forman D, Sitas F, Newell DG, Stacey, AR Boreham J, Peto R, Campbell TC, Li J, Chen J. Geographic association of Helicobacter pylori antibody prevalence and gastric cancer mortality in rural China. International Journal of Cancer. 46(4), 608 ISSN 0020-7136, 10/1990.
18. Forman, D. (1995). The Prevalence of Helicobacter Pylori infection in gastric cancer. Alimentary Pharmacology & Therapeutics, 9(Suppl 2), 714. 19. Karnes, W. E., Samloff, I. M., Jr, Siurala, M., et al. (1991). Positive serum antibody and negative tissue staining for Helicobacter pylori in subjects with atrophic body gastritis. Gastroenterology, 101, 167–174.
123
ORIGINAL PAPER
An Association Study of Histological Types of Gastric Carcinoma with Helicobacter pylori Infection Xia Wang • Muxin Wei • Zhiguang Sun
Ó Springer Science+Business Media New York 2014
Abstract The aim of this study was to study the relation between histopathological classification of gastric carcinoma and Helicobacter pylori (H. pylori) infection. 200 patients with confirmed gastric carcinoma between January 2010 and January 2012 from our hospital were included. All these patients went through endoscopy and histological examinations for gastric carcinoma and immunological test for H. pylori infection. Patients were grouped according to the histological classification, and the infection rates of H. pylori in different groups were compared. Types of gastric cancer that was closely related to H. pylori infection were identified. Infection rate in patients with the intestinal type of gastric cancer was significantly higher compared to those with the diffuse type. For tubular type of carcinoma, the well to medium-differentiated group had a significantly higher infection rate than the poorly differentiated group. Helicobacter pylori infection and histological types were relevant. The effect of H. pylori infection on the intestinal type was more significant than that on the diffuse type. The infection rate of well-differentiated group was higher than that of the poorly differentiated group, which suggested an association between H. pylori infection and the degree of differentiation of tubular cancerous tissue. X. Wang Nanjing University of Traditional Chinese Medicine, Nanjing, China X. Wang M. Wei Department of Chinese Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China Z. Sun (&) Jiangsu Provincial Hospital of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing 210029, China e-mail: [email protected]
Keywords Gastric cancer H. pylori Histological classification
Introduction Although there has been a progressive decline in the incidence of gastric carcinoma all over the world, it remains the fourth most common malignancy worldwide and the second most prevalent in China [1–3]. Among 934,000 new cases each year, China accounts for 42 %, with morbidity and mortality rate twofold more than that globally [4]. The most direct etiological association of gastric carcinoma has been established with Helicobacter pylori (H. pylori). H. pylori were declared a type-1 carcinogen by the International Agency for Research on Cancer (IARC) [5]. Several epidemiologic studies provide evidences for the role of H. pylori in the pathogenesis of gastric carcinoma [6–8]. A 10-year follow-up study with a total of 1,228 gastric cancer cases showed a sixfold increase in relative risk of gastric carcinoma [8]. Furthermore, H. pylori eradication treatment was associated with reduction in the risk of gastric carcinoma [7]. In the animal study with Mongolian gerbils, it was demonstrated that long-term infection with H. pylori induces adenocarcinoma in Mongolian gerbils, and all induced tumors consisted of welldifferentiated intestinal-type epithelium [9]. Human studies on the association between different histological types of gastric carcinoma with H. pylori infection have been conflicting [10–13]. In this study, we aimed to investigate the relationship between gastric carcinoma and H. pylori infection based on histological types, and to further study the association between H. pylori infection with gastric carcinoma of various degree of differentiations.
123
Cell Biochem Biophys
Methods
Table 1 Histological classification by Lauren’s criteria and WHO standard
Patients and Grouping
Histological type
Two hundred patients with proven gastric carcinoma diagnosed at our hospital between January 2011 and June 2013 were included in this study. All patients underwent an upper gastrointestinal endoscopy, with biopsy specimens obtained from the tumor. Gastric carcinoma was diagnosed, and the degree of differentiation was assessed by an experienced pathologist.
Histological types of gastric carcinoma by Lauren’s criteria
Histological Assessment and Grouping Gastric biopsy specimens were obtained endoscopically from the tumor site under direct vision in all subjects. Biopsy specimens were fixed overnight in buffer formalin, embedded in paraffin, cut to 4-lm thickness, and then stained with hematoxylin and eosin for observation. The gastric carcinomas were classified histologically on the basis of two standards: the Lauren’s criteria [14] and WHO standard [15]. In accordance with the Lauren criteria, gastric carcinoma was categorized into intestinal, diffuse, and unclassified types. Under the WHO classification, gastric carcinoma was classified into tubular, mucinous, papillary, signet ring cell, adenosquamous, carcinoid carcinoma, and the rest of other types. Since tubular carcinoma accounts for most of the gastric carcinoma, it was further divided into subtypes according to the degree of differentiation. Detection of H. pylori Infection Blood sample was collected from all patients, and H. pylori infection was examined by detecting IgG antibody to this organism by enzyme-linked immunosorbent assay (ELISA). Statistical Analysis Statistical analysis was performed on SPSS17.0. v2 test was carried out to test the correlation between the histological typing and the H. pylori infection rate.
n (%)
Intestinal
39 (19.5)
Diffuse Indeterminate
125 (62.5) 36 (18)
Histological types of gastric carcinoma by WHO standard Tubular Well differentiated
147 (73.5 %) 3
Well to medium differentiated
14
Medium differentiated
26
Medium to poor differentiated
38
Poor differentiated
66
Mucinous
42 (21 %)
Papillary
2 (1 %)
Signet ring cell Adenosquamous
4 (2 %) 2 (1 %)
Carcinoid
1 (0.5 %)
Others
2 (0.5 %)
According to Lauren’s criteria, 39 cases (19.5 %) of gastric cancer were classified as intestinal type and 125 (62.5 %) as diffuse type. The remaining 36 (18 %) were unclassified. Under the WHO classification, 147 (73.5 % of 200 cases) cases were of tubular carcinoma, 42 cases (21 %) were of mucinous carcinoma, 2 cases (1 %) were of papillary carcinoma, 4 cases (2 %) were of signet ring cell carcinoma, 2 cases (1 %) were of adenosquamous carcinoma, 1 case (0.5 %) were of carcinoid, and the rest (1 %) were of other types. Among 147 case of tubular carcinoma, it was further divided into subtypes: 3 cases were of well differentiated, 14 cases were of well-medium differentiated, 26 cases were of medium differentiated, 38 cases were of medium-poorly differentiated, and 66 cases of poorly differentiated. In total, 92 out of 200 (46 %) patients were tested positive with H. pylori based on ELISA. H. pylori Infection Rate Compared Across the Subtypes Classified by the Lauren’s Criteria
Results Patient Characteristics The mean age of the 200 patients with gastric carcinoma was 59.9 years old, with the range of 30–79 years old. There were 70 males (35 %) and 130 females (65 %). Patients were categorized into groups based on Lauren’s classification and WHO classification as shown in Table 1.
123
The relationship between H. pylori infection and the histologic type of gastric cancer based on Lauren’s criteria is shown in Table 2. Infection rate was significantly higher in the intestinal type of gastric cancer compared with the diffuse type (P \ 0.05). No significant difference was found in the infection rates between diffuse and indeterminate types and between intestinal and indeterminate types.
Cell Biochem Biophys Table 2 H. pylori infection rate of subtypes classified by Lauren’s criteria
Table 4 H. pylori infection rate of different subtypes of tubular carcinoma based on degree of differentiation
Lauren’s classification
Degree of differentiation
H. pylori negative
H. pylori positive
Total number of cases
Infection rate
Well/WellMedium/ Medium
17
26
43
60.5 %
H. pylori negative
H. pylori positive
Total number of cases
Infection rate
Intestinal type
16
23
39
58.9 %*
Diffuse type
74
51
125
40.8 %*
Indeterminate type
18
18
36
50 %
v2
8.40*
P value
\0.05*
Medium-poor
18
20
38
52.6 %
Poor
44
22
66
33.3 %
v2 P value
H. pylori Infection Rate Compared Across the Subtypes Classified by WHO Standard The relationship between H. pylori infection and the histological types of gastric cancer based on WHO standard is shown in Table 3. Tubular and mucinous cancer account for most of the cases in the cohort (94.5 %), which made it meaningless to compare these two subtypes to the rest of subtypes. Thus, only tubular and mucinous types were compared, and no significant difference was found in the infection rate between these two. H. pylori Infection Rate Compared Across the Subtypes of Tubular Type Based on Degree of Differentiation The infection rates among tubular types of different differentiations were significantly different (P \ 0.05), as shown in Table 4. The infection rates increased proportionally with the degree of differentiation, with the lowest infection rate at the poorly differentiated and the highest in the well differentiated. Exemplary histological images of tubular gastric carcinoma with different degrees of differentiation are shown in Fig. 1.
Table 3 H. pylori infection rate of subtypes classified by WHO standard WHO classified subtype
H. pylori negative
H. pylori positive
Total number of cases
Infection rate
Tubular
79
68
147
46.2 %*
Mucinous
21
21
42
50 %*
Papillary
1
1
2
50 %
Signet ring cell
3
1
4
25 %
Adenosquamous
2
0
2
0
Carcinoid
1
0
1
0
Other types
2
0
2
0
v2 P value
0.13* [0.05*
12.41 \0.05
Discussion Two classification systems are commonly used for histological categorization of gastric carcinoma. Lauren first categorized gastric carcinoma into two major subtypes: intestinal and diffuse subtypes based on microscopic appearance and growth patterns [14]. The intestinal type resembles normal intestinal mucosa, while diffuse type consists of discohesive poorly differentiated cells without recognizable gland formation. The 2010 WHO classification recognizes four major histologic patterns of gastric cancers: tubular, papillary, mucinous, and poorly cohesive (including signet ring cell carcinoma), plus uncommon histologic variants (15). The classification is based on the predominant histologic pattern of the carcinoma. In our study, 200 patients were grouped under both standards; the relationship between different histological types of gastric carcinoma and H. pylori infection was investigated. Helicobacter pylori infection is implicated in the pathophysiology of gastric carcinoma [6, 10, 11]. Now, it is generally believed that H. pylori induce a chronic inflammation in stomach, which ultimately progresses into atrophic gastritis. Atrophic gastritis and intestinal metaplasia are considered to be the precursor lesions of the intestinal type of gastric cancer [9]. Earlier studies also indicated that there are important clinical, histological, and demographic differences between intestinal and diffusetype gastric cancer. It is generally accepted that intestinaltype gastric carcinoma is related to atrophic gastritis [13, 16]. Our data show that infection rate was significantly higher in the intestinal type of gastric cancer compared with the diffuse type (P \ 0.05), which is consistent with the observations from others [11, 12]. We did not find any correlation of H. pylori infection with histological types of gastric carcinoma based on the WHO classification. However, our data suggested that there is a relationship between H. pylori infection and gastric carcinoma differentiation, with the lowest infection rate at the poorly differentiated and the highest in the well
123
Cell Biochem Biophys
Fig. 1 Histological image of tubular adenocarcinoma with different degrees of differentiation. a well differentiated; b medium differentiated; c poorly differentiated tubular adenocarcinoma
differentiated in the tubular type of gastric carcinoma. This result is reasonable considering the differentiated and undifferentiated types in our classification corresponded well with the intestinal and diffuse types of Lauren’s criteria. Helicobacter pylori positive rate of 46 % in our study is relatively low compared with other studies; however, geographic difference should be taken into consideration when making such comparison. Data obtained from more than 50 counties of rural China revealed that the proportion of the population positive for H. pylori antibodies varied from 26 to 96 % [17]. Studies that have examined the relationship between gastric cancer and H. pylori infection also showed a great variability [18]. Karnes et al. reported that prolonged atrophy may cause the spontaneous disappearance of H. pylori from the gastric mucosa and a fall in the antibody titer [19], which may also account for the variability. In summary, H. pylori infection and histological types were related. The effect of H. pylori infection on the intestinal type was more significant than that on the diffuse type. The infection rate of well-differentiated group was higher than that of the poorly differentiated group, which suggested an association between H. pylori infection and the degree of differentiation of gastric carcinoma. Acknowledgments This study was funded by Provincial Bureau of Traditional Chinese Medicine of Jiangsu, fund project #LZ13247.
References 1. Cancer (Fact Sheet No. 297) (February 2014). World Health Organization. Retrieved May 11, 2009. 2. Jemal, A., Bray, F., Center, M. M., Ferlay, J., Ward, E., & Forman, D. (2011). Global cancer statistics. CA: A Cancer Journal for Clinicians, 61(2), 69–90. 3. DeVita, V. T., Lawrence, T. S., Rosenberg, S. A., DePinho, R. A., & Weinberg, A. (2011). Principles and practice of oncology (9th ed., North American Edition ed.). Philadelphia, PA: Lippincott Williams & Wilkins.
123
4. Yang, L. (2006). Incidence and mortality of gastric cancer in China. World Journal of Gastroenterology, 12(1), 17–20. 5. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. (2010). IARC monographs on the evaluation of carcinogenic risks to humans. Ingested nitrate and nitrite, and cyanobacterial peptide toxins. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, 94, 1. 6. Parsonnet, J., Friedman, G. D., Vandersteen, D. P., Chang, Y., Vogelman, J. H., Orentreich, N., et al. (1991). Helicobacter pylori infection and the risk of gastric carcinoma. New England Journal of Medicine, 325, 1127–1131. 7. Fuccio, L., Zagari, R. M., Eusebi, L. H., Laterza, L., Cennamo, V., Ceroni, L., et al. (2009). Meta-analysis: Can Helicobacter pylori eradication treatment reduce the risk for gastric cancer? Annals of Internal Medicine, 151(2), 121–128. 8. Webb, P. M. (2001). Gastric cancer and Helicobacter pylori: A combined analysis of 12 case control studies nested within prospective cohorts. Gut, 49(3), 347–353. 9. Watanabe, T., Tada, M., Nagai, H., Sasaki, S., & Nakao, M. (1998). Helicobacter pylori infection induces gastric cancer in Mongolian gerbils. Gastroenterology, 115(3), 642–648. 10. Loffeld, R. J. L. F., Willems, I., Flendrig, J. A., & Arends, J. W. (1990). Helicobacter pylori and gastric carcinoma. Histopathology, 17, 537–541. 11. Parsonnet, J., Vandersteen, D., Goates, J., Sibley, R. K., Pritikin, J., & Chang, Y. (1991). Helicobacter pylori infection in intestinal- and diffuse-type gastric adenocarcinomas. Journal of the National Cancer Institute, 83, 640–643. 12. Martı´n-de-Argila, C., Boixeda, D., Redondo, C., Alvarez, I., Gisbert, J. P., Garcı´a Plaza, A., et al. (1997). Relation between histologic subtypes and location of gastric cancer and Helicobacter pylori. Scandinavian Journal of Gastroenterology, 32(4), 303–307. 13. Komoto, K., Haruma, K., Kamada, T., Tanaka, S., et al. (1998). Helicobacter pylori infection and gastric neoplasia: Correlations with histological gastritis and tumor histology. American Journal of Gastroenterology, 93(8), 1271–1276. 14. Lauren, P. (1965). The two histological main types of gastric carcinoma, diffuse and so-called intestinal-type carcinoma: An attempt at a histo-clinical classification. Acta Patholog Microbiology Scand, 64, 31–49. 15. Lauwers, G. Y., Carneiro, F., & Graham, D. Y. (2010). Gastric carcinoma. In F. T. Bowman, F. Carneiro, & R. H. Hruban (Eds.), Classification of tumours of the digestive system. Lyon: IARC.
Cell Biochem Biophys 16. Talley, N. J., Zinsmeister, A. R., Weaver, A., et al. (1991). Gastric carcinoma and Helicobacter pylori infection. Journal of the National Cancer Institute, 83, 1734–1739. 17. Forman D, Sitas F, Newell DG, Stacey, AR Boreham J, Peto R, Campbell TC, Li J, Chen J. Geographic association of Helicobacter pylori antibody prevalence and gastric cancer mortality in rural China. International Journal of Cancer. 46(4), 608 ISSN 0020-7136, 10/1990.
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