Relationship between Gastric Cancers and Trio of Helicobacter Pylori Infection , Chronic Gastritis and Gastric Mucosal Intestinal Metaplasia as seen in Jos University Teaching Hospital , Nigeria

Background: In 1994 Helicobacter pylori was classified as class 1 human carcinogen by the IARC (WHO), based on epidemiological evidence. Experimental evidence was subsequently provided by Wantabe et al. This has triggered several studies on the prevalence of H. pylori in patients with Gastric cancers in various regions of the world. In Africa the infection rate in various populations as reported by some studies are not parallel to the incidence of morbidity caused by this infection. Objective: To determine the relationship between Helicobacter pylori infection, Chronic gastritis, Gastric mucosal intestinal metaplasia with Gastric cancers. Methodology: This was a retrospective histopathological study of all gastric cancers with adjacent non – cancerous epithelium seen between January 2005 and December 2012 in the department of Histopathology, Jos University Teaching Hospital (JUTH). Blocks and archival slides were used for the


Introduction
Evidence of a spiral-shaped gram negative bacterium in the stomach of animals and humans was first known at the end of the 19 th century but was dismissed as incidental. 1 In the year 1983, two Australian physicians, Robin Warren and Barry Marshal isolated spiral-shaped Gram negative bacteria from the stomachs of patients with gastritis and peptic ulcer. 2 The organism was originally named Campylobacter pyloridis but was later given a new genus, Helicobacter and was named Helicobacter pylori. 3In 1994 H. pylori was classified as class 1 human carcinogen by the IARC (WHO), based on epidemi ological evidence. 4xperimental evidence was subsequently provided by Wantabe et al. 5 .The identification of H. pylori in gastric epithelium and its classification as a human carcinogen in relation to Gastric Adenocarcinoma triggered

ORIGINAL ARTICLE
several studies on the prevalence of H. pylori in patients with Gastritis and Gastric and West in Lei cester, United Kingdom reported 43% prevalence of H. Pylori in gastric carcinoma with no significant difference between intestinal and diffuse types. 7In that tudy no association was seen between the prevalence of H. pylori and tumour location or intestinal metaplasia, but the relationship between Carcinoma and gastritis was significant.In Pakistan and Saudi Arabia, Muhammad et al. 8 and Jamal et al. 9 reported a prevalence of 70% and 79.8% respectively.Komolafe et al. 10 in Ile-Ife, south western Nigeria reported 60%. 10 These values are however higher than 15% reported by Abdulkareem et al. 11 in Lagos and 17.9% reported by Oluwasola and Ogunbuyi 12 at Ibadan, both in south western Nigeria.In the study by Oluwasola et al. 12 , moderate to severe gastritis was seen in 91.7% of cases, there was no significant difference between the prevalence of H. pylori in the intestinal and diffuse type of gastric carcinoma, while intestinal metaplasia was seen in 41.7% of cancers.Abdulkareem et al. 11 in Lagos and Komolafe et al. 10 in Ile-Ife also reported the presence of gastritis in 64% and 75% of their case respectively.Chronic gastritis precedes intestinal metaplasia in gastric carcinogenesis; this made it an important finding.Oluwasola et al in Ibadan, reported intestinal metaplasia in 41.7% of cases in their study while Komolafe et al. in Ile-Ife and Abdulkareem et al in Lagos reported 16% and 22% respectively.In the year 2002 almost 20% of cancers were considered to be attributable to infectious diseases, with H. pylori leading the cause (5.5% of all cancers) 13 .H. pylori is estimated to be responsible for about 65% of all stomach cancers worldwide, comprising of 75% of Non-cardia gastric carcinoma and gastric lymphomas13.H. pylori infection is said to be the commonest chronic bacterial infection in the world.More than half of the world's population in both developing and developed countries are infected with this organism1 4 .Its prevalence in the US is 52% and ranges between 80-90% in developing countries.The route of infection is not known, but it was suspected that it enters the stomach by being ingested in food or water 15 .Interestingly however, in Africa the infection rate in various populations does not parallel the incidence of morbidity caused by the infection 15 .This has been termed by a number of authors as the 'African enigma' based on an apparently low incidence of gastric carcinoma and other H. Pylori-associated morbidities in the continent of Africa 16 .This concept has been challenged, and suggestion that the enigma could be explained by lack of infrastructure and access to hospitals and care in African countries thereby resulting to incomplete reporting of gastric cancers.Another criticism on the African enigma has been the high prevalence of HIV infection.A relatively large population will die before the age in which gastric cancer becomes frequent 16 .Similar discordance between H. pylori infection and gastric carcinoma prevalence has also been reported within the Asian continent 17 .However, previous study by Kwaghe et al. 18 , looked at the clinicopathological characteristics of gastric malignanacies.Therefore, this study aimed to determine the relationship between Helicobacter pylori infection, Chronic gastritis and Gastric mucosal intestinal metaplasia with Gastric cancers

Materials and Methods
This was a retrospective study of all Gastric cancers with adjacent non -cancerous epithelium, seen in the department of Histopathology Jos University Teaching Hospital, between January 2005 and December 2012.Paraffin wax embedded tissue blocks and corresponding archival routine haematoxylin and eosin (H&E) stained slides of all gastric cancer cases were retrieved and reviewed.Fresh sections were taken where original slides were missing or damaged and Modified Giemsa stain was used to identify the presence of H. pylori organisms in the non-cancerous gastric mucosa adjacent to these malignancies.Immunohistochemistry using c-KIT, SMA (smooth muscle actin) and CD34 antibodies was done on seven mesenchymal malignancies.

Results
Malignant gastric tumours accounted for 79 cases, representing 4.19% of the 1883 malignant tumours recorded in Histopathology department J.U.T.H. over the study period.Out of the 79 gastric cancers seen within the study period, 46 cases had adjacent non-cancerous epithelium and were included in the study.This comprises of 38 cases of Adenocarcinoma, 6 cases of gastrointestinal tumour (GIST), a case of carcinoid and a case of leiomyosarcoma, that was positive for SMA, but negative for c-KIT and CD34.These were analysed for evidence of gastritis, intestinal metaplasia and the presence of H. pylori.Chronic gastritis was seen in 33 (71.7%) cases.All these were Adenocarcinoma cases, thus 86.6% of adenocarcinoma cases with adjacent noncancerous epithelium had chronic gastritis (Table 1).Sixteen (34.8%) had moderate Gastritis, fourteen (30.4%) had severe gastritis, 10 (21.7%) had mild gastritis, while 6 (13.0%) were normal.Intestinal metaplasia was present in adjacent normal epithelium of 14 cases, i.e. 30.4% of all tumours in the study.Intestinal metaplasia was not seen in the adjacent non-cancerous epithelium of other tumour types (Table ).The presence of H. Pylori was seen in only 7 (15.2%)cases of all the Gastric malignancies.However, the percentage of Helicobacter pylori in Adenocarcinoma cases is 18.4%.The presence of H. pylori based on Lauren classification was 3 (27.3%)and 4 (14.8%) for the diffuse and intestinal types respectively.These values are however lower than 43% reported in United Kingdom, 70% in Pakistan and 79.8% in Saudi Arabia. 6,8,9The low association of gastric cancers and H. Pylori seen in this study may be The the relationship between H pylori and gastric cancer was not significant.This may be attributable to the advanced tumour stages in which most of our patients presented and also the fact that most of the specimens were endoscopic biopsies containing mostly the tumour with very little adjacent non-cancerous epithelium.

Conclusion:
Gastric cancer showed a significant relationship with chronic gastritis and gastric mucosal intestinal metaplasia as seen in the other studies, however there was no significant relationship between gastric cancer and H. pylori infection.

Table 1 : Distribution of Chronic gastritis, intestinal metaplasia and H. pylori in adjacent non- cancerous gastric epithelium of Gastric cancers seen in J.U.T.H., Jos
H. pylori seen in the adjacent normal gastric epithelium of a gastric cancer case.(Modified giemsa x 400)

Figure 2 .
11,11ic cancer seen with background chronic gastritis (H and E x 100) Discussion Forty-six cases of cancers seen within the study period had adjacent non-cancerous epithelium, this comprises of 38 Adenocarcinoma cases and 8 cases of other tumours.Chronic gastritis was seen in 33 (71.7%) cases.This concurs with the work of Komolafe et al. in Ile-Ife and Abdulkareem et al. in Lagos Nigeria who reported 64% and 75%respectively10,11.This shows that there is a strong relationship between Gastric cancer and chronic gastritis which might have been caused by chronic 7% reported by Komolafe et al.10in Ile-Ife and higher than 16% reported by Oluwasola et al.12in Ibadan.H. Pylori is said to be responsible for 65% of all gastric cancers seen worldwide.The presence of H. pylori was seen in 7 cases of gastric Adenocarcinoma, i.e 15.2% of all the gastric malignancies seen in the study.No H. pylori seen in cases with other tumour types apart from Adenocarcinomas.This corresponds closely with 15% reported by Abdulkareem et al.11and 17.9% reported by Oluwasola et al.
H. Pylori infection or Autoimmunity.Intestinal metaplasia was seen in 14(30.4%)cases of all denocarcinoma cases.This is comparable to 22% reported byAbdulkareem et al. 11in Lagos, but significantly lower than 41.