Gastric cancer is the fourth most prevalent malignancy in the world. In Egypt, it is in the eleventh rank among all cancers. It is a multifactorial disease. Helicobacter pylori infection is an essential risk factor in most of sporadic gastric carcinoma cases. While hereditary diffuse type is more likely to have a primary genetic etiology.
Human epidermal growth factor receptor 2 (Her2/neu) is a proto-oncogene, belonging to the epidermal growth factor receptor (EGFR) family. It is thought to evoke a cascade of events that end in sustained cell proliferation and inhibition of apoptosis.
The metastasis-promoting protein; S100A4 belongs to the S100 family of structurally related calcium binding proteins. It has a variety of functions including regulation of calcium homeostasis, cell proliferation and migration.
This retrospective study was carried upon 70 cases of gastric adenocarcinoma. Additional three different non-malignant lesions, adjacent to gastric adenocarcinoma, were also included in the study. Those adjacent non-malignant lesions included 28 chronic gastritis, 9 intestinal metaplasia and 16 gastric dysplastic lesions. Six cases of apparently normal gastric tissue were used as a control group.
Histopathological examination was done for each case of gastric carcinoma to assess the histopathological type (according to WHO 2010), the grade, the depth of invasion of the tumor as well as intratumeral neutrophilic infiltration. Giemsa stain was performed for assessment of H.pylori presence in chronic gastritis lesions adjacent to carcinoma.
Avidin_Biotin complex technique using anti-Her2/neu and anti-S100A4 was applied for each case, and examined to assess their expression. Correlations between Her2/neu as well as S100A4 expression and different clinicopathological variables were done.
Median age of studied gastric carcinoma cases was 54.5 years. Gastric cancer rates were about twice as high in males as in females.
Each case was staged according to TNM staging system and there was a statistically positive correlation between TNM stage and grades of studied gastric carcinoma cases.
H.pylori was detected only in chronic gastritis lesions. Most of the positive cases were adjacent to tubular adenocarcinoma. However, it was not detected either in studied intestinal metaplasia, dysplastic or malignant lesions.
A statistically significant positive correlation was found between tumor-infiltrating neutrophils (TINs) count and positivity for H pylori in adjacent chronic gastritis as well as TNM stage of gastric cancer.
Human epidermal growth factor receptor 2 (Her2/neu) was not expressed in normal gastric tissue. However its expression increased gradually in progression throughout adjacent precancerous lesions to be the highest in gastric adenocarcinoma suggesting a possible role of Her2/neu in the gastric carcinogenesis.
There were statistically significant positive correlations between Her2/neu expression and advanced tumor grade as well as presence of H pylori in adjacent chronic gastritis. While no significant correlation was detected between Her2/neu expression and histological types, TNM stage of gastric cancer or TINs.
S100A4 was not expressed in normal gastric tissue. However its expression increased gradually in progression from chronic gastritis to intestinal metaplasia to low grade dysplasia to high grade dysplasia to be the highest in gastric adenocarcinoma indicating that upregulation of S100A4 may play an important role in the gastric malignant transformation.
No relation was demonstrated between S100A4 expression and either histologic type, advanced tumor grade or presence of H pylori. While there were statistically significant positive correlations between its expression and both TNM stage and TINs count.
The current study revealed a possible link between Her2/neu expression and S100A4 upregulation as there was a statistically significant positive correlation between them. |
