Histopathology examination of esophageal tissues
Histopathological changes of H&E-stained tissues of the esophageal mucosa were examined. Squamous epithelium of all control untreated rats showed esophageal mucosa with hyperkeratosis and squamous hyperplasia (Figure 2A). The squamous epithelium from all rats treated with carcinogen showed hyperkeratosis and patchy areas of mild squamous dysplasia (Figure 2B) and severe squamous dysplasia (Figure 2C). In addition, well-differentiated keratinizing squamous cell carcinoma was detected (Figures 2D & E).
Histopathology examination of gastric tissues
The gastric mucosa from the body and the antrum of all control untreated rats was within normal limits (Figures 2F & G, respectively). Squamous hyperplasia, dysplasia, or carcinoma was not observed in the control tissues. In contrast, gastric mucosa from carcinogen-treated rats showed hyperplastic mucinous glands and mild squamous dysplasia (Figure 2H). In addition, invasive adenocarcinoma was detected (Figure 2I). Conversely, the tissues from carcinogen plus MRN-100-treated rats showed patchy and small areas of mild squamous dysplasia in only 7/20 tissues. Thus, it appeared that MRN-100 decreased the extent of esophageal dysplasia and squamous cell carcinoma. Similar findings were also noted for gastric dysplasia and adenocarcinoma.
Figure 2
H&E histopathology staining from esophageal and gastric tissues. The foci of dysplasia and carcinoma are patchy and involved 1 to 2 mm of the tissue sections. (A) Section of a control rat's esophageal tissue, there is hyperkeratosis (down arrow) and squamous hyperplasia (up arrow) (2X). (B-E) Sections from esophageal mucosa from carcinogen-treated rats. (B) Section of esophagus showing a focus of mild squamous dysplasia (up arrow) (10X). (C) Section of esophagus showing severe squamous dysplasia (10X). (D) Section of esophagus showing a focus of mild, moderate, and severe squamous dysplasia (down arrow) and a focus of squamous cell carcinoma (up arrow) (4X). (E) Section of esophagus showing invasive well-differentiated keratinizing squamous cell carcinoma (10X). (F) Section of the stomach body of a control rat (4X). (G) Section of the antrum of the stomach of a control rat (4X). (H,I) Sections from gastric tissues of carcinogen-treated rats. (H) Section of antrum area showing mild dysplasia of glands (up arrow) and hyperplastic mucinous glands (down arrow) (4X). (I) Section of the body showing high-grade glandular dysplasia (down arrow) and invasive adenocarcinoma (up arrow) (4X).