Analysis of Basement Membrane Structure and Inflammation During the Development of Esophageal Squamous Cell Carcinoma in the Chinese Chaoshan High Risk Region

Abstract

Background & Aims: To investigate relationships between basement membrane structure, inflammation, β1 integrin expression, activation of ERK/MAPK signaling pathways, and cell proliferation in esophageal mucosa at various stages during the evolution of esophageal squamous cell carcinoma. Methods: Three tissue arrays were made of 228 tissue cores from 428 surgically-resected specimens. The arrays included 26 samples of normal epithelium, 28 with hyperplasia, 18 with dysplasia, 27 with carcinoma in situ and 129 with invasive carcinoma. In addition, 21 cases of hyperplasia, 13 cases of dysplasia and 13 case of carcinoma in situ were obtained by manual microdissection of unfixed frozen tissue. Hematoxylin and eosin stained sections were used to evaluate the epithelium and inflammation. The periodic acid-Schiff stain and an immunohistochemical stain for laminin were used to examine the structure of basement membranes. The expression of β1 integrin, p-ERK, and Ki67 were evaluated by quantitative immunohistochemistry. RT-PCR and Western blots were also used to detect expression of β1 integrin. Results: Quantitative scales were developed to classify basement membrane structure and inflammation. Basement membrane alterations correlated with the degree of epithelial change (χ² = 501.9, p < 0.01) and with the degree of lymphocytic infiltration in the lamina propria and epithelium (χ² = 273.4, p < 0.01). There was a significant relationship between the extent of basement membrane alteration and the expression of β1 integrin, p-ERK, and Ki67 Conclusions: The correlations suggest that there is a direct relationship between basement membrane structure and the development of esophageal squamous cell carcinoma.

Keywords:

• Basement membrane
• Inflammation
• ERK/MAPK signaling pathway
• Ki67
• Esophageal carcinogenesis

ABBREVIATIONS
ERK	=	extracellular signal-regulated kinase
p-ERK	=	phosphorylation extracellular signal-regulated kinase
MAPK	=	mitogen-activated protein kinase
Ki67	=	a nuclear protein expressed in proliferating cells, a mark of proliferative activity

ABBREVIATIONS
ERK	=	extracellular signal-regulated kinase
p-ERK	=	phosphorylation extracellular signal-regulated kinase
MAPK	=	mitogen-activated protein kinase
Ki67	=	a nuclear protein expressed in proliferating cells, a mark of proliferative activity