Expression of hMSH2 in human esophageal cancer from patients in a high incidence area in Henan, China

Abstract

AIM: DNA repair enzymes are important in maintaining genomic stability by limiting the rate of mutation. The genetic alteration of mismatch repair genes (e.g., hMSH2) has been identified in association with the development of hereditary nonpolyposis colorectal cancer. The present study was undertaken to investigate a possible role of HMSH2 alteration in causing esophageal cancer in a high-risk population from Henan, China.

METHODS: Twenty-two cases of human esophageal squamous cell carcinoma from a high incidence area for esophageal cancer in Henan were analyzed immunohistochemically (ABC) for the expression hMSH2 repair enzyme.

RESULTS: The hMSH2 protein was detected in all 22 esophageal cancers and non-cancerous squamous epithelia. The hMSH2-positive cancer cells were mainly distributed in the peripheral cell layers of the well-differentiated cancer nests. In carcinoma in situ and poorly differentiated cancers, more than 90% of cancer cells showed positive immunostaining for hMSH2. Positive immunostaining was detected throughout the proliferation compartments of basal cell hyperplasia and dysplasia lesions. In the morphologically-normal squamous cell epithelia, hMSH2-positive cells were mainly located in the parabasal cell layers, while only “scattered” positive cells were observed in the basal cell layer. The staining intensity remained constant from the cancers to the non-cancerous epithelia. The hMSH2 immunostaining patterns coincided with those observed for the proliferation cell nuclear antigen (PCNA), with the exception that promitot ic and mitotic cells lacked hMSH2 immunostaining.

CONCLUSION: The present findings indicate that the occurrence of hMSH2 protein expression is associated with the cell cycles and related to PCNA expression, implying that the hMSH2 protein is expressed as a guardian in DNA-synthesizing cells. Assuming the immunodetected protein is normal hMSH2 enzyme, our results further suggest that hMSH2 alteration is not a frequent event among this high cancer risk population in Henan, China.

Key Words: Esophageal neoplasms; hMSH2; Colorectal neoplasms; DNA repair enzymes; Proliferation cell nuclear antigen