Use of Ghrelin and Telomerase Activation for Diagnosis of Early-stage Gastric Cancers and Development of Treatment

2003 Fiscal Year Final Research Report Summary

• Project/Area Number: 14570520
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: KANAZAWA MEDICAL UNIVERSITY
• Principal Investigator: ITOH Tohru Kanazawa Medical University, Associate Professor, 医学部, 助教授 (80193499)
• Co-Investigator(Kenkyū-buntansha): KANDA Tugiyasu Kanazawa Medical University, Professor, 医学部, 教授 (40261838)
• Project Period (FY): 2002 – 2003
• Keywords: Early gastric cancer / Lymph node metastasis / Endoscopic treatment / Telomerase activity / Ghrelin / Enzyme-immunohistochemistry / Real-time PCR / hTRT mRNA

Research Abstract

Since metastasis in lymph nodes increases with invasion of carcinoma cells, endoscopic diagnosis of the depth of invasion of carcinoma cells using a visual or ultrasonic endoscope, and metastasis in lymph nodes presumed to exist based on the results of an endoscopy are critical factors for determining the method of treatment for early-stage gastric cancers. Although operative endoscopy is appropriate for most mucosal carcinomas (m-cancers) in the early stage of gastric cancer, for submucosal carcinomas (sm-cancers), surgical resection has been conducted in many cases, and alternative treatment methods using an endoscope have been sought for sm-cancers. We sought an effective auxiliary diagnosis method for determining the treatment. We studied 122 cases of patients with submucosal carcinomas who had surgical operations in our hospital. We examined the cases for which satisfactory specimens were obtained through biopsy and resection of lesion for oncogene expression and human telomerase reverse transcriptase.
Oncogene expression:
We conducted immunohistochemical staining using antibodies of c erb2 c met nm23 FTS -1 APC gene and telomerase (k-67) to examine for oncogene expression in the biopsy and resection specimens. Although there is some relevance for expression of carcinoma cells by each antibody in biopsied specimens and resected specimens, there is no significant difference in the loss of antigenecity in the resected specimen by formalin embedded fixation, and in the expression of carcinoma cells whether each carcinoma cell has heterogeneity. In the comparison of the invasion depths of carcinoma cells between sm-1 and sm-2, expression of c erb2 c met nm23 FTS -1 APC gene and telomerase (k-67) in sm-2 was stronger than that in sm-1. There was no specific tendency in histopathological classification (differentiated or undifferentiated carcinomas).
Human telomerase reverse transcriptase:
Human telomerase reverse transcriptase mRNA was measured using real-time PCR, and values measured by a spectrophotometer were compared with the value of the standard RNA to calculate the quantitative value of hTRT and mRNA. There is no significant relationship between metastasis in lymph node based on the invasion depth (sm-1 and sm-2) and these factors : 1) quantitative difference of ghrelin and telomerase activation, 2) comparison of expression of carcinoma cells in sm-1 and sm-2 by immunoenzymatic technique using oncogene antibodies for 3) histopathological texture and expression of ghrelin (by immunoenzymatic technique).
Consequently, although the expression of carcinoma cells in the biopsied and resected specimens can be an auxiliary factor in speculation about the existence of lymph-node metastasis of early-stage gastric cancers, there was no significant relationship with a quantitative difference in the expression of human telomerase reverse transcriptase mRNA. This is an issue for future study.