Clinical significance of Fhit expression in development of colorectal carcinoma of various macroscopic types.

Abstract

It is unclear how expression of the FHIT (fragile histidine triad) gene by the colorectal neoplasm correlates with histogenesis and progression of the disease. We studied the association between expression of Fhit protein and development of colorectal carcinoma (CRC). We also examined relations between Fhit protein expression, macroscopic type, Ki-67 labeling index (LI), and p53 overexpression in carcinoma in situ. We examined 27 colorectal adenomas, 82 carcinomas in situ and 21 invasive CRCs resected endoscopically or surgically. The carcinomas in situ comprised three macroscopic types: polypoid (n=27), superficial (flat elevated, n=27; depressed, n=10) and granulonodular laterally spreading tumor (G-LST, n=23). Fhit, Ki-67, and p53 overexpression were examined immunohistochemically. Levels of Fhit protein were lower in invasive CRC than in adenoma and carcinoma in situ (p<0.01). In carcinoma in situ, reduced Fhit expression was observed in 7 of 22 (31.8%) polypoid types, 13 of 27 (48.1%) superficial flat elevated types, 8 of 10 (80%) superficial depressed types and 7 of 23 (30.4%) G-LST. Frequencies of reduced Fhit expression were significantly higher in the polypoid type and G-LST lesions than in the depressed type (p<0.05). Reduced expression of Fhit protein was related significantly to Ki-67 LI and p53 overexpression in carcinoma in situ (p<0.01). The present findings suggest that reduced expression of Fhit protein is related to development of colorectal neoplasm. Polypoid CRC and G-LST appear to differ from superficial depressed CRC in terms of Fhit expression.

• Authors: Toshio Kuwai, Shinji Tanaka, Eijiro Kaio, Toru Hiyama, Masanori Ito, Yasuhiko Kitadai, Masaharu Sumii, Masaharu Yoshihara, Ken Haruma, Kazuaki Chayama
• Journal: International journal of molecular medicine (Int J Mol Med) Vol. 12 Issue 4 Pg. 437-42 (Oct 2003) ISSN: 1107-3756 [Print] Greece
• PMID: 12964015 (Publication Type: Journal Article)

Chemical References

• Ki-67 Antigen
• Neoplasm Proteins
• Tumor Suppressor Protein p53
• fragile histidine triad protein
• Acid Anhydride Hydrolases

Topics

• Acid Anhydride Hydrolases (biosynthesis, physiology)
• Adenoma (metabolism)
• Carcinoma (metabolism)
• Carcinoma in Situ (metabolism)
• Cell Line, Tumor
• Colorectal Neoplasms (metabolism)
• Humans
• Immunohistochemistry
• Ki-67 Antigen (biosynthesis)
• Neoplasm Proteins (biosynthesis, physiology)
• Ploidies
• Tumor Suppressor Protein p53 (metabolism)