Decreased fragile histidine triad expression in colorectal cancer and its association with apoptosis inhibition.
OBJECTIVE
To detect the expression of fragile histidine triad (FHIT) in normal colorectal tissue, colorectal adenoma and colorectal cancer (CRC) tissue, and to analyze its relationship with the clinicopathological features of CRC, and apoptosis-associated proteins (Bcl-2, Bax, survivin) and apoptosis in colorectal cancer.


METHODS
FHIT mRNA analysis was performed by nested reverse transcription-polymerase chain reaction (RT-PCR) assay. Tissue microarray (TMA) was established to detect the expression of FHIT, Bcl-2, Bax and survivin genes in 80 CRC tissue specimens, 16 colorectal adenoma tissue specimens and 16 hemorrhoid (PPH) tissue specimens during the same period of time as the control. Citrate-microwave-SP was used as immunohistochemical method. The relationship between clinicopathological factors, such as differentiation grades and 5-year survival rate was observed. TUNEL assay was used to detect the apoptosis index in 80 CRC tissue specimens.


RESULTS
Ten out of 26 (38.5%) CRC tissue specimens expressed aberrant FHIT transcripts, none of the aberrant FHIT transcripts was observed in the matched normal tissue and colorectal adenoma tissue by nested RT-PCR assay. The positive rate of FHIT gene expression in normal colorectal tissue, colorectal adenoma and carcinoma tissue was 93.75%, 68.75% and 46.25%, respectively. Clinicopathological analysis of patients showed that the decreased FHIT gene expression was not associated with age, sex, serum CEA levels, tumor site and size, histological classification. However, the expression of FHIT was correlated with differentiation grades, pathological stages, lymph node metastases and 5-year survival rate after operation. The positive rate of apoptosis-associated proteins (Bax, Bcl-2 and survivin) in CRC tissue was 72.50%, 51.25% and 77.50%, respectively. The expression of these apoptosis-associated proteins in CRC tissue was correlated with the expression of FHIT. The mean apoptosis index in FHIT negative tumors was significantly lower than that in FHIT positive tumors (5.41 +/- 0.23 vs 0.56 +/- 0.10, P < 0.01).


CONCLUSIONS
The FHIT gene plays an important role in the regulation of apoptosis and decreased FHIT expression plays a key role in the initiation and progression of colorectal carcinoma.
Cao
Jie
J
Department of Gastrointestinal Surgery, Affiliated Guangzhou First People's Hospital, Guangzhou Medical College, 1# Pang Fu Road, Guangzhou 510180, Guangdong Province, China. czhongt@126.com
Chen
Xiao-Ping
XP
Li
Wang-Lin
WL
Xia
Jie
J
Du
Hong
H
Tang
Wei-Biao
WB
Wang
Hui
H
Chen
Xi-Wen
XW
Xiao
Huan-Qing
HQ
Li
Yu-Yuan
YY
D017766:Acid Anhydride Hydrolases / Q000235:genetics / Q000378:metabolism*; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000236:Adenoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000502:physiology*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000077022:Survivin; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D000077022:Survivin; D051028:bcl-2-Associated X Protein; D000099170:Bis(5'-adenosyl)triphosphatase; C107489:BIRC5 protein, human