2272

FHIT

fragile histidine triad;FHIT;fragile histidine triad

AP3A hydrolase|bis(5'-adenosyl)-triphosphatase|diadenosine 5',5'''-P1,P3-triphosphate hydrolase|dinucleosidetriphosphatase|tumor suppressor protein

3p14.2

protein-coding

BACKGROUND & OBJECTIVE: Fragile histidine triad(FHIT), a tumor suppressor candidate gene, encompasses FRA3B, a common region with the highest fragility in the human genome, and is altered in a large number of human cancers, particularly those of epithelial cell origin and associated with known carcinogenic agents. The aim of this study was to investigate the expression of FHIT protein, Fhit and the possible relationship between Fhit expression and clinicopathological indices in breast cancer. METHODS: Fhit protein expression in 66 cases of formalin-fixed, paraffin-embedded breast cancer composed of 6 in situ and 60 invasive ductal carcinoma were detected with citrate-microwave-Streptavidin-HRP(SP) immunohistochemical method, using rabbit antibody to human FHIT gene protein and relationships to invasion and lymphatic metastasis were analyzed. RESULTS: Thirty-eight (57.6%) cases of carcinomas showed a marked loss or absence of Fhit expression compared with the adjacent non-cancerous breast tissues, in which 22 cases were negative. The remain 18 (27.3%) showed stronger than, and 10 (15.2%) equal to the Fhit expression of the adjacent non-cancerous tissue. The lower expression of Fhit was found in 20/24(83.3%) cases with local or axillary lymphatic metastasis, and in 18/36 (50%) cases without metastasis in the invasive ductal carcinoma. Fhit expression was determined in all 6 cases of in situ ductal carcinoma did not show lower than non-cancerous tissue. There was a significant difference in the expression of Fhit between the breast cancers with and without lymphatic metastasis, both in ductal carcinoma (P < 0.01) and in invasive ductal carcinoma(P < 0.01). CONCLUSIONS: The expression of Fhit is associated with invasion and metastasis of tumor in breast cancer. It is suggested that decreased Fhit expression may play an important role in the development and progression of the tumor, and thus may become a new prognostic marker for breast cancer.

OBJECTIVE: To investigate the relationship between the expression of fragile histidine triad (FHIT) protein and the clinicopathological characteristics of rectal carcinoma. The relationship between FHIT protein expression and Bcl-2, Bax and survivin expression, as well as cell apoptosis in rectal carcinoma were explored. METHODS: Tissue microarray and immunohistochemistry SP were used to detect the expression of FHIT, Bcl-2, Bax and Survivin in 16 cases of normal rectal tissue, 16 cases of rectal adenoma and 80 cases of rectal carcinoma. TUNEL was used to detect apoptosis index (AI) in 80 cases of rectal carcinoma. RESULTS: The positive rates of FHIT expression in normal rectal tissue, rectal adenoma and adenocarcinoma were 93.8%, 75.0% and 46.3% respectively. There were no significant differences between FHIT expression and histological types, gender and age (P>0.05). FHIT expression was significantly correlated with lymph node metastasis, Duke's stage and 5-year survival rate. The expression of FHIT was positively correlated with that of Bcl-2, Bax and survivin in rectal cancer. The mean AI in FHIT-negative tumors was significantly lower than that in FHIT-positive tumors (P<0.01). CONCLUSIONS: The reduction of FHIT protein expression may play an important role in the development of rectal carcinoma, and FHIT protein may be associated with the regulation of cell apoptosis.

OBJECTIVE: To investigate the expression of fragile histidine triad gene protein (Fhit) and the possible relationship between Fhit and biological behaviors of hypopharyngeal carcinoma. METHOD: The expression of Fhit protein in 66 cases with hypopharyngeal carcinoma were detected by rabbit antibody to human FHIT gene protein with SP immunohistochemical method. The relationship between historical grade and lymphatic metastasis were analysed. RESULT: (1) The positive expression rate of Fhit was 42.42% (28/66) in hypopharyngeal carcinoma, and 83.33% (55/66) in normal hypopharyngeal tissue, respectively. There was a significant difference in the expression of Fhit between the cancer tissue and normal tissue (P < 0.01). (2) The positive expression of Fhit in well, moderate, poor differentiated hypopharyngeal carcinoma were 65.38% (17/26), 38.10% (8/21) and 26.32% (5/19), respectively. There are significant statistic difference among them each other (P < 0.01). (3) The positive expression of Fhit was 75.00% (12/16) in the group without lymph node metastasis, and 36.00% (18/50) with lymph node metastasis. CONCLUSION: The expression of Fhit in hypopharyngeal squamous cell carcinoma lower than normal tissue. The expression of Fhit significantly associated with historical grade and lymphatic metastasis in hypopharyngeal squamous cell carcinoma. It suggested that the expression of Fhit decreased may plays an important role in the development and progression of the tumor, and thus may become a new prognostic marker in hypopharyngeal carcinoma.

CONCLUSION: Our findings show that copy number loss of FHIT is associated with lymph node metastasis (LNM) and suggest that the down-regulation of Fhit indicates poor prognosis in early oral squamous cell carcinoma (OSCC). OBJECTIVES: The purpose of this study was to identify alterations in genetic markers related to LNM in early OSCC. METHODS: Genome-wide copy number alterations were analyzed in 14 early OSCCs with (n = 7) or without (n = 7) cervical LNM using 180K array-comparative genomic hybridization. To explore the prognostic implications of the most significantly associated genetic alteration with cervical LNM, immunohistochemical analysis was conducted in 30 OSCCs. RESULTS: A total of 11 recurrently altered regions (RARs) were identified in the 14 OSCC cases. Six RARs on chromosomes 3p26-3p14, 5q22, and 9p21 were found to be significantly more common in early OSCC with LNM (p < 0.05). Among these, loss of 3p14.2 (where the FHIT gene is located) was the most frequent (five of seven patients with LNM, and none of seven without LNM), and most significantly associated with cervical LNM (p = 0.005). Fhit immunohistochemical staining of 30 OSCCs showed that Fhit negativity was associated with cervical LNM (p = 0.032) and poor disease-specific survival (p = 0.045).