乳腺癌中Fhit蛋白的低表达与转移的关系

背景与目的：脆性三联组氨酸（Fragile histidine triad,FHIT)基因为一种候选的肿瘤抑制基因,横跨大多数人类基因组的共同脆性位点FRA3B,FHIT基因的改变见于多种类型特别是上皮起源的人类类型肿瘤,并与已知的致癌物质作用有关,本研究目的为探讨乳腺癌中脆性三联组氨酸FHIT基因蛋白Fhit表达状况及其与临床病理指标的关系。方法：采用兔抗人Fhit蛋白抗体和枸椽酸－微波－链酶卵白素－过氧化物酶（Streptavidin-HRP,SP）免疫组化方法检测66例福尔马林固定,石蜡包埋的乳腺癌,其中6例为导管内癌,60例为浸润性导管癌的标本中Fhit表达状况并分析其与癌组织侵犯及淋巴结转移的关系。结果：癌组织Fhit表达强度较癌旁非癌乳腺组织低者为38例（57．6％）,其中22例为阴性（22．0％）,较癌旁非癌乳腺组织高者为18例（27．3％）,与癌旁非癌乳腺相等者为10例（15．2％）,伴局部或腋下淋巴结转移的乳腺浸润性导管癌Fhit蛋白表达低者阳性率为83．3％（20／24）,无淋巴结转移的浸润性导管癌为50．0％（18／36）,导管内癌为0／6,已伴淋巴结转移癌组83．3％（20／24）与未转移癌组42．9％（18／42）比较,差异有显著性（P＜0．01）,浸润性导管癌中已伴淋巴结转移癌组与未转移癌组比较,差异有非常显著性（P＜0．01）,结论：乳腺癌Fhit表达可能与癌组织侵犯及淋巴结转移相关,提示Fhit低表达可能对乳腺癌的演化和进展具有重要作用并可能成为一个新的预后指标。

Loss of fragile histidine triad expression and metastasis in breast cancer

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.