肝型脂肪酸结合蛋白和脂肪酸合成酶在乳腺浸润性导管癌的表达变化及其意义

目的:探讨肝型脂肪酸结合蛋白(L-FABP)和脂肪酸合成酶(FAS)与乳腺浸润性导管癌发生发展的关系.方法:用半定量逆转录聚合酶链反应、免疫组织化学和Western blot等方法检测L-FABP、 FAS和血管内皮生长因子(VEGF)在86例乳腺浸润性导管癌中的表达变化.结果:L-FABP和FAS主要分布于浸润性导管癌的腺泡和导管上皮细胞, L-FABP的mRNA和蛋白质的表达量在Ⅲ级浸润性导管癌的较Ⅰ、Ⅱ级明显上调(P<0.05).相反, FAS的表达量在Ⅲ级浸润性导管癌的较Ⅰ、Ⅱ级明显下调, 两者的表达无明显相关性(P>0.05).但是, L-FABP的表达与VEGF呈明显相关性.结论:在Ⅲ级浸润性导管癌, 随着FAS表达下调, L-FABP和VEGF的表达上调.     

膜联蛋白A2在乳腺癌及乳腺纤维腺瘤中的表达及意义

目的 研究膜联蛋白A2 (Annexin Ⅱ,ANX A2)在乳腺浸润性导管癌和乳腺纤维腺瘤中表达,以探讨其在乳腺癌发生发展中的作用.方法 分别使用免疫组织化学染色(SP)法和逆转录聚合酶链反应(RT-PCR)法检测乳腺浸润性导管癌和乳腺纤维腺瘤中ANX A2的蛋白表达水平和mRNA表达水平,并分析其在不同病理分级、临床分期及有无淋巴结转移的乳腺浸润性导管癌组织中的表达情况.结果 免疫组化结果显示乳腺浸润性导管癌组织中ANX A2表达高于乳腺纤维腺瘤(P＜0.05),RT-PCR结果也显示乳腺浸润性导管癌中ANX A2 mRNA的表达高于乳腺纤维腺瘤(P＜0.05).乳腺癌中ANX A2的表达与年龄、病理分级、临床分期和淋巴结转移呈正相关.结论 乳腺浸润性导管癌中annexinA2表达明显高于乳腺纤维腺瘤,annexinA2可能是乳腺癌的生物学标记物之一,其在乳腺癌的发生发展中可能扮演重要的角色.     

葡萄糖转运蛋白1在乳腺癌组织中表达的临床意义

目的 探讨葡萄糖转运蛋白1(glucose transporter 1,Glut-1)及其mRNA在正常乳腺组织、乳腺纤维腺病、乳腺纤维腺瘤和乳腺癌中的表达及其意义.方法 收集乳腺组织标本147例,其中乳腺浸润性导管癌92例、纤维腺瘤26例、腺病24例、正常乳腺组织5例,应用免疫组织化学EnVision法、Western blot以及RT-PCR分别定量检测不同病变组织中Glut-1蛋白及其mRNA表达水平.结果 在正常乳腺组织、乳腺腺病以及纤维腺瘤组织中难以检测到Glut-1阳性表达或仅呈轻微胞质着色.在乳腺癌组织中,Glut-1表达强度明显增高(P=0.0002),主要定位于瘤细胞膜,细胞质染色较淡.原发灶及转移灶中央的细胞Glut-1表达明显高于周边癌组织,转移灶Glut-1表达水平明显高于原发灶,浸润癌高于原位癌.Western blot定量分析结果显示,乳腺癌组织中Glut-1表达水平显著高于纤维腺瘤(P=0.001)和腺病(P=0.001),各病变组织间差异有统计学意义(P=0.0002).RT-PCR定量检测分析显示乳腺浸润性导管癌中Glut-1 mRNA的表达明显高于纤维腺瘤(P＜0.05)和腺病(P＜0.05),各病变组织间差异有统计学意义(P=0.0001).结论 乳腺癌组织中葡萄糖转运活性显著增高,Glut-1的表达水平与乳腺肿瘤的恶性程度、肿瘤细胞的浸润与转移密切相关;Glut-1高表达可作为细胞的恶性转化标志,并有望成为乳腺恶性肿瘤早期诊断、判断预后的一种新标记物及治疗的新靶点.     

COX-2、VEGF在乳腺癌组织中的表达及临床意义

目的探讨血管内皮生长因子(VEGF)和环氧化酶-2(COX-2)在乳腺癌组织中的表达及其与临床病理特征之间的关系。方法应用免疫组化S-P法检测不同乳腺组织中VEGF和COX-2的表达情况。结果VEGF、COX-2在乳腺导管癌组织中的表达明显上调,与其在正常乳腺组织、纤维腺瘤组织中的表达相比差异显著(P<0.01)。VEGF、COX-2在乳腺浸润性导管癌中的阳性表达率高于其在乳腺导管癌中的阳性表达率。两组中COX-2的表达有显著性差异(77.1%vs40%,P<0.05),VEGF的表达无显著性差异(80.0%vs70%,P>0.05)。VEGF在乳腺浸润性导管癌的阳性表达与其临床分期、淋巴结转移密切相关(P<0.05,P<0.01),与肿瘤大小无关(P>0.05)。COX-2在乳腺浸润性导管癌中的阳性表达与其临床分期、淋巴结转移及肿瘤大小均无关(P>0.05)。VEGF、COX-2在乳腺导管癌中的表达呈正相关(r=0.98,P<0.05)。结论VEGF、COX-2的高表达在乳腺癌的发生发展过程中起重要的作用,可作为重要的生物学标志。     

SASH1和p-ERK在乳腺浸润性导管癌中的表达及意义

目的观察SASH1和p-ERK在乳腺浸润性导管癌组织和正常乳腺组织中的表达,探讨其与乳腺浸润性导管癌生物学行为和预后的关系。方法应用免疫组织化学方法检测100例乳腺浸润性导管癌及40例正常乳腺组织中SASH1和p-ERK的表达,并结合肿瘤临床病理特征进行分析。Western blot方法检测20例新鲜乳腺浸润性导管癌组织及10例新鲜正常乳腺组织中SASH1和p-ERK的表达水平;实时荧光定量PCR方法检测两组SASH1mRNA和p-ERK mRNA的表达水平。结果 SASH1蛋白在乳腺癌组织表达率(31%)低于在正常乳腺组织表达率(80%),表达与组织学分级、淋巴结转移有关,而与肿瘤大小、TNM分期、发病年龄、激素受体表达无明显相关性。p-ERK蛋白在乳腺癌组织表达率(62%)高于正常乳腺组织(20%),表达与肿瘤大小、组织学分级呈正相关,与发病年龄、TNM分期、组织学分级、有无淋巴结转移、激素受体表达无明显相关。乳腺癌中SASH1的表达与p-ERK表达呈负相关(P0.005)。Western blot与实时PCR结果显示,与正常乳腺组织相比,SASH1蛋白与mRNA在乳腺癌组织中表达水平显著降低,p-ERK蛋白与mRNA在乳腺癌组织中表达水平显著升高(P0.01)。结论 SASH1的低表达和p-ERK的高表达与乳腺浸润性导管癌的发生发展密切相关。     

乳腺浸润性导管癌中Livin和MMP-7的表达及临床意义

目的检测凋亡抑制蛋白家族新成员Livin和基质金属蛋白酶-7(matrix metallo proteinase 7,MMP-7)在乳腺浸润性导管癌组织中的表达,探讨两者表达的相关性及其临床意义。方法采用免疫组化SP法检测Livin和MMP-7在乳腺浸润性导管癌和癌旁乳腺组织中的表达,并分析两者表达的相关性及其与乳腺浸润性导管癌患者临床病理特征的关系。进一步应用Western blot法检测乳腺浸润性导管癌及其相应的癌旁乳腺组织中Livin和MMP-7蛋白的表达水平。结果 Livin和MMP-7在乳腺浸润性导管癌和癌旁乳腺组织中的阳性率分别为65%vs 10%和73.3%vs 25%,且两者在乳腺浸润性导管癌组织中的阳性率均高于癌旁乳腺组织(P0.05)。统计学分析显示,Livin表达与乳腺浸润性导管癌患者的淋巴结转移和TNM分期具有正相关性(P0.05),MMP-7表达与乳腺浸润性导管癌的淋巴结转移、组织学分级均具有正相关性(P0.05)。Livin与MMP-7表达具有正相关性(r=0.322,P=0.007)。Western blot结果也表明,Livin与MMP-7蛋白在乳腺浸润性导管癌组织中的表达水平均高于癌旁乳腺组织。结论 Livin和MMP-7表达与乳腺浸润性导管癌的转移有关,两者可能具有协同作用促进乳腺浸润性导管癌的发展演进。     

乳腺癌和癌旁乳腺组织中Notch1基因mRNA及蛋白的表达

目的 检测Notch1基因mRNA及Notch1蛋白在人乳腺癌和癌旁乳腺组织中的表达,分析其临床病理学意义.方法 应用逆转录聚合酶链反应(RT-PCR)方法榆测60例乳腺浸润性导管癌和60例癌旁乳腺组织中Notch1基因mRNA,应用免疫组织化学SP法检测60例乳腺浸润性导管癌、30例导管原位癌及60例癌旁乳腺组织Notch1蛋白的表达,分析Notch1表达水平与乳腺癌临床病理特征的相关性.结果 Notch1基因mRNA在人乳腺浸润性导管癌及癌旁乳腺组织中均有表达.Notch1蛋白在癌旁乳腺组织和导管原位癌中的阳性牢分别为55%(33/60)、70%(21/30),二者差异无统计学意义(P>0.05),在乳腺浸润性导管癌中的阳性率为90%(54/60),明显高于癌旁乳腺组织和导管原位癌的阳性率(P<0.05).乳腺浸润性导管癌Notch1蛋白的高表达与肿瘤的淋巴结转移(P=0.006)、病理学分级(P=0.001)和TNM分期(P=0.022)均呈显著正相关.结论 乳腺浸润性导管癌存在Notch1蛋白的高表达.Notch1蛋白高表达与乳腺癌的恶变演进有关.Notch1基因的表达可能影响乳腺癌的发生、发展.     

乳腺浸润性导管癌中N-cadherin mRNA及蛋白的表达与预后分析

目的 探讨N-cadherin mRNA及蛋白在乳腺浸润性导管癌中的表达及其临床意义.方法 采用原位杂交技术和免疫组化SP法检测70例乳腺浸润性导管癌中N-cadherin mRNA及蛋白表达,以30例乳腺不典型导管增生为对照组.结果 乳腺浸润性导管癌中N-cadherin mRNA及蛋白阳性率分别为61.4%(43/70)、68.6%(48/70),乳腺不典型导管增生中N-cadherin mRNA及蛋白阳性率分别为3.3%(1/30)、6.7%(2/30),差异有统计学意义(P<0.01);N-cadherin mRNA及蛋白在乳腺浸润性导管癌中表达与淋巴结转移、TNM分期以及ER、PR表达有关,差异有统计学意义(P均<0.01);与患者年龄、肿瘤大小和组织学分级无关(P均>0.05);N-cadherin mRNA及蛋白在乳腺浸润性导管癌中表达呈正相关(rs=0.73,P<0.01);N-cadherin mRNA阳性患者生存率明显低于阴性患者,差异有统计学意义(P<0.01).结论 N-cadherin mRNA及蛋白在乳腺浸润性导管癌中的过表达提示其对乳腺癌发生、发展、浸润及转移起重要作用,并提示患者预后不良.     

miR-181通过Prox1促进人乳腺癌细胞系MCF-7的增殖并抑制凋亡

目的观察miR-181、同源异型盒转录因子(Prox-1)对乳腺癌细胞增殖及凋亡的影响,探讨miR-181及Prox-1在乳腺癌发生发展中的作用。方法荧光定量PCR检测癌旁乳腺组织、导管内癌组织、浸润性导管癌组织中miR-181的表达;pRFP-miR-181-inhibitor质粒转染乳腺癌细胞系MCF-7,荧光定量PCR和Western blot检测Prox1 mRNA及蛋白水平;EdU检测细胞增殖;TUNEL试剂盒检测细胞凋亡。结果与癌旁乳腺组织比较,导管内癌组织、浸润性导管癌组织内miR-181 mRNA表达上调(P0.01);抑制MCF-7细胞内的miR-181的表达,Prox1在蛋白水平明显上调(P0.05);MCF-7细胞的增殖能力减弱(P0.05)而凋亡增强(P0.05)。结论 miR-181可能通过抑制Prox1促进细胞的增殖、抑制细胞的凋亡,参与了乳腺癌的发生。     

锰超氧化物歧化酶在乳腺浸润性导管癌中的表达及临床意义

目的检测锰超氧化物歧化酶(manganese superoxide dismutase,MnSOD)在乳腺浸润性导管癌组织及癌旁正常组织中的表达,探讨MnSOD在肿瘤的发生及肿瘤侵袭过程中的作用。方法采用RT-PCR和Western blot法分别对20例乳腺浸润性导管癌组织样本和20例癌旁正常组织样本的MnSOD mRNA及蛋白表达进行检测,以β-actin作为定量参考物,比较其在乳腺癌组织和癌旁正常组织中的表达差异,并结合临床特征淋巴结转移和TNM分期,分析MnSOD在肿瘤不同阶段表达的差异。结果乳腺浸润性导管癌组织MnSOD mRNA的表达值为0.61±0.15,癌旁组织为1.24±0.14,两者比较差异具有统计学意义(P<0.01);MnSOD蛋白在癌组织中表达值为0.40±0.04,癌旁组织为0.75±0.06,两者比较差异具有统计学意义(P<0.01)。乳腺浸润性导管癌中淋巴结转移与非淋巴结转移MnSOD mRNA及蛋白表达无统计学意义(P>0.05)。TNM分期:Ⅰ期4例MnSOD mRNA表达值为0.45±0.15,Ⅱ期9例MnSOD mRNA表达值为0.44±0.15,Ⅲ期7例MnSOD mRNA表达值为0.36±0.07,Ⅱ期与Ⅲ期及Ⅰ期与Ⅲ期的比较差异均有统计学意义(P<0.05);Ⅰ期与Ⅱ期比较差异无统计学意义(P>0.05);Ⅰ～Ⅲ期MnSOD蛋白表达三者相互间比较差异均无统计学意义(P>0.05)。结论乳腺浸润性导管癌组织中Mn-SOD mRNA和蛋白表达明显下降,检测MnSOD的表达可作为临床诊治及判定乳腺浸润性导管癌预后的指标。     

BigH3 protein expression as a marker for breast cancer

The current hypothesis of tumorigenesis in humans suggests that cancer cells acquire their hallmarks of malignancy through the accumulation of advantageous gene activation and inactivation events over long periods of time. For breast cancer development, this multistep process may manifest itself as a sequence of pathologically defined stages. It is widely held that breast cancer originates at the premalignant stage of atypical ductal hyperplasia, progresses to the preinvasive stage of ductal carcinoma in situ, and culminates in the potentially lethal stage of invasive ductal carcinoma. Tumor grade has been a highly valuable prognostic factor for breast cancer, and high-grade ductal carcinoma in situ lesions are associated with poor clinical outcome. The aim of this work was to investigate the BigH3 protein expression changes associated with various stages of breast cancer progression in comparison to benign specimens using tissue microarray technology. Pathological characteristics of breast tissues ranged from benign lesions to breast cancers either of lobular or ductal carcinomas in origin, and included in situ ductal carcinomas, lobular carcinomas, infiltrating ductal carcinomas, carcinomas, scirrhous carcinomas, adenocarcinomas and infiltrating colloid carcinomas. BigH3 protein expression was analyzed by immunohistochemistry in 192 cases of breast tumors. Results indicated a decrease in BigH3 protein expression from benign tissues to in situ ductal carcinoma, lobular carcinoma, infiltrating ductal carcinomas, carcinomas, scirrhous carcinoma, adenocarcinomas to infiltrating colloid carcinomas. We observed that the benign tissue had a 23-fold increase in BigH3 protein expression compared to the infiltrating colloid carcinoma which was the most malignant tissue analyzed. In summary, these studies confirmed the suppressor effect of the BigH3 gene expressed as protein expression in those processes related to the progression of breast tumorigenesis. We conclude that this protein can be used as a marker for breast cancer progression.     

Expression of CD44s, CD44v6, and hyaluronan across the spectrum of normal-hyperplasia-carcinoma in breast.

BACKGROUND: The interaction between transmembrane receptors on epithelial tumor cells and the surrounding extracellular matrix molecules is important in tumor progression and metastasis. This interaction is best exemplified by the relationship of the receptor CD44 and the extracellular matrix component hyaluronan (HA). This study seeks to evaluate the expression and the correlation of CD44s, CD44v6, and HA in normal, hyperplastic, and malignant breast epithelium and stroma. MATERIALS AND METHODS: Archival paraffin-embedded tissue from cases of normal breast tissue (n=10), intraductal hyperplasia without atypia (n=13), ductal carcinoma in situ (DCIS) (n=24), stage I infiltrating ductal carcinoma (n=28), stage II infiltrating ductal carcinoma (n=31), and their corresponding positive lymph nodes were retrieved from the surgical pathology files. Tissue sections were evaluated for the expression of CD44s, CD44v6, and HA in the epithelial and stromal cells by immunohistochemistry. RESULTS: Ductal epithelial cells and myoepithelial cells expressed CD44s in all cases of normal and benign breast tissue. The expression of CD44s in breast epithelium progressively decreased with increasing deviation from normal histology: 83% in DCIS, 46% in stage I ductal carcinoma and 26% in stage II ductal carcinoma. The reverse trend was observed for CD44v6 in ductal epithelium: 0% in normal breast, 15% in intraductal hyperplasia, 100% in DCIS, 82% in stage I infiltrating ductal carcinoma, 94% in stage II carcinoma, and 100% of metastatic carcinoma in the lymph nodes. HA was noted exclusively in the stroma but not in the epithelial cells. HA was faintly expressed in the intralobular stroma of normal breast tissue, confined to a narrow faint band adjacent to intraductal hyperplasia and localized to a broad well-defined band around DCIS. Stromal HA staining was more diffuse and intense in infiltrating carcinomas and was particularly pronounced surrounding the metastatic deposits in lymph nodes. CONCLUSIONS: This study demonstrates decreased expression of CD44s accompanied by increased expression of CD44v6 and increased stromal HA in breast cancer. These findings suggest that CD44s, CD44v6, and HA play complementary roles in the development and progression of breast cancer.     

乳腺良、恶性病变组织中MMP-26蛋白的表达及其与ER的关系

目的检测基质金属蛋白酶-26(MMP-26)蛋白在人乳腺良、恶性病变组织中的表达,及其与部分临床指标的关系,分析MMP-26在肿瘤进展中的作用及临床意义,并探讨雌激素及其受体(ER)对MMP-26蛋白表达调节作用。方法应用免疫组化SP法,检测MMP-26蛋白在正常乳腺组织、乳腺增生症、原位癌和乳腺浸润性导管癌(IDC)中的表达,以及ER在IDC中的表达并进行评分,结果用INSTAT统计软件分析。结果6例正常乳腺组织和8例乳腺增生症中,分别有1例MMP-26呈弱阳性表达,阳性率分别为16.7%和12.5%。4例原位癌中MMP-26全部阳性表达。在67例IDC中,有41例MMP-26阳性表达,阳性率为61.2%。MMP-26的表达与发病年龄、肿瘤大小、病理学分级无关,而与淋巴结转移密切相关(P<0.05)。MMP-26蛋白在IDC的阳性表达与ER在癌组织中的表达呈明显的负相关(P<0.01)。结论MMP-26在肿瘤浸润和转移中发挥重要作用;MMP-26在IDC中的表达可能受雌激素及其受体的调节。     

Anomalous expression of P-cadherin in breast carcinoma. Correlation with E-cadherin expression and pathological features.

Previous studies on the cell-cell adhesion molecules P- and E-cadherin have shown that P-cadherin is not expressed in breast cancer. In contrast, the expression of E-cadherin is a normal event in these tumors, but a reduction in the levels of this molecule in neoplastic cells is associated with the histological type, high histological grade, greater tumor size, and metastasis. The expression pattern of P- and E-cadherin were immunohistochemically studied in tissue sections from normal breast tissue, benign breast lesions, and 57 infiltrating breast carcinomas. Cadherin expression was analyzed in parallel with pathological features and the immunohistochemical expression of estrogen and progesterone receptors in breast carcinomas. P-cadherin was detected in the myoepithelial cells and E-cadherin in luminal epithelial cells from normal breast and benign breast lesions. P-cadherin expression was detected in 9 of 45 cases (20%) of infiltrating ductal carcinomas of no special type; none of the special histological types that were analyzed (7 infiltrating lobular carcinomas, 3 colloid carcinomas, and 2 infiltrating papillary carcinomas) expressed P-cadherin. In infiltrating ductal carcinomas, P-cadherin expression correlated significantly with a reduction in E-cadherin expression, histological grade (all cases were grade III tumors), and hormone receptor content (8 of 9 cases were estrogen and progesterone receptor negative). Although E-cadherin was not found in the 7 infiltrating lobular carcinomas, it was present in the remaining histological types and was preserved in 15 infiltrating ductal and 3 colloid and 2 papillary carcinomas and was reduced in 30 infiltrating ductal carcinomas. In addition, a reduction in E-cadherin expression was significantly associated with high histological grade and a lack of steroid hormone receptors in infiltrating ductal carcinomas. No apparent relationship was found between P- and E-cadherin expression and tumor size and axillary lymph node metastasis. The distinct patterns of P- and E-cadherin expression observed in this study strongly suggest a differential role for these cadherins in human breast carcinogenesis.     

乳腺浸润性导管癌患者联合检测CA27-29和CA15-3的临床分析

目的探讨联合检测CA27-29与CA15-3水平对乳腺浸润性导管癌早期诊断的价值。方法采用IRMA和CMIA法检测乳腺浸润性导管癌组患者41例、乳腺良性疾病组33例和对照组35名,血清CA27-29与CA15-3水平。结果乳腺浸润性导管癌组血清CA27-29与CA15-3水平明显高于乳腺良性疾病组和对照组,差异有统计学意义（P〈0.05）;CA27-29与CA15-3的阳性率分别为65.9%和56.1%,这两项联合检测阳性率为80.5%,提示CA27-29异常表达与乳腺浸润性导管癌的发生密切相关。结论 CA27-29可以作为乳腺浸润性导管癌的肿瘤标志物之一,联合检测有助于乳腺浸润性导管癌的早期诊断。     

Expression of PC-cell-derived growth factor in benign and malignant human breast epithelium

PC-cell-derived growth factor (PCDGF, progranulin) is a novel autocrine growth factor that is overexpressed in human breast cancer cell lines. We have examined immunohistochemical PCDGF expression in 206 paraffin-embedded human breast lesions and investigated its association with clinicopathological variables. PCDGF staining was observed in breast carcinoma, whereas it was almost always negative in benign breast epithelium. PCDGF expression was more common in invasive ductal carcinoma (80% cases positive) than in invasive lobular carcinoma (53% positive). PCDGF staining was almost never observed in lobular carcinoma in situ. Ductal carcinoma in situ expressed PCDGF in 66% of the cases, and this expression correlated strongly with nuclear grade. Similar correlation was observed between PCDGF expression and histologic grade of invasive ductal carcinoma. Average Ki-67 index of PCDGF-negative/weakly positive invasive carcinomas (30.3) was significantly lower than that of strongly PCDGF-positive tumors (48.8, P=0.01). A larger percentage of tumors that expressed PCDGF with a staining intensity of 2+ or 3+ were p53 positive (44%) than were PCDGF-negative tumors (25%), P=0.02. PCDGF expression was independent of c-erbB-2 overexpression and of ER and PR status. Our study provides the first evidence of high incidence of PCDGF expression in human breast cancer in which it correlates with clinicopathological variables such as tumor grade, proliferation index, and p53 expression. These characteristics, as well as the virtual absence of expression in benign breast tissue, suggest an important role of PCDGF in breast cancer pathogenesis and make it a potential novel target for the treatment of breast cancer.     

乳腺浸润性导管癌连接蛋白43和上皮性钙黏蛋白相关性研究

目的探讨乳腺浸润性导管癌组织中间隙连接蛋白43(Cx43)及上皮性钙黏蛋白(E-cad)表达中的相关性。方法采用Elivision免疫组织化学法对89例乳腺侵润性导管癌组织及48例分区组织的Cx43与E-cad检测。结果乳腺浸润性导管癌的肿瘤区、交界区和远癌区的Cx43和E-cad蛋白表达具有较好的一致性(γ=0.460,P0.01);在肿瘤区两者同时为阴性表达时,淋巴结转移率最高。结论 Cx43和E-cad在乳腺浸润性导管癌发生和发展过程中具有一定的协同作用,与其发生浸润转移有关。     

Expression of heart-type fatty acid-binding protein in human gastric carcinoma and its association with tumor aggressiveness, metastasis and poor prognosis.

OBJECTIVE: Fatty acid-binding proteins (FABPs) are involved in lipid metabolism by intracellular transport of long-chain fatty acids. Heart-type (H-) FABP has been reported to inhibit cell growth and induce cell differentiation, but to our knowledge the significance of H-FABP expression in human gastric carcinoma has not been elucidated. The aim of the current study was to examine the expression of H-FABP and its relation to clinicopathologic parameters and fatty acid synthase (FAS) status of gastric carcinoma, since gastric cancer shows increased expression of FAS. METHODS: Immunohistochemistry with anti-H-FABP antibody was performed in 669 gastric carcinomas and 60 tubular adenomas of the stomach. H-FABP-positive and H-FABP-negative carcinomas were analyzed for their clinicopathologic characteristics and FAS status. RESULTS: None of the adenomas expressed H-FABP, whereas 127 of 669 carcinomas (19.0%) were positive for the protein. H-FABP positivity was associated with the depth of invasion (p <0.0001), vascular invasion (p <0.0001), lymph node metastasis (p <0.0001), hepatic metastasis (p=0.0011), stage of the carcinoma (p <0.0001) and FAS status of the carcinoma (p=0.0476). A higher survival rate was noted in H-FABP-negative cases compared with H-FABP-positive cases (p=0.0004). CONCLUSIONS: A subset of human gastric carcinoma expresses H-FABP and its expression is associated with FAS status, disease progression, tumor aggressiveness and poor patient survival.