nm23-H1、p53、PCNA表达与大肠癌浸润转移的关系

目的：研究大肠癌中ｎｍ２３－Ｈ１、ｐ５３、ＰＣＮＡ的表达与浸润转移的关系。方法：应用ＬＳＡＢ免疫组织化学方法检测７４例大肠癌中ｎｍ２３－Ｈ１、ｐ５３、ＰＣＮＡ和Ⅳ型原的表达。结果：大肠癌中ｎｍ２３－Ｈ１、ｐ５３和ＰＣＮＡ的阳性率分别为７１．６％、５２．７％和８１．１％。大肠癌中ｎｍ２３－Ｈ１低表达与淋巴结转移有关（Ｐ＜０．０２５），ｎｍ２３－Ｈ１的表达在Ⅳ型胶原表达不同的肠癌中无明显差异（Ｐ＞０．０５）；ｐ５３和ＰＣＮＡ过表达与浸润程度和淋巴结转移有关（Ｐ＜０．０５），ｐ５３和ＰＣＮＡ的表达在Ⅳ型胶原表达不同的肠癌中有非常显著的差异（Ｐ＜０．００５）；大肠癌中ｐ５３过表达与ｎｍ２３－Ｈ１低表达有关（Ｐ＜０．０１）。结论：实验结果揭示ｐ５３基因突变对于ｎｍ２３－Ｈ１基因的失活有一定影响，其作用机制有待深入研究。ｎｍ２３－Ｈ１低表达可能仅在大肠癌转移过程中发挥作用，ｐ５３过表达可在大肠癌浸润转移过程及细胞增殖中起重要作用。     

食管癌中Cath-D、nm23-H1蛋白的表达及其临床病理意义

目的：探讨组织蛋白酶Ｄ（Ｃａｔｈ－Ｄ）、肿瘤转移抑制基因表达蛋白（ｎｍ２３－Ｈ１）的表达与食管癌临床病理特点及预后的关系。方法：应用免疫组织化学Ｓ－Ｐ法，以兔抗Ｃａｔｈ－Ｄ、鼠抗ｎｍ２３－Ｈ１抗体标记６０例食管癌和５例正常的食管粘膜。观察不同分化程度和组织类型食管癌的表达情况，并比较其阳性率。结果：癌组织Ｃａｔｈ－Ｄ阳性３６例（６０．０％），ｎｍ２３－Ｈ１阳性３５例（５８．３％）。Ｃａｔｈ－Ｄ的表达与癌组织分化程度、浸润深度、淋巴结转移和预后均无关（Ｐ＞０．０５）；而ｎｍ２３－Ｈ１蛋白的表达则与癌组织分化程度及淋巴结转移有关（Ｐ＜０．０５，Ｐ＜０．０１），与癌组织浸润深度和预后无关（Ｐ＞０．０５）。结论：ｎｍ２３－Ｈ１可作为一种食管癌淋巴结转移的重要生物学标记物，但Ｃａｔｈ－Ｄ、ｎｍ２３－Ｈ１与预后的关系仍需进一步研究。     

甲状腺乳头状腺癌中EGFR、nm23-H1和p53蛋白的表达

目的：探讨 Ｅ Ｇ Ｆ Ｒ、ｎｍ２３ Ｈ１ 及ｐ５３ 蛋白在甲状腺乳头状腺癌中的表达及其与淋巴结转移的关系。方法：应用免疫组化 Ａ Ｂ Ｃ 法检测３６ 例有颈淋巴结转移的甲状腺乳头状腺癌的原发灶与转移灶和４０ 例无转移的甲状腺乳头状腺癌中 Ｅ Ｇ Ｆ Ｒ、ｎｍ２３ Ｈ１ 及ｐ５３ 蛋白的表达。结果：７６ 例甲状腺乳头状腺癌的 Ｅ Ｇ Ｆ Ｒ、ｎｍ２３ Ｈ１ 及ｐ５３ 蛋白的阳性表达率分别为５５３ ％ 、６０５ ％ 和１１８ ％ ;但有转移的甲状腺乳头状腺癌的 Ｅ Ｇ Ｆ Ｒ 阳性表达率高于无转移者（ Ｐ＜ ００５） ,且转移灶的 Ｅ Ｇ Ｆ Ｒ 阳性率明显高于其原发灶（ Ｐ＜ ００５） ;有转移的甲状腺乳头状腺癌的ｎ ｍ２３ Ｈ１ 阳性率低于无转移癌者（ Ｐ＜ ００１） ;甲状腺乳头状腺癌中 Ｅ Ｇ Ｆ Ｒ 的阳性表达与ｎ ｍ２３ Ｈ１ 的表达有负相关（ Ｐ＜ ００１） 。结论：甲状腺乳头状腺癌 Ｅ Ｇ Ｆ Ｒ 的过表达,ｎｍ２３ Ｈ１ 的低表达,二者表达的失平衡是其易于淋巴结转移的原因之一, Ｅ Ｇ Ｆ Ｒ,ｎｍ２３ Ｈ１ 联用可作为甲状腺乳头状腺癌淋巴结转移的评价指标。     

甲状腺乳头腺瘤中EGFR,nm—23—H1和p53蛋白的表达

目的：探讨ＥＧＦＲ、ｎｍ２３－Ｈ１及ｐ５３蛋白在甲状腺乳头状腺癌中的表达及其与淋巴结转移的关系。方法：应用免疫组化ＡＢＣ法检测３６例有颈淋巴结转移的甲状腺乳头状腺瘤的原发灶与转移灶和４０例无转移的甲状腺乳头状腺癌中ＥＧＦＲ、ｎｍ２３－Ｈ１和ｐ５３蛋白的表达。结果：７６例甲状腺乳头状腺癌的ＥＧＦＲ、ｎｍ２３－Ｈ１及ｐ５３蛋白的阳性表达率分别为５５．３％、６０．５％和１１．８％；但有转移的甲状腺乳头状     

乳腺癌p糖蛋白和nm23蛋白免疫组化研究

目的：按摩乳腺癌患者的ｐ糖蛋白表达与生存率、ｎｍ２３抑制癌转移基因与淋巴结转移之间的关系。方法：应用免疫组化Ｓ－Ｐ法，观察随访１０年以上的乳腺癌组织中ｐ糖蛋白和ｎｍ２３蛋白的表达。结果：ｐ糖蛋白和ｎｍ２３的阳性表达率分别为３６．５０％和９５．１２％。ｐ糖蛋白的阳性表达率仅与乳腺癌患者生存率有关（Ｐ〈０．０１），１０年以上较低，而与乳腺癌组织学分型，组织学分级，临床分期、淋巴结转移等无明显相关（Ｐ〉     

食管癌中Cath—D,nm23—H1蛋白的表达及其临床…

目的：探讨组织蛋白酶Ｄ（Ｃａｔｈ－Ｄ）、肿瘤转移抑制基因表达蛋白（ｎｍ２３－Ｈ１）的表达与食管癌临床病理特点及预后的关系。方法：应用免疫组织化学Ｓ－Ｐ法，以兔抗Ｃａｔｈ－Ｄ、鼠抗ｎｍ２３－Ｈ１体标记６０例食管癌和５例正常的食管粘膜，观察不同分化程度和组织类型食管癌的表达情况，并比较其阳性率。结果：癌组织Ｃａｔｈ－Ｄ阳性３６例（６０．０％），ｎｍ２３－Ｈ１阳性３５例（５８．３％）。Ｃａｔｈ－Ｄ的表达     

4种癌基因mRNA在胃癌组织中的表达及意义

应用原位分子杂交（ＩＳＨ）技术，检测８８例胃癌组织中Ｋ－ｒａｓ、Ｈ－ｒａｓ、Ｃ－ｍｙｃ和肿瘤转移抑制基因ｎｍ２３（Ｈ１）ｍＲＮＡ．其阳性结果分别为７８．４％、７０％、５８％和３８．６％，胃癌癌旁移行区正常粘膜和正常胃粘膜上皮的阳性率分别为１８．２％、１７％、１９．３％、２１．６％和０、０、０、３／５，与肿瘤区相比较，除ｎｍ２３外差异均非常显著（Ｐ＜０．０１）。Ｋ－ｒａｓ、Ｈ－ｒａｓｍＲＮＡ表达在在细胞膜内侧，Ｃ－ｍｙｃｍＲＮＡ主要表达在细胞核内，ｎｍ２３－Ｈ１ｍＲＮＡ表达在胞浆内。４种癌基因表达与组织学类型无关，ｎｍ２３－Ｈ１的表达与胃癌病人有无淋巴结转移有关（Ｐ＜０．０１）。     

肝细胞癌nm23—H1蛋白表达的研究

应用免疫组化检测８８例肝细胞癌中ｎｍ２３－Ｈ１蛋白的表达，癌旁肝组织强阳性表达，５１例肝癌组织阳性表达（５８％），阳性产物主要定位于肿瘤细胞胞浆。ｎｍ２３－Ｈ１蛋白表达与ＨＣＣ肿瘤体积，组织分型及Ｅ ｄｍｏｎｄｓｏｎ分级无关，而与肝内或肝外转移显著负相关，结果表明ｎｍ２３－Ｈ１在抑制ＨＣＣ肝内或肝外转移起着重要作用，有可能成为评价ＨＣＣ病人预凰的一项新指标。     

幽门螺杆菌与胃癌nm23,c—erbB2基因表达及术后再发癌的关系

目的：探讨胃癌组织幽门螺杆菌（Ｈｐ） 感染和ｎｍ２３ 、ｃｅｒＢ２ 表达及胃癌根治术后再发癌之间的关系。方法：用ＷａｒｒｔｈｉｎＳｔａｒｒｙ 方法检测胃组织幽门螺杆菌感染，采用免疫组化ＳＰ法检测６４ 例胃癌组织ｎｍ２３、ｃｅｒＢ２ 表达，并结合内镜及随访资料进行分析。结果：胃癌Ｈｐ 感染率、ｎｍ２３ 低表达率及ｃｅｒＢ２ 阳性率，在淋巴结转移组及术后３ 年内有再发癌组明显增高。而且ｎｍ２３ 低表达与肿瘤浸润程度有关，浸及浆膜及周围脏器组ｎｍ２３ 低表达率为７８－６％ ，浸及粘及粘膜下者为４０－０％ （Ｐ＜ ０ ．０５） 。Ｈｐ 感染者ｃｅｒＢ２ 阳性率、ｎｍ２３ 低表达率明显高于Ｈｐ 阴性组。结论：Ｈｐ 在胃癌发生、发展过程中起着重要作用。它可能通过影响癌基因蛋白的表在起促癌作用。胃癌ｎｍ２３ 低表达和ｃｅｒＢ２ 阳性表达者具有较强的浸润转移能力，且术后易发生再发癌，二者的表达变化对判断胃癌术后再发癌的发生及预后有重要意义。     

转移抑制基因nm23/NDPK与肺癌生物学行为的相关性研究

目的：研究转移抑制基因ｎｍ２３ 表达产物二磷酸核苷激酶（ＮＤＰＫ）在人肺癌中的表达及意义。方法：应用免疫组化ＳＰ法，检测不同病理分级及淋巴结有无转移肺癌组织中ｎｍ２３／ＮＤＰＫ 的表达。结果：８８ 例肺癌ｎｍ２３／ＮＤＰＫ 阳性表达率为８１－８２％ （７２／８８），其中呈高表达率３６－３６ ％（３２／８８） 。高分化肺癌高表达率７１－４３％ （１０／１４），中分化肺癌高表达率４１－３ ％（１９／４６） ，低分化肺癌高表达率１０－７２ ％ （３／２８） 。各组间有显著差异（ Ｐ＜ ０－０５）。而与肺癌有无肺门淋巴结转移无关（ Ｐ＞ ０－０５）。结论：ｎｍ２３／ＮＤＰＫ 的表达与肺癌的分化程度呈负相关，可作为预测肿瘤转移潜能及预后的指标之一。     

乳腺癌组织中uPA、uPAR及nm23-H1的表达

目的　观察乳腺癌组织中uPA、uPAR、nm2 3 H1的表达并探讨与腋窝淋巴结转移的关系。方法　用免疫组化EnVi sion两步法检测 6 9例乳腺癌组织中uPA、uPAR和nm2 3 H1表达的分布情况 ,观察其与肿瘤的分化程度以及与腋窝淋巴结转移的关系。结果　 (1)uPA阳性表达定位于癌细胞胞质 ;uPAR和nm2 3 H1阳性表达定位于癌细胞胞膜及胞质 ,多数癌旁乳腺上皮细胞呈nm2 3 H1阳性表达 ;高分化乳腺癌 (Ⅰ级 )uPA和uPAR表达阳性率 (30 0 %和 2 5 0 %)低于中低分化乳腺癌 (Ⅱ、Ⅲ级 ) (分别为 6 8 1%、72 7%和 70 0 %、74 1%) (P <0 0 5 ) ;nm2 3 H1表达阳性率在乳腺癌组织不同分化程度间差异无显著性 (P >0 0 5 ) ;(2 )腋窝淋巴结有转移者uPA和uPAR的表达阳性率 (73 2 %和 75 6 %)高于无淋巴结转移者 (35 7%和35 7%) (P <0 0 5 ) ;有腋窝淋巴结转移者nm2 3 H1的表达阳性率 (2 4 4 %)显著低于无淋巴结转移者 (5 0 0 %) (P <0 0 5 ) ;uPA、uPAR和nm2 3 H1的表达与淋巴结转移的个数均无关 ;(3)uPA阳性表达的癌组织其nm2 3 H1表达阳性率 (15 0 %)低于uPA阴性表达的癌组织 (6 2 1%) (P <0 0 5 )。结论　uPA和uPAR的高表达与乳腺癌腋窝淋巴结转移密切相关 ;uPA、uPAR和nm2 3 H1可以作为乳腺癌侵袭与淋巴结转移的     

nm23-H1 suppresses invasion of oral squamous cell carcinoma-derived cell lines without modifying matrix metalloproteinase-2 and matrix metalloproteinase-9 expression

nm23-H1 is a candidate gene for the suppression of cancer metastasis. Several studies on human breast, hepatocellular, gastric, ovarian, and colon carcinomas and melanomas have shown that reduced nm23-H1 expression was closely related to metastatic progression with poor prognosis. However, the biochemical mechanism by which nm23-H1 suppresses the metastasis has yet to be elucidated. In this study, we analyzed the correlation between nm23 expression, cell motility, and the invasive abilities of six different oral squamous cell carcinoma cell lines (HSC2, HSC3, HSC4, KB, OSC19, and OSC20). Reduced mRNA/protein expression of the nm23-H1 was observed in three cell lines (HSC2, HSC3, and HSC4). These cell lines exhibited increased cell motility and an invasive character on organotypic raft culture. On the other hand, the cell lines (KB, OSC19, and OSC20) that showed a higher expression of nm23-H1 exhibited a threefold to fivefold reduced motility and also reflected fewer invasions compared to the former three cell lines. Because the HSC3 cells demonstrated the lowest nm23-H1 expression with the highest cell motility and invasive character, we established nm23-H1-transfected HSC3 cell lines to investigate whether exogenous nm23-H1 protein could inhibit cell migration and invasive activity. These transfectants showed a significant reduction in cell motility with exogenous nm23-H1 in a dose-dependent manner, and exhibited a noninvasive character. An immunofluorescence study demonstrated a distinct stress-fiber distribution at peripheral region of these transfectants. However, no significant difference of matrix metalloproteinase (MMP)-2 and MMP-9 expression was observed between mock transfectant and nm23-H1-transfected cells. These findings suggest that nm23-H1 inhibits the invasive activity of oral squamous cell carcinoma by suppression of cell motility without altering the MMP-2 and MMP-9 status.     

甲状腺滤泡癌和乳头状癌细胞黏附分子与转移抑制基因nm23-H1蛋白表达的关系

目的 探讨黏附分子CD44、上皮性钙黏附蛋白（E-cad )和转移抑制基因nm23-H1与甲状腺滤泡源性癌分化、浸润转移的关系。方法 采用免疫组织化学SP法和EnVision法检测42例滤泡癌和54例乳头状癌中CD44、E-cad和nm23-h1的表达。结果 CD44主要表达于癌细胞及浸润淋巴细胞膜,低分化滤泡癌和有转移乳头状癌CD44表达分别高于高分化滤泡癌和无转移乳头状癌,E-cad阳性物质和nm23-H1阳性率高于滤泡癌,转移癌的阳性率和表达强度低于原发灶。甲状腺滤泡原性癌CD44检测阳性率高于E-cad和nm23-H1。在滤泡癌中E-cad与nm23-H1的表达之间呈正相关关系,而在乳头状癌中呈正相关趋势。CD44与E-cad的表达、CD44与nm23-H1的表达之间在滤泡癌和乳头状癌均呈负相关趋势。结论 综合检测CD44、E-cad和nm23对甲状腺滤泡源性癌的诊断、预后评估具有一定参考价值。     

乳腺癌微血管数与转移和预后的关系

目的探讨浸润性乳腺癌中微血管数（ＭＶＱ）与转移、预后的关系,ＭＶＱ与增殖细胞核抗原（ＰＣＮＡ）、ｃ－ｅｒｂＢ－２、ｎｍ２３－Ｈ１、组织蛋白酶Ｄ的关系。方法应用免疫组织化学ＬＳＡＢ法检测浸润性乳腺癌中ＭＶＱ与ＰＣＮＡ、ｃ－ｅｒｂＢ－２、ｎｍ２３－Ｈ１、组织蛋白酶Ｄ的表达。结果ＭＶＱ在７６例浸润性乳腺癌中的均数是５７．８２±２２．２２。ＭＶＱ与淋巴结转移、ｃ－ｅｒｂＢ－２、组织蛋白酶Ｄ（癌细胞）的表达无关;ＭＶＱ与远处转移（１０年内）、ＰＣＮＡ、组织蛋白酶Ｄ（间质细胞）表达呈正相关（Ｐ值均小于０．０１）;而与ｎｍ２３－Ｈ１、５年生存期呈负相关（Ｐ＜０．０１）。结论浸润性乳腺癌中ＭＶＱ与肿瘤的远处转移和生存期关系密切,可以作为一项独立的预后指标。     

散发性胆囊癌nm23-H1基因遗传不稳定性与错配修复基因hMLH1和hMSH2蛋白表达的研究

目的： 研究人类17号染色体D17S396位点微卫星不稳定性和杂合性缺失，对nm23-H1蛋白表达的影响，同时检测错配修复基因hMLH1和hMSH2蛋白的表达，为揭示nm23-H1基因、hMLH1和hMSH2基因与肿瘤发生和转移机制提供实验依据。方法: 采用石蜡包埋组织抽提DNA、PCR-SSCP、常规银染、Envision免疫组织化学等方法，对50例胆囊癌及其相应的正常组织，进行D17S396位点MSI、LOH的检测和nm23-H1、hMLH1和hMSH2蛋白表达研究。结果: ①原发性胆囊癌D17S396位点遗传不稳定发生率为42.55%，LOH的发生率与肿瘤组织分化程度差异显著（P <0.05）；在肝脏侵润和淋巴转移组高于无肝脏侵润和无淋巴转移组(P <0.01)，在NevinⅣ+Ⅴ期高于Ⅰ+Ⅱ+Ⅲ期(P <0.01)；而MSI发生率则相反；②nm23-H1蛋白阳性率为46.81%，在淋巴转移组低于无淋巴转移组(P <0.01)；NevinⅣ+Ⅴ期低于Ⅰ+Ⅱ+Ⅲ期(P <0.05)；③hMLH1和hMSH2蛋白阳性率分别为51.06%和42.55%，hMLH1蛋白表达在有无淋巴转移组和Nevin分期有显著差异(P <0.01)，肝脏侵润组低于无肝脏侵润组(P <0.05)；④MSI阳性组中hMLH1蛋白阳性率显著高于MSI阴性组(P <0.05)。LOH阳性组中nm23-H1和hMSH2蛋白阳性率显著低于LOH阴性组（P <0.05）；⑤hMSH2蛋白阳性组中nm23-H1蛋白表达明显高于hMSH2蛋白阴性组（P<0.05）。结论:nm23-H1基因的遗传不稳定性可能是胆囊癌发生、发展的一个重要分子机制。nm23-H1基因的MSI和LOH，通过相互独立的途径调控胆囊癌的发生和转移。hMLH1/hMSH2表达异常可能是胆囊癌的早期分子事件。提高胆囊癌局部nm23-H1、hMLH1和hMSH2蛋白的表达，可减缓肿瘤的侵润转移并提高预后率。     

Expression of the nm23 homologues nm23-H4, nm23-H6, and nm23-H7 in human gastric and colon cancer

Eight members of the nm23-gene family have been described. The involvement of nm23-H1 and nm23-H2 in tumour progression and metastasis, as well as in gene regulation and apoptosis, has been shown in numerous studies. Whether nm23-H4, -H6, and -H7 play a role in tumours is, however, largely unknown. This study describes data on the expression of these three nm23 homologues in human colon and gastric cancer by real-time RT-PCR and immunohistochemistry. Increased expression of these genes, most strikingly nm23-H4 and -H7, was observed in the majority of tumours analysed. No correlation with tumour stage according to the TNM classification was found. In contrast, by immunohistochemical analysis, nm23-H4 and -H6 overexpression correlated with the intestinal tumour type in gastric cancer tissues, whereas no increased immunoreactivity for the three nm23 proteins was noted in the diffuse type tumour specimens. These findings indicate that nm23-H6, and particularly nm23-H4 and -H7, may be involved in the development of colon and gastric carcinoma, the latter possibly in a type-specific manner. A contribution to tumour progression or metastasis could not, however, be proven. Elucidation of the specific mechanisms by which the nm23 homologues nm23-H4, -H6, and -H7 are involved in tumour development requires further studies.     

Understanding h-prune biology in the fight against cancer

The h-prune protein is a member of the DHH protein superfamily, and its overexpression in breast, colorectal and gastric cancers correlates with depth of invasion and degree of lymph-node metastasis. Taken together with the observation that h-prune is highly expressed in metastatic breast cancer, this suggests that h-prune can be used as a marker for the identification of subsets of cancer patients with highly aggressive tumours. H-prune possesses a phosphodiesterase (cAMP-PDE) activity, and inhibition of PDE activity with dipyridamole suppresses cell motility. H-prune interacts with nm23-H1, GSK-3β and gelsolin. Although a correlation between an h-prune PDE activity and cellular motility has been shown, GSK-3β does not affect the PDE activity of h-prune. Inhibition of the interactions between h-prune and GSK-3β and nm23-H1 additively suppresses the migration of colon cancer and breast cancer cells, thus suggesting that h-prune regulates cell motility by two different means of action: through its PDE activity and in its interactions with protein partners. Therefore, the identification of highly specific inhibitors of h-prune should be useful in the development of drugs to treat cancer metastasis.     

Increased activity of nm23-H1 gene in squamous cell carcinoma of the head and neck is associated with advanced disease and poor prognosis

The present study was undertaken to determine whether the nm23-H1 gene is expressed in squamous cell carcinoma of the head and neck (SCCHN) and whether the level of nm23-H1 protein or mRNA in cells vary as they progress to a more malignant phenotype. Of the 120 SCCHN studied 54 (45%) stained positively for nm23-H1 protein. Protein expression was significantly higher in more advanced stages of disease. Expression of nm23-H1 was significantly higher in cancer tissues than in normal, adjacent tissue, dysplasia, or carcinoma in situ. The nm23-H1 rate increased with progression of synchronous lesions from dysplasia to carcinoma in situ and finally to carcinoma (P<0.05). Northern blot analyses of tissues with various clinicopathological characteristics also revealed differences in nm23-H1 mRNA expression. When levels of nm23-H1 mRNA were compared to tumor stage, intensity of expression was found to be higher in stages 3 and 4 than stages 1 and 2 (P<0.01). Malignant tumors had a higher level of mRNA nm23-H1 expression than normal or premalignant tissues. The nm23-H1 negative patients survived significantly longer than nm23-H1 positive ones (P<0.05). To study the possible relationship between nm23-H1 gene expression and cell growth rate in tumor cells, the mRNA level in each tumor was compared to proliferative activity. The nm23-H1 gene expression levels were directly related to the [3H]thymidine labeling index in tumor cells (R=0.6681). Our results strongly indicate that the nm23-H1 gene is involved in progression of SCCHN. Together with results obtained on lung cancer, our observations suggest that increased expression of nm23-H1 in cancers of the upper aerodigestive tract may have different implications than elsewhere in the body.     

影响肝细胞癌生物学行为及预后的相关因子分析

目的探讨影响肝癌生物学行为及预后的重要因素和寻求肝癌基因治疗的有效靶点。方法运用免疫组化方法检测Ki67、nm23H1、cMet及MT1MMP蛋白在93例肝细胞癌组织中的表达水平,并判断其与肝癌细胞恶性生物学行为及患者预后的关系。结果Ki67、nm23H1、cMet及MT1MMP蛋白表达水平与肝癌患者预后均具有显著相关性(P均<0.01);nm23H1的表达与肿瘤远处转移之间呈负相关关系(P=0.041);cMet、MT1MMP的表达与肝癌瘤旁浸润及远处转移之间均呈正相关关系(P<0.05)。结论nm23H1基因的失活或突变,伴随cMet以及MT1MMP蛋白的异常表达可能是导致肝癌浸润、转移的关键因素。     

Squamous cell lung carcinomas: the role of nm23-H1 gene

 This analysis of 32 pairs of human squamous cell lung carcinomas and normal matched control DNA demonstrates that loss of heterozygosity (LOH) is infrequent at the nm23-H1 locus, affecting only 2 of the 18 informative cases. Both LOH cases were in the tumor stage IIIA. One tumor was of poor and the other of moderate histological grade. These and an additional 34 tumor samples were also analyzed immunohistochemically for the presence of nm23-H1 protein. Of the 66 cases tested for the presence of nm23-H1 protein 54 were negative. Eight samples exhibited up to 35% positive cells (with weak immunostaining intensity) and four between 35% and 70% (moderate immunostaining intensity); no sample showed more than 70% positive cells. Noncancerous lung parts contained no nm23-H1 protein. nm23-H1 expression was independent of TNM stage, grade, tumor size, and patient’s survival. Two samples with LOH were negative for nm23-H1 protein. We therefore conclude that neither loss of heterozygosity of the nm23-H1 gene nor the intensity of specific protein expression are related to squamous cell lung carcinoma development and progression. Received: 27 January 1997 / Accepted: 9 May 1997