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1.
Objective To evaluate the clinical diagnostic application and operative efficacy of the expression of NKG2D in peripheral blood CD+8 NKT cell and its ligand sMICA in patients with esophageal or cardiac carcinoma.Methods The peripheral blood NKG2D positive CD+8 NKT cell percentage was concomitantly determined by flow cytometry in 53 preoperative patients including 29 postoperative patients with esophageal or cardiac carcinoma and 30 healthy controls.The serum sMICA was determined by ELISA.Results The peripheral blood NKG2D positive CD+8 NKT cell percentage in patients was significantly lower than that in controls [(77.632±8.972) % vs (89.053±6.515) %] (t = -6.113,P <0.05); with stage Ⅱ,Ⅲ,Ⅳ,it decreased significantly in order (F = 99.251,P <0.01);with lymph node metastasis lower than that without lymph node metastasis (t = -10.384,P <0.01); squamous carcinoma was higher than adenocarcinoma (t =9.899,P <0.01); postoperative was significantly higher than preoperative (t =-4.319,P <0.01).The level of serum sMICA in patients was significantly higher than that in controls [(326.28±85.407) pg/ml vs (210.00±92.560) pg/ml](t =7.292,P <0.01); with stage Ⅱ,Ⅲ,Ⅳ,it increased significautly in order (F =63.355,P <0.01); with lymph node metastasis higher than that without lymph node metastasis (t =7.770,P <0.01); squamous carcinoma was lower than adenocarcinoma (t =-7.593,P<0.01); postoperative was significantly lower than preoperative (t =7.027,P <0.01).Serum sMICA could inhibit peripheral blood CD+8 NKT cell activation receptor NKG2D (F =142.773,P <0.05),determination coefficient R2 = 0.7368.Conclusion The level of peripheral blood CD+8NKT cell activation receptor NKG2D and serum sMICA in patients could be an assistant indicator for  相似文献   

2.
Objective To investigate the expression of E-cadherin in nasopharyngeal carcinoma ( NPC) and its relationship with cervical lymph node metastasis. Methods The expression of E-cadherin in 80 patients with NPC was detected by immunohistochemistry. Results Lower expression of E-cadherin was associated with advanced N-stage of the tumor ( P = 0. 018 ). There was no significant correlation between the expression of E-cadherin and lymph node size ( P = 0.435 ). The expression of E-cadherin was higher in patients with cervical lymph node metastasis limited to a single area than that distributing in some scattered areas (P = 0. 000). There was a trend that the expression of E-cadherin in the cases with the tumor and lymph nodes in the same side was higher (56. 5% ) than that in the patients with bilateral lymph node metastases (32. 6% ) , however, the difference was not significant (P =0. 059). The expression rates of E-cadherin in patients with lymph node metastasis in levels Ⅱ , Ⅲ and Ⅴa were higher than that in levels Ⅰ , Ⅳ, Vb and Ⅵ, but with a non-significant difference (P = 0.059). Conclusion The expression of E-cadherin has influence on the lymph node metastasis in nasopharyngeal carcinoma. E-cadherin expression is negatively correlated with the numbers of the lymph node metastases and the metastasis distance, i. e. a lower expression of E-cadherin leads to an advanced N-stage. The lymph node metastasis of nasopharyngeal cancer from above to below is more considerably influenced by E-cadherin expression than the metastasis towards contralateral lymph nodes.  相似文献   

3.
Objective To investigate the expression of E-cadherin in nasopharyngeal carcinoma ( NPC) and its relationship with cervical lymph node metastasis. Methods The expression of E-cadherin in 80 patients with NPC was detected by immunohistochemistry. Results Lower expression of E-cadherin was associated with advanced N-stage of the tumor ( P = 0. 018 ). There was no significant correlation between the expression of E-cadherin and lymph node size ( P = 0.435 ). The expression of E-cadherin was higher in patients with cervical lymph node metastasis limited to a single area than that distributing in some scattered areas (P = 0. 000). There was a trend that the expression of E-cadherin in the cases with the tumor and lymph nodes in the same side was higher (56. 5% ) than that in the patients with bilateral lymph node metastases (32. 6% ) , however, the difference was not significant (P =0. 059). The expression rates of E-cadherin in patients with lymph node metastasis in levels Ⅱ , Ⅲ and Ⅴa were higher than that in levels Ⅰ , Ⅳ, Vb and Ⅵ, but with a non-significant difference (P = 0.059). Conclusion The expression of E-cadherin has influence on the lymph node metastasis in nasopharyngeal carcinoma. E-cadherin expression is negatively correlated with the numbers of the lymph node metastases and the metastasis distance, i. e. a lower expression of E-cadherin leads to an advanced N-stage. The lymph node metastasis of nasopharyngeal cancer from above to below is more considerably influenced by E-cadherin expression than the metastasis towards contralateral lymph nodes.  相似文献   

4.
Objective: To evaluated Bromodeoxyuridine (BrdUrd)/DNA doubleparametric method in detection of gastric carcinoma and to analyze the relationships of cellular BrdUrd labeling indices(LI), G2/M-phase fraction(G2/MPE) and DNA content to the depth of invasion, lymphatic vessel invasion, lymphatic node metastasis, peritoneal dissemination and blood vessel invasion and prognosis.Methods: Fresh tumor samples from 60 cases were examined by BrdUrd/DNA doubleparametric flowcytometry. Propidium iodide(PI) was used as fluorescent probe for total cellular DNA and a monoclonal antibody against BrdUrd incorporated into DNA.Fluorescein-labeled goat anti-mouse antibody was used as second antibody. Results: The values of BrdUrd LI in patients with serosa invasion was significantly higher than those without serosa invasion (P<0.01); there was statistical significance in 5-year survival rate between the two groups (P<0.01). Both BrdUrd LI and G2/MPF values were significantly higher in patients with lymphatic vessel invasion than those without invasion (P<0.01); the patients with lymphatic vascular invasion carried a significantly poor prognosis (P<0.01). Both BrdUrd LI and G2/MPF values were significantly higher in patients with lymphatic node metastasis than those without metastasis (P<0.01),there was a statistical significance in 5 years survival between these 2 groups. The incidence of lymphatic node metastasis was significantly higher in aneuploid carcinoma (P<0.05), and the patients with aneuploid carried a significantly poor prognosis (P<0.05). Patients with peritoneal dissemination had a significantly worse prognosis (P<0.01). G2/MPF values were significantly higher in patients with blood vessel invasion than thosew ithout invasion (P<0.01). Conclusion: Cellular BrdUrd LI,G2/MPF and DNA content are related to depth of invasion,lymphatic vessel invasion, peritoneal dissemination, blood vessel invasion and prognosis of gastric carcinoma.  相似文献   

5.
Objective To study the expression of RhoB-mRNA,and periphery regions in human laryngeal carcinoma.Methods The expression of RhoB-mRNA were examined by RT-PCR method.Results It was noted that the expression of RhoB-mRNA was positively correlated well with the clinical stages.The expression of RhoB-mRNA in carcinoma with node metastasis group was significantly higher than that without node metastasis.The difference between the two groups was statistically significant(P<0.05).The expression of RhoB-mRNA in different types and stages of laryngeal carcinoma was significantly different(P<0.05).The expression of RhoB in laryngeal carcinoma negtive correlation with the stages of laryngeal carcinoma(r=0.557).Conclusion The expression of RhoB plays an inhibitive role in the growth,invasion and local node metastasis of human laryngeal carcinoma.RhoB promote the formation,invasion and lymph node metastasis as oncogenes.It may be valuable as predictors for lymph node metastasis and prognosis.  相似文献   

6.
Objective: To study the expressive characteristics of SKP2 protein in lung carcinoma and its implication for prognosis. Methods: The expression of SKP2 protein was detected in 89 non small cell lung carcinoma, 13 small cell lung carcinoma, 10 lung benign lesion tissues by Tissue Chip and Immunohistochemistry technology. Results: The positive rate of SKP2 protein staining was (23.52±13.57)% in non small cell lung carcinoma and (53.85±12.26)% in small cell lung carcinoma, which were significantly higher than (2.91±1.27)% in lung benign lesion tissues. It was highest in small cell lung carcinoma and lowest in lung benign lesion tissues, with a significant difference between them (P=0.000). The expressive level of SKP2 protein in lung carcinoma tissues was closely related to cell differentiation, lymph node metastasis and pathological types, but not to age, sex, smoking history, tumor site and size, and TNM staging. The survival analysis revealed that the 5-year survival rate of lung carcinoma patients was lower in SKP2 protein positive expression group than that in negative expression group (P1=0.003/0.002; r=-0.275, P2=0.005). Conclusion. The positive expression of SKP2 protein is higher in lung carcinoma than in lung benign lesion tissues, in particular, much higher in small cell lung carcinoma. In lung carcinoma, its expressive level was closely related to cell differentiation, lymph node metastasis and pathological types. Moreover, it may be an independent factor to prognosis of patients with lung carcinoma.  相似文献   

7.
Objective: To explore the effect of immune function on lymph node micrometastasis in esophageal cancer patients by the research on the correlation between immune function and micrometastasis. Methods: Ratios of T-lymphocyte subsets CD3+, CD4+, CD8+ and CD4+/CD8+ in peripheral blood were examined by flow cytometry, but no lymph node with metastatic cancer cells was observed in middle thoracic esophageal squamous carcinoma patients by routine pathological examination. The patients were divided into 2 groups with or without micrometastasis to detect micrometastasis by immunohistochemical method, and T-lymphocyte subsets levels were compared between the 2 groups. Results: CD3+ and CD4+ T-lymphocytes levels of the group with micrometastasis were significantly lower than those of the group without micrometastasis, while CD8+ level of the group with micrometastasis was significantly higher than that of the group without micrometastasis. Conclusion: T-lymphocyte subset is closely relative with micrometastasis, and prognosis of the patients with low CD3+ and CD4+ levels but high CD8+ T-lymphocytes is comparatively poor.  相似文献   

8.
9.
Objective To investigate the level of ERCC1 mRNA expression in non-small cell lung cancer and analyze the influencing factors of the survival of patients after operation. Methods The level of ERCC1 mRNA expression was quantified in sixty pairs of non-small cell lung cancer tissue and their matched normal lung tissues by real-time PCR assay. The survival of patients was analyzed by univariate Kaplan-Meier and Cox regression analysis. Results The level of ERCC1 mRNA expression in cancer tissues ( -7.85 ±3.86) was significantly higher than that in matched normal ones ( - 11. 19 ±5.03;t=3.973, P=0.000). Up-regulation of ERCC1 mRNA was found in 43 of 60 (71.7% ) lung cancer tissues compared with that in the matched normal lung tissues (17 of 60, 28.3% ). The univariate survival analysis by Kaplan-Meier method showed that the survival rate of patients with high ERCC1 mRNA expression was lower than that in the patients with low expression of ERCC1 mRNA (P=0.000). Patients with lymph node metastasis, smoking, cancer family history, or high pathological grade had significantly shorter survaival time than those without lymph node metastasis, smoking, cancer family history, or with low pathological grade. Cox regression survival analysis showed that the level of ERCC1 mRNA expression, lymph node metastasis, smoking, and pathological grade were significant independent factors affecting the survival rate. Conclusions Non-small cell lung cancer patients with up-regulated ERCC1 expression have a poor survival. The expression of ERCC1 mRNA, lymph node metastasis, pathological grade, cancer family history and smoking can be used as prognostic indicator of non-small cell lung cancer.  相似文献   

10.
马望  李雯  高明  李向楠 《中华肿瘤杂志》2010,33(12):371-374
Objective To investigate the level of ERCC1 mRNA expression in non-small cell lung cancer and analyze the influencing factors of the survival of patients after operation. Methods The level of ERCC1 mRNA expression was quantified in sixty pairs of non-small cell lung cancer tissue and their matched normal lung tissues by real-time PCR assay. The survival of patients was analyzed by univariate Kaplan-Meier and Cox regression analysis. Results The level of ERCC1 mRNA expression in cancer tissues ( -7.85 ±3.86) was significantly higher than that in matched normal ones ( - 11. 19 ±5.03;t=3.973, P=0.000). Up-regulation of ERCC1 mRNA was found in 43 of 60 (71.7% ) lung cancer tissues compared with that in the matched normal lung tissues (17 of 60, 28.3% ). The univariate survival analysis by Kaplan-Meier method showed that the survival rate of patients with high ERCC1 mRNA expression was lower than that in the patients with low expression of ERCC1 mRNA (P=0.000). Patients with lymph node metastasis, smoking, cancer family history, or high pathological grade had significantly shorter survaival time than those without lymph node metastasis, smoking, cancer family history, or with low pathological grade. Cox regression survival analysis showed that the level of ERCC1 mRNA expression, lymph node metastasis, smoking, and pathological grade were significant independent factors affecting the survival rate. Conclusions Non-small cell lung cancer patients with up-regulated ERCC1 expression have a poor survival. The expression of ERCC1 mRNA, lymph node metastasis, pathological grade, cancer family history and smoking can be used as prognostic indicator of non-small cell lung cancer.  相似文献   

11.
目的:分析正常乳腺组织和浸润性导管癌中SIAH2和Bcl-2的表达及临床意义,探讨其在乳腺癌发生发展中的作用及相关性.方法:采用免疫组织化学S-P法检测SIAH2和Bcl-2蛋白的表达,并分析二者的相关性及与临床病理因素的关系;采用Western Blot法检测SIAH2和Bcl-2蛋白的表达.结果:SIAH2与Bcl-2蛋白在乳腺癌癌变过程中的阳性表达率逐渐升高,并且二者表达与乳腺癌组织学分级、ER、PR相关.免疫组化结果表明SIAH2与Bcl-2蛋白在乳腺正常组织和浸润性导管癌中的阳性表达率分别为8.7%和17.4%,75%和72.5%.统计学结果显示在80例乳腺癌组织中,SIAH2与Bcl-2蛋白表达呈正相关(P<0.001,rs=0.485).Western blot结果表明SIAH2与Bcl-2蛋白在乳腺癌组织中表达高于癌旁乳腺组织,在乳腺癌细胞系MDA-MB-435S和MCF-7中表达高于乳腺正常上皮细胞系MCF-10A.结论:SIAH2与Bcl-2在乳腺癌发生发展中均存在异常,并且两者可能存在某种协调关系.  相似文献   

12.
目的 探讨癌基因Her-2和Cox-2在乳腺癌组织中的表达及其相关性.方法 应用免疫组化技术,检测40例人乳腺癌中Her-2和Cox-2蛋白的表达情况,分析其相互关系及与乳腺癌的临床病理特征间的联系.结果 40例乳腺癌组织中Her-2表达阳性率为35﹪(14/40),与肿瘤分期、淋巴结转移及阴性激素受体状态密切相关(P<0.05);Cox-2表达阳性率为47.5﹪(19/40),与肿瘤分期、组织学分级、阴性激素受体状态密切相关(P<0.05);二者表达与肿瘤大小无关,两者的表达存在显著的相关性(P<0.01).结论 Cox-2在乳腺癌中高水平表达且与Her-2密切相关,提示乳腺癌中Her-2和Cox-2存在相互调控机制共同促进肿瘤的发生和发展.  相似文献   

13.
背景与目的:细胞外基质的降解是肿瘤侵袭转移的重要步骤,基质金属蛋白酶(MMPs)是目前已知的唯一能降解胶原纤维的酶类,而基质金属蛋白酶-2(MMP-2)能特异地降解细胞外基质(ECM)的主要成分Ⅳ型胶原,为Ⅳ型胶原酶,它与肿瘤的侵袭转移有关。C—erbB-2是生长因子受体,又是Ⅰ型跨膜酪氨酸激酶受体家族的成员,它的表达水平与散发性结直肠癌的预后关系值得研究。本文就MMP-2和C—erbB-2在散发性结直肠癌原发及转移灶中的表达、相互关系及临床意义进行研究。方法:采用免疫组织化学EnVision法检测104例散发性结直肠癌原发及转移灶中C—erbB-2和MMP-2的表达情况,并分析其在侵袭转移过程中的作用。结果:MMP-2在转移灶中的阳性率(72.1%)显著高于原发灶中的阳性率(53.8%)(P〈0.05);C—erbB-2在转移灶中的阳性率(50.0%)高于原发灶中的阳性率(38.5%),但两者之间差异无显著性(P〉0.05);MMP-2和C—erbB-2在结直肠癌原发及转移灶中表达均具有相关性(P〈0.05),且呈正相关(0〈r〈1)。结论:MMP-2和C—erbB-2的表达增高与结直肠癌转移密切相关,MMP-2的分泌增加可能与C—erbB-2的过表达有关,可作为临床判断结直肠癌转移及预后等生物学行为的重要参考指标。  相似文献   

14.
刘霖 《现代肿瘤医学》2011,19(4):733-735
目的:探讨FHL-2和COX-2在胃癌组织中的表达及相关性。方法:采用ABC免疫组化染色法检测41例胃癌患者的胃黏膜组织中FHL-2蛋白和COX-2蛋白的表达情况。结果:在胃癌组织中FHL-2和COX-2的表达阳性率分别为85.4%和90.2%,均显著高于慢性胃炎组织(P<0.05)。FHL-2和COX-2在胃癌组织中表达具有相关性。结论:FHL-2和COX-2在胃癌组织中的表达具有一定的相关性。  相似文献   

15.
 目的 探讨转录因子AP02在乳腺癌中表达及其与c-erbB-2表达的相关性。方法 应用免疫组织化学染色技术(SP法)检测128例乳腺癌组织中AP02和c-erbB-2的表达。结果 c-erbB-2和AP02在128例浸润性导管癌中过表达率分别为30.46%(39/128)和34.38%(44/128)。对照组乳腺增生病与乳腺癌组织中AP02的过表达率有显著差异(X^2=6.91,P〈0.01)。乳腺癌中AP_2的过表达与患者年龄(χ2=2.3,P〉0.05)、肿块大小(χ2=2.58,P〉0.05)及淋巴结转移(χ2=0.32,P〉0.05)无关,而与肿瘤组织学分级有关。在组织学分级Ⅰ、Ⅱ、Ⅲ级肿瘤组织中AP-2(χ2=7.46,P〈0.05)的过表达均有显著差异,且随着组织学分级的增高,AP-2的过表达率也相应增加。128例乳腺癌中c-erbB-2和AP-2的过表达具有相关性(r=0.87,P〈0.01),且呈正相关关系(0〈r〈1)。结论 AP-2在乳腺癌组织中存在过表达,与c-erbB-2一样可作为判断预后或选择化疗用药的指标。  相似文献   

16.
目的:探讨人乳腺癌中Plexin-B 2 的表达,以及其与人表皮生长因子受体-2(Her-2)共表达与乳腺癌恶性行为的关系。方法:免疫组化SP法检测15例正常乳腺组织中Plexin-B 2 蛋白的表达,及112 例乳腺癌组织中Plexin-B 2 和Her-2 蛋白的表达。结果:Plexin-B 2 在癌细胞和正常乳腺组织小叶及导管上皮细胞中的阳性表达率分别为69.64% 和60.00% ,差异无统计学意义(P>0.05)。 Plexin-B 2 在乳腺癌组织癌周微脉管中的阳性表达率为44.64% ,而正常乳腺微脉管均为阴性。癌细胞和癌周微脉管中Plexin-B 2 的表达正相关(r=0.593,P=0.000),并且都与临床分期及淋巴结转移有关(P<0.05)。 Plexin-B 2、Her-2 共表达比Plex in-B 2 单阳性的肿瘤临床分期晚、淋巴结转移率高,差异有统计学意义(P<0.05)。 结论:Plexin-B 2 异常表达可能与乳腺癌的恶性进展有关,Plexin-B 2-Her- 2 共表达可能促使乳腺癌的侵袭转移。   相似文献   

17.
目的分析ABCG2和空泡型ATP酶(V—ATPase)在非小细胞肺癌(NSCLC)病理分类、TNM分期、病理分级中表达的差异性以及相关性。方法对92例NSCLC组织样本采用免疫组织化学EnVision法检测ABCG2和V—ATPase的表达。结果ABCG2、V—ATPase在腺癌和鳞癌中有表达,差异有统计学意义(P=0.003、P=0.000)。ABCG2在腺癌TNM分期中的表达差异有统计学意义(P=0.004),在鳞癌TNM分期中差异无统计学意义;在腺癌和鳞癌病理分级的表达差异有统计学意义(P=0.028、P=0.000)。V—ATPase在腺癌TNM分期、鳞癌病理分级间的表达差异有统计学意义(P=0.026、P=0.002),在鳞癌的TNM分期、腺癌病理分级组间的表达差异无统计学意义。在总体样本及腺癌、鳞癌中ABCG2和V—ATPase的表达有相关性。结论V—ATPase可能与ABCG2共同参与NSCLC的多药耐药机制。  相似文献   

18.
目的 探讨肝癌及癌旁组织中FMNL-2和MMP-2的蛋白表达及与临床病理特征的关系。方法采用免疫组织化学MaxvisionTM法检测100例肝癌及癌旁组织中FMNL-2和MMP-2的蛋白表达情况,应用图文分析软件Image-Pro Plus6.0测定FMNL-2和MMP-2的蛋白累积吸光度值(IOD),采用SPSS19.0软件统计分析。结果 肝癌及癌旁组织中FMNL-2蛋白IOD值分别为(90 748.36±46 276.91)和(39 075.46±24 763.12),MMP-2蛋白IOD值分别为(87 969.46±27 131.77)和(59 517.72±20 218.23),两组差异均有统计学意义(P<0.05);FMNL-2在伴与不伴肝硬化组中IOD值分别为(47 471.96±40 273.54)和(72 123.41±45 517.93)(P<0.05);MMP-2在HBsAg阳性或阴性组中IOD值分别为(77 668.34±27 682.79)和(64 585.83±26 173.62)(P<0.05),在有无转移组中IOD值分别为(63 854.73±21730.42)和(77 218.05±28 930.01)(P<0.05),差异有统计学意义;并且肝癌及癌旁组织中FMNL-2和MMP-2蛋白表达呈正相关(r=0.240,P=0.016)。结论 在肝癌发生、发展过程中存在FMNL-2和MMP-2蛋白异常表达,联合监测两者蛋白表达可能会有助于肝癌的诊断。  相似文献   

19.
MUC2、CDX2在大肠肿瘤中联合表达的意义   总被引:1,自引:0,他引:1  
  目的 探讨粘蛋白MUC2、CDX2在大肠腺癌中的分型及其与临床各个病理因素之间的关系。方法 应用免疫组织化学方法对30例大肠腺瘤、60例大肠腺癌及相应正常大肠黏膜30例进行粘蛋白MUC2、CDX2检测。结果 在大肠正常黏膜、腺瘤、腺癌中,MUC2阳性率分别为100%、93.3%、58.3%;CDX2为90.0%、76.7%、31.7%。根据MUC2和CDX2在大肠腺癌中的表达把大肠腺癌分为四型:MUC2+CDX2+、MUC2+CDX2-、MUC2- CDX2+、MUC2- CDX2-,MUC2+CDX2+型与分化程度、浸润深度、Dukes分期以及生存期相关;MUC2+CDX2-型与淋巴结转移相关;MUC2- CDX2+与临床病理因素不相关;MUC2- CDX2-型与分化程度、浸润深度、淋巴结转移、Dukes分期以及生存期具有明显的相关性。结论 MUC2、CDX2的下调表达可能参与了大肠腺癌的发生,MUC2+CDX2+、MUC2- CDX2-型大肠腺癌与肿瘤的发生、发展、浸润及转移相关,对临床上判断预后具有较大的意义。  相似文献   

20.

Background:

Immunohistochemistry (IHC) and fluorescent in situ hybridisation (FISH) are currently the most commonly used methods to assess HER2 status. PCR-based assays allow quantitative determination of HER2 amplification (Q-PCR) or overexpression (Q-RT–PCR), but are not routinely used. We evaluated the relevance of Q-RT–PCR for HER2 status determination.

Methods:

We compared IHC and Q-RT–PCR in 466 breast tumours. In discordant or equivocal cases, five additional methods (IHC with two other antibodies, FISH, silver in situ hybridisation (SISH) and Q-PCR) were combined to determine HER2 status. Two cases with HER2 intra-tumour heterogeneity were further explored by allelic profiles analysis and HUMARA clonality determination after microdissection.

Results:

We observed 97.3% concordance between Q-RT–PCR and non-equivocal IHC. Twelve out of 466 cases (3%) revealed discordances between the two methods. The power of Q-RT–PCR to predict HER2 status (defined by seven methods) was similar to that of IHC. Although rare, some discordances between techniques might be due to HER2 intra-tumour heterogeneity and we report two examples, one tumour containing two distinct clones, another tumour consisting of HER2 amplified and non-amplified subclones.

Conclusion:

Q-RT–PCR and IHC are highly concordant methods for HER2 status assessment, and Q-RT–PCR allows a highly reliable quantitative assessment and could be a useful adjunct to IHC.  相似文献   

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