乳腺癌和非癌组织中Syk、survivin和Ki-67的表达及其相关性

目的 探讨乳腺癌和非癌组织中Syk、survivin和Ki-67的表达及其相互关系.方法 应用免疫组化SP法检测52例乳腺浸润性导管癌和39例非癌组织(包括癌旁乳腺组织17例和乳腺纤维腺瘤组织22例)中Syk、survivin和Ki-67的表达.结果 39例非癌组织中Syk均呈阳性表达,而survivin及Ki-67均呈阴性表达.52例乳腺癌组织中,Syk阳性22例(42.3%),survivin阳性36例(69.2%),Ki-67阳性32例(61.5%).乳腺癌中Syk阳性表达率低于非癌组织(χ2=31.01, P＜0.01);乳腺癌中survivin(χ2=41.82,P＜0.01)和Ki-67(χ2=34.37,P＜0.01)阳性表达率均高于非癌组织.相关分析显示,Syk与survivin的表达呈负相关(r=-0.53,P＜0.01);Syk与Ki-67的表达相关系数呈负值(r=-0.22,P=0.12);survivin与Ki-67的表达呈正相关(r=0.33,P＜0.05).结论 Syk可能有抑制乳腺癌细胞增殖和促进其凋亡的功能,提示Syk可能是一种抑癌基因,可作为乳腺癌新的分子标记物.联合检测Syk、survivin和Ki-67在乳腺癌中的表达,有望成为估价乳腺癌生物学行为的参考指标.     

胃癌及癌旁黏膜组织中CK7、CK20和Ki-67表达的临床意义

目的 研究CK7、CK20和Ki-67在胃腺癌组织中表达状况及临床意义.方法 采用免疫组化EnVision法检测60例胃癌及癌旁黏膜组织CK7、CK20和Ki-67的表达情况,比较不同组织类型胃腺癌患者CK7、CK20和Ki-67的表达及其相关性.结果 胃癌组织中CK7、CK20和Ki-67的阳性表达率分别为88.33%(53/60)、73.33%(44/60)和96.67%(58/60),癌旁黏膜异型增生中CK7、CK20和Ki-67的表达分别为92.31%(24/26)、84.62%(22/26)和96.15%(25/26),肠上皮化生组织中CK7、CK20和Ki67的表达分别为85.71%(12/14)、78.57%(11/14)和92.86%(13/14),均明显高于癌旁正常黏膜组织(P均<0.05),且阳性强度多为高表达.低分化胃腺癌中CK7、CK20和Ki-67的表达明显强于高分化腺癌,差异具有统计学意义(P＜0.05).CK7、CK20和Ki-67在胃腺癌组织中的表达呈正相关(P＜0.001).结论 CK7、CK20和Ki-67的表达与胃癌分化程度关系密切,可作为预测胃癌评估预后的指标.     

非小细胞肺癌中Ki-67和BCL-2表达的临床意义及预后价值

目的 探讨细胞增殖核抗原Ki-67蛋白及凋亡调节因子BCL-2蛋白在非小细胞肺癌(non-small cell lung carcinoma,NSCLC)中表达.方法 采用组织芯片技术用Ki-67和BCL-2单克隆抗体对261例NSCLC标本进行免疫组化染色.结果 Ki-67增殖指数为61.3%,在8例正常对照组织中呈阴性;Ki-67蛋白表达在高分化组明显低于低分化组、淋巴结转移阳性组明显高于淋巴结转移阴性组,差异均有显著性(P＜0.01);Ki-67表达与患者年龄、性别、组织类型和T分期无关;Ki-67阳性组患者平均存活月数明显低于阴性组,差异有显著性(P<0.01).BCL-2蛋白阳性率为43.68%,对照组阴性;BCL-2在低分化组和淋巴结转移阳性组分别低于高分化组和淋巴结转移阴性组,差异均无显著性(P>0.05);BCL-2阳性组患者平均存活月数高于阴性组患者,差异无显著性(P>0.05);BCL-2蛋白表达与患者年龄、性别、组织学类型、T分期无关;114例BCL-2阳性患者中Ki-67阳性率仅26.88%,而101例Ki-67阴性患者中BCL-2阳性率为70.30%.结论 BCL-2表达与NSCLC临床病理因素无相关性,Ki-67与BCL-2表达呈明显负相关.Ki-67蛋白作为细胞增生标志与NSCLC淋巴结转移相关,Ki-67阳性者预后差,Ki-67可作为判断NSCLC预后的一个有价值的分子标志.     

结直肠腺癌组织survivin和Ki-67的表达及其与预后的关系

目的探究存活蛋白(survivin)和Ki-67在结直肠腺癌中的表达及与预后的关系。方法用免疫组化SP法和原位杂交法检测survivin和Ki-67蛋白在30例正常结直肠组织、60例结直肠腺癌中的表达水平,分析survivin和Ki-67与病理参数及结直肠癌预后的关系。结果 60例结直肠癌组织中survivin和Ki-67蛋白阳性表达分别为73.34%(44/60)和80.00%(48/60),显著高于30例癌旁正常组织中的10.00%(3/30)和6.67%(2/30),(P0.01);survivin mRNA在结直肠癌组织、癌旁正常组织中阳性表达分别为76.67%、6.67%;survivin和Ki-67在结直肠癌组织中的表达呈正相关(P0.05)。Survivin、Ki-67的表达与结直肠癌的TNM分期、肠壁侵润深度、淋巴结转移、肝转移和腹腔微转移均呈正相关(P0.05)。survivin和Ki-67阳性表达患者1、3和5年生存率较低。survivin、Ki-67、TNM分期、淋巴结转移、肝转移和腹腔微转移是结肠癌患者预后的独立危险因素。结论 Survivin和Ki-67的异常表达与结直肠腺癌发生、发展及预后密切相关,其有望成为结直肠癌诊疗的新靶点。     

肝细胞癌中HBO1和Ki-67表达的相关性及其临床意义

目的探讨HBO1和Ki-67在人肝细胞癌中表达的相关性及其临床意义。方法采用免疫组化En Vision法检测142例肝细胞癌及对应癌旁组织中HBO1和Ki-67的表达,分析两者表达的相关性及其与临床病理特征和预后的关系。结果肝细胞癌组织中HBO1和Ki-67的阳性率分别为69.0%(98/142)和55.6%(79/142),明显高于癌旁组织24.6%(35/142)和19.7%(28/142),差异有统计学意义(P0.05);两者的表达呈明显正相关(r_s=0.505,P0.05);HBO1和Ki-67高表达均与肿瘤大小、分化程度、TNM分期及门静脉癌栓密切相关(P0.05);Kaplan-Meier生存分析显示,HBO1、Ki-67高表达组患者的生存时间明显低于低表达组(P0.05);Cox多因素分析显示,患者预后与HBO1高表达、Ki-67高表达、TNM分期及门静脉癌栓显著相关(P0.05)。结论 HBO1和Ki-67表达与肝细胞癌的发展关系密切相关,两者联合检测可以用于预测肝细胞癌的恶性程度和预后的评估。     

胃癌及癌旁组织中CDX2和claudin-3的表达及其意义

目的探讨CDX2和claudin-3在胃癌及癌旁组织中的表达及其与临床病理因素之间的关系。方法采用免疫组化SP法检测CDX2和claudin-3在67例胃癌及32例癌旁组织中的表达。结果 (1)CDX2在癌旁正常组织中不表达,癌旁肠化上皮的阳性率(87.5%)明显高于胃癌组织(44.8%,P<0.001)。CDX2在Lauren分型肠型胃癌中的阳性率(62.9%)明显高于弥漫型胃癌(25.0%,P<0.05);CDX2表达与胃癌分化程度呈正相关(P<0.05),而与淋巴结转移和TNM分期呈负相关(P<0.05)。claudin-3在胃癌组织中的阳性率(77.6%)明显高于癌旁正常组织(36.7%,P<0.001),胃癌中claudin-3仅与淋巴结转移呈正相关(P<0.05)。(2)5年生存分析显示:CDX2阳性组胃癌5年生存率(76.7%)明显高于阴性组(43.2%,P=0.01)。claudin-3与胃癌患者5年生存率无明显相关性(P>0.05)。根据CDX2和claudin-3在胃癌中联合表达结果进行生存分析,结果显示CDX2+/claudin-3-的胃癌患者,5年生存率最高(P=0.004)。多因素回...     

结直肠癌中GRHL3、E-cadherin和Ki-67的表达及临床意义

目的探讨粒状头样3(Grainyhead-like 3,GRHL3)与E-cadherin和Ki-67在结直肠癌中的表达及临床意义。方法采用免疫组化SP法检测100例结直肠癌组织及30例癌旁正常组织中GRHL3、E-cadherin和Ki-67的表达,分析三者表达的相关性及与临床病理特征、预后的关系。结果结直肠癌组织中GRHL3和Ki-67阳性率(64.0%和60.0%)高于癌旁正常组织(30.0%和6.7%),E-cadherin阳性率(55.0%)低于癌旁正常组织(99.7%),差异均有统计学意义(P<0.05)。结直肠癌组织中GRHL3和Ki-67的表达与肿瘤大小密切相关,GRHL3和E-cadherin的表达与TNM分期、浸润深度及淋巴结转移密切相关,差异均有统计学意义(P<0.05);GRHL3与E-cadherin的表达呈负相关(χ²=6.674,P=0.010,rs=-0.260),与Ki-67的表达呈正相关(χ²=7.799,P=0.005,rs=0.281)。GRHL3和Ki-67阳性患者5年生存率低于阴性患者(P<0.001,P=0.017),E-cadherin阴性患者5年生存率低于阳性患者(P<0.001);多因素Cox回归分析显示,TNM分期Ⅲ+Ⅳ期、GRHL3阳性及E-cadherin阴性是影响结直肠癌患者预后的独立危险因素(P<0.05)。结论GRHL3在结直肠癌中高表达,且可能与E-cadherin和Ki-67之间存在一定相互作用,三者共同参与结直肠癌的发生发展和侵袭转移过程。     

甲状腺乳头状癌组织中E-cadherin、β-catenin 和cyclinD1蛋白表达及意义

目的 探讨甲状腺乳头状癌组织中E-cadherin、β-catenin和cyclinD1蛋白表达对其发生、发展的影响.方法 应用免疫组化EnVision法检测36例甲状腺乳头状癌组织、27例甲状腺腺瘤旁组织E-cadherin、β-catenin 和cyclinD1的蛋白表达,同时分析三者表达水平的变化与其它病理参数的关系.结果 E-cadherin在甲状腺乳头状癌的表达下降,阳性率为30.56%(P<0.05),与肿瘤淋巴结转移相关(P<0.01);β-catenin在癌组织中细胞核/核周区呈强阳性表达,且表达率明显升高为80.56%(P<0.01),其异常表达与肿瘤淋巴结转移相关(P<0.01);cyclinD1在癌组织中的阳性表达率为72.22%(P<0.01),与肿瘤淋巴结转移有关(P<0.05).此外,E-cadherin的低表达与cyclinD1的过表达呈负相关(P<0.05),β-catenin的异位高表达与cyclinD1的过表达呈正相关(P<0.05).结论 E-cadherin表达缺失和β-catenin异位高表达可能通过诱导cyclinD1的过表达,进而影响甲状腺乳头状癌的发生和发展.     

PAK5与乳腺癌分子分型及临床病理特征的相关性分析

目的探讨PAK5表达与乳腺癌分子分型及临床病理特征的相关性。方法采用免疫组化法检测乳腺癌组织中PAK5、ER、PR、HER2、Ki-67表达并评分,应用荧光原位杂交(fluorescence in situ hybridization, FISH)进一步检测免疫组化HER2 2+的乳腺癌组织中HER2基因扩增情况,分析PAK5表达与乳腺癌分子分型、TNM分期、肿块大小、淋巴结转移等的关系。结果根据HER2基因有无扩增分别纳入HER2阳性组和阴性组。与癌旁组织相比,PAK5在乳腺癌组织中的表达增加;PAK5高表达与患者肿块较大、淋巴结转移、TNM高分期等呈正相关(P0.05);PAK5高表达与患者生存率低相关(P0.05);PAK5表达与ER、PR表达呈负相关,与Ki-67表达呈正相关(P0.05);与非三阴型乳腺癌相比,PAK5在三阴型乳腺癌中的表达增加,差异有统计学意义(P0.05)。结论 PAK5在乳腺癌组织中的表达增加,且与乳腺癌分子分型、TNM分期及不良预后密切相关,PAK5有望成为临床治疗乳腺癌的新靶点。     

胰岛素样生长因子-1受体和血管内皮生长因子在胃癌中的表达

目的: 探讨胰岛素样生长因子1受体(IGF-1R)和血管内皮生长因子受体(VEGF)的表达与胃癌浸润、转移的关系.方法: 选取胃癌患者56例, 以20例癌旁不典型增生组织及28例正常胃黏膜组织作为对照, 应用SABC免疫组化方法检测IGF-1R和VEGF的表达.结果: IGF-1R蛋白在胃癌组织、癌旁不典型增生组织及正常胃黏膜组织中的阳性表达率分别为87.5%、 55.00%和17.86%, 两两比较, 均有统计学差异(P<0.01);IGF-1R蛋白在胃癌转移组和无转移组中的阳性表达率分别为97.06%和72.73%(P<0.05);浸润至黏膜下层、肌层、外膜的胃癌组织中IGF-1R蛋白阳性表达率分别为66.67%、 92.59%、 100%(P<0.05).VEGF蛋白在胃癌组织、癌旁不典型增生组织及正常胃黏膜组织中的阳性表达率分别为69.64%、 45.00%和25.00%, 两两比较, 均有统计学差异(P<0.05);VEGF蛋白在胃癌转移组和无转移组中的阳性表达率分别为85.29%和45.45%(P<0.01);浸润至黏膜下层、肌层、外膜的胃癌组织中VEGF蛋白阳性表达率分别为40.00%、 74.07%、 85.71%(P<0.05).结论: IGF-1R和VEGF与胃癌的发生、浸润、转移有关, 可联合运用, 作为新的胃癌标记物, 对判断预后有一定价值.     

Overexpression of phosphorylated histone H3 is an indicator of poor prognosis in gastric adenocarcinoma patients.

Ki-67 immunostaining is commonly used for assessing cell proliferation, but studies of its use as a prognostic indicator have revealed discordant results in gastric cancer patients. Recently, antibodies for phosphorylated histone H3 have been used to identify dividing cells because of its precise overexpression in mitosis. The authors tested the hypothesis that phosphorylated histone H3 overexpression might be a good prognostic indicator for gastric cancer patients by conducting an immunohistochemical comparison with Ki-67 in gastric cancer samples. One hundred twenty-two surgically resected primary cases were selected and histologically categorized in accordance with Lauren's classification. No correlation was found between phosphorylated histone H3 and Ki-67 regarding overexpression. However, correlations between phosphorylated histone H3 overexpression and clinicopathologic variables were noted for histologic type (intestinal type predominant in high labeling indices [LIs], defined as over the value of the 75th percentile; P<0.01), vessel invasion (positive in high LIs; P=0.05), and lymph node metastasis (positive in high LIs; P=0.04). With regard to Ki-67 overexpression, no correlation was evident with the clinicopathologic variables except histologic type (intestinal type predominant; P=0.05). By the Kaplan-Meier method with the log-rank test, cases overexpressing phosphorylated histone H3 showed a poorer prognosis than cases with low expression (P<0.01). In contrast, Ki-67 expression did not influence prognosis. Multivariate analyses indicated phosphorylated histone H3 overexpression to be an independent prognostic factor, together with lymphatic invasion and venous invasion (P<0.01). In conclusion, it seems likely that phosphorylated histone H3 plays an important role in the prognosis of gastric cancer, and its immunohistochemical investigation is useful for the prediction of prognosis in gastric cancer.     

OVEREXPRESSION OF DIFFERENT MEMBERS OF THE TYPE 1 GROWTH FACTOR RECEPTOR FAMILY AND THEIR ASSOCIATION WITH CELL PROLIFERATION IN PERIAMPULLARY CARCINOMA

The expression of epidermal growth factor receptor (EGFR), c- erb B-2, and c- erb B-3 was examined immunohistochemically in 57 cases of periampullary carcinoma. The percentage of Ki-67-positive cells was also examined in the same tissue, to determine the relationship between the expression of the members of the type 1 growth factor receptor family and cell proliferation. In carcinoma of the head of pancreas, the percentage of cases with overexpression of c- erb B-3 was significantly higher than with overexpression of c- erb B-2 and EGFR. In contrast, in lower bile duct carcinoma and carcinoma of the ampulla of Vater, the percentages of cases with overexpression of c- erb B-2 was greater than with overexpression of other growth factor receptors. A higher percentage of cases with overexpression of c- erb B-3 in pancreatic head carcinoma and overexpression of c- erb B-2 in carcinoma of the ampulla of Vater was found in Ki-67 antigen-positive cases. Moreover, the overexpression of c- erb -3 in pancreatic head carcinoma, c- erb -2 in ampulla of Vater carcinoma, and Ki-67 in both carcinomas was found to be associated with poor patient outcome. These results demonstrate that different members of the type 1 growth factor receptor family are overexpressed in different carcinomas of the periampullary region.     

Different roles of p53 between Epstein-Barr virus-positive and -negative gastric carcinomas of matched histology

To clarify the role of p53 in the development of Epstein-Barr virus (EBV)-associated gastric carcinoma, we examined DNA-ploidy pattern, the immunoreactivity of p53, p21(WAF1) and Ki-67 and the incidence of mitosis and apoptosis in EBV-positive and -negative gastric carcinomas of similar histology: a lace pattern and/or gastric carcinoma with lymphoid stroma. There was no significant difference in DNA-ploidy pattern, Ki-67 index or frequencies of mitosis and apoptosis between the two groups. In deeply invasive tumours (involving the muscularis propria or deeper), p53-positive ones were rare in the EBV-encoded small RNA (EBER)-positive group and very common in the EBER-negative group, while in superficial tumours, around one-half of them were p53-positive in both groups. In p53-positive superficial tumours, p21(WAF1)-positive ones accounted for 80% in the EBER-positive group and were scarce in the EBER-negative group. It is thus possible that p53 immunoreactivity reflects the overexpression of wild-type p53 and the stabilization of mutant p53 in the EBER-positive and -negative groups, respectively. The role of p53 in tumour development seems to be smaller in EBER-positive than in -negative gastric carcinomas.     

Expression of Bcl-2 and p53 correlates with the morphology of gastric neoplasia

The growth of a tumour can be determined by an interplay between cell proliferation and loss. The expression of apoptosis-related proteins (Bcl-2 and p53), cell proliferation (Ki-67), and apoptotic cell death were investigated using immunohistochemistry and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling in gastric neoplams, to evaluate whether they correlate with the morphology of the tumour. The materials included ten cases of gastric adenoma and 40 cases of early gastric carcinoma consisting of differentiated adenocarcinomas (n=20) and undifferentiated carcinomas (n=20). All cases of adenoma and eight cases of differentiated adenocarcinoma were of the elevated type, while 12 differentiated adenocarcinomas and all of the undifferentiated carcinomas were of the depressed type. The diffuse expression of Bcl-2 was observed in all cases of adenoma and seven out of eight (88 per cent) of elevated-type differentiated adenocarcinoma. In contrast, Bcl-2 expression was absent or focal in the depressed type of carcinoma. Overexpression of p53 was found exclusively in the depressed type of carcinoma. Thus, Bcl-2 and p53 expression was associated with tumour morphology. It seemed unlikely that Bcl-2 and p53 expression was involved in the morphogenesis of the gastric tumours through inhibiting apoptotic cell death, since the degree of apoptosis in Bcl-2-positive gastric tumours was rather higher than that in Bcl-2-negative ones and it did not differ significantly between p53-positive and p53-negative tumours. Instead, the diffuse distribution of Bcl-2 correlated with the superficial distribution of Ki-67-positive proliferating cells, and the overexpression of p53 had a tendency to correlate with the diffuse distribution of proliferating cells. These results suggest that diffuse Bcl-2 expression and a superficial distribution of proliferating cells may contribute to the elevated configuration, and that overexpression of p53 and a diffuse distribution of proliferating cells may result in the depressed configuration in the relatively early stages of gastric tumourigenesis. © 1998 John Wiley & Sons, Ltd.     

Expression of cyclins,p53, and Ki-67 in cervical squamous cell carcinomas: overexpression of cyclin A is a poor prognostic factor in stage Ib and II disease

We previously reported the overexpression of cyclins in uterine cervical carcinoma; however, their clinicopathological significance remained undetermined. In the present study, we examined the immunohistochemical expression of cyclins (D1, E, A, B1), p53 and Ki-67 in squamous cell carcinoma (stage Ib+II; 80 cases, stage III+IV; 23 cases). Correlations between the expression of cyclins and clinicopathological parameters and patient survival were statistically evaluated. The results indicated that in the normal squamous epithelium, the expression of cyclins and Ki-67 was sporadically observed in the parabasal layer. Of the 103 cervical carcinomas, overexpression of cyclins D1, E, A, B1 and p53 was observed in 13 (13%), 23 (22%), 25 (24%), 18 (18%) and 23 (22%) cases, respectively, with a slight predominance in advanced stage tumors. The expression of cyclin D1, E, A and p53 significantly correlated with that of Ki-67 (Spearmans rank correlation). Univariate and multivariate analyses revealed that lymph node metastasis and cyclin A overexpression were independent prognostic factors for unfavorable outcomes in stage Ib+II patients. These findings suggest that the overexpression of various cyclins is involved in the acquisition of the vigorous growth potential of cervical carcinoma cells, and that cyclin A is an independent prognosticator of cervical carcinoma in early stages.     

卵巢低、高级别浆液性癌的临床病理分析及Pax2、p53和Ki-67表达的意义

目的 初步评估卵巢浆液性癌的两级分级系统在病理诊断和预后判断中的应用价值,探讨低、高级别浆液性癌Pax2、p53和Ki-67的表达及其与预后的相关性.方法 依照两级分级系统对卵巢浆液性癌进行分级,分别选取低级别癌38例,高级别癌100例,观察其临床病理特点,并采用免疫组织化学EnVision法检测癌组织中Pax2、p53和Ki-67的表达情况.结果 (1)低级别组的总生存时间、无病生存时间和5年生存率均显著优于高级别组(P＜0.05).(2)低级别组Pax2的阳性率显著高于高级别组(65.8%比13.0%,P＜0.05),而p53强阳性率显著低于高级别组(13.2%比55.0%,P＜0.05),Ki-67阳性指数显著低于高级别组(13.7%比42.1%,P＜0.05).(3)Pax2阳性组的总生存时间和5年生存率均显著优于阴性组(P＜0.05),而无病生存时间的差异无统计学意义(P＞0.05).p53和Ki-67阳性指数与生存时间的差异无统计学意义(P＞0.05).结论 两级分级系统对卵巢浆液性癌的预后判断有提示意义,在临床病理诊断中具有可行性.Pax2、p53和Ki-67在卵巢低、高级别浆液性癌中的表达差异有统计学意义.与p53和Ki-67相比,Pax2更有可能成为卵巢浆液性癌的一个预后相关指标.

Abstract：

Objective To evaluate the two-tier system for the grading of ovarian serous carcinomas,and to analyze Pax2, p53, Ki-67 protein expression and their prognostic values for low- and high-grade ovarian serous carcinomas. Methods A total of 38 cases of low-grade and 100 cases of high-grade ovarian serous carcinomas were selected based on the two-tier grading system. Innnunohistochemistry was used to detect Pax2, p53 and Ki-67 protein expression in all cases. Correlation of the two-tier system with immunohistochemical results and prognostic parameters were performed. Results ( 1 ) The overall survival,disease-free survival and 5-year survival rates were significantly higher in the low-grade serous carcinoma cases than in the high-grade cases ( P ＜ 0. 05 ). (2) Significant differences in protein expressions were found between the low- and high-grade serous carcinomas. The high-grade serous carcinomas had a significantly higher expression level of p53 (55.0% vs 13. 2%, P ＜ 0. 05 ) and Ki-67 (42. 1% vs 13.7%, P ＜ 0. 05 ),while low-grade carcinomas had a significantly higher expression level of Pax2 (65. 8% vs 13.0%,P ＜ 0. 05 ). (3) Pax2 positive cases had a significantly better overall survival and 5-year survival rates than Pax2 negative cases ( P ＜ 0. 05 ). The expressions of p53 and Ki-67 were found to have little correlation with overall survival and disease-free survival( P ＞ 0. 05 ). Conclusions The two-tier system for the grading of ovarian serous carcinomas has a good prognostic value. There are significantly differences in expressions of Pax2, p53 and Ki-67 between low- and high-grade ovarian serous carcinomas. Compared with p53 and Ki-67, Pax2 is likely a better prognostic indicator for ovarian serous carcinoma.     

Pathobiological characteristics of intestinal and diffuse-type gastric carcinoma in Japan: an immunostaining study on the tissue microarray

AIM: To investigate the pathobiological features of intestinal and diffuse-type gastric carcinomas in the Japanese population. METHODS: The expression of fragile histine triad (FHIT), phosphatase and tensin homology deleted from human chromosome 10 (PTEN), caspase-3, Ki-67, mutant p53, matrix metalloproteinase (MMP)-2, MMP-9, and extracellular matrix metalloproteinase inducer (EMMPRIN) on tissue microarrays of gastric carcinomas by immunostaining was examined in comparison with the clinicopathological characteristics between intestinal and diffuse-type cases. RESULTS: Intestinal-type carcinoma frequently occurred in old men, whereas the diffuse type comparatively occurred more in young women (p<0.05). The diffuse-type carcinoma was more inclined to invasion into muscularis propria, lymphatic invasion and lymph node metastasis, and belonged to higher International Union against Cancer (UICC) staging (p<0.05) compared with intestinal-type counterparts. Expression of FHIT, PTEN, Ki-67, caspase-3, mutant p53 and EMPPRIN was higher in intestinal-type carcinomas than in diffuse-type carcinomas (p<0.05). Kaplan-Meier analysis indicated that patients with intestinal-type carcinomas had a higher cumulative survival rate (p<0.05). CONCLUSION: Intestinal-type gastric carcinomas with a more favourable prognosis frequently show high levels of proliferation and apoptosis, and always accompany strong expression of FHIT, PTEN and mutant p53 and EMMPRIN. EMMPRIN expression might underlie the molecular basis of liver metastasis and higher proliferation of intestinal-type gastric carcinomas in Japan. Lauren's classification thus proved pathologically relevant for the clinical treatment of gastric carcinomas.     

Thioredoxin, a putative oncogene product, is overexpressed in gastric carcinoma and associated with increased proliferation and increased cell survival

Human thioredoxin is a putative oncogene that may confer both a growth and survival advantage to tumor cells. Overexpressed thioredoxin mRNA has been found in both primary human lung and colorectal cancers. To determine the intratumor distribution and amount of thioredoxin protein in human primary carcinomas, we developed an immunohistochemical assay for thioredoxin in paraffin-embedded tissue. We then studied 10 patients with primary high-risk gastric carcinoma. To further relate thioredoxin protein overexpression to cell death and survival, we used a paraffin-based in situ end-labeling (ISEL) assay. To delineate proliferation, we used the nuclear proliferation antigen detected by Ki-67. In this survey, we found that thioredoxin was localized to tumor cells and overexpressed compared with normal gastric mucosa in 8 of 10 gastric carcinomas. The thioredoxin was found at high levels in 5 of the 8 overexpressing carcinomas. The overexpression of thioredoxin was typically found in both a nuclear and cytoplasmic location in the neoplastic cells. There was a significant positive correlation (P = .0061) with cancer cell proliferation measured by Ki-67. There was a significant negative correlation (P = .0001) with DNA damage measured by the ISEL assay, suggesting decreased apoptosis and increased carcinoma cell survival. Thus, human primary gastric tumors that are highly expressive of thioredoxin have both a higher proliferative rate and a higher survival rate than tumors that do not express thioredoxin. With these newly developed assays in hand, it is now feasible to question whether this thioredoxin-related combined growth and survival advantage translates into poor clinical outcome.