E—钙黏蛋白及α、β—连接蛋白表达与大肠癌细胞增殖的关系

目的 :探讨E 钙黏蛋白 (E cad)及其相关蛋白α 连接蛋白 (α cat)、β 连接蛋白 (β cat)的表达与大肠腺癌细胞增殖的关系。方法 :用S P免疫组化方法检测 5 1例大肠腺癌中E cad、α cat、β cat的表达 ,分析其表达状况与Ki6 7标记指数 (LI)的相关性。结果 :5 1例大肠癌Ki 6 7LI为 44 7± 18 8( x±s)。 3种蛋白正常表达组与减低表达组Ki6 7LI分别为 :5 2 7± 17 5 ,38 7±17 7(E cad) ;5 0 2± 19 3 ,40 9± 17 8(α 连接蛋白 ) ;49 2± 18 2 ,42 7± 18 9(α 连接蛋白 )。E cad表达与癌细胞Ki6 7LI呈正相关 (P <0 0 5 ) ,α cat、β cat表达则与LI无关 (P >0 0 5 )。 结论 :E cad可能参与大肠腺癌细胞增殖的调节     

p53、p21~(WAF1)蛋白在非小细胞肺癌中的表达及其临床意义

目的　探讨原发性非小细胞肺癌中p5 3、p2 1WAF1蛋白表达与临床病理及预后的关系。方法　应用免疫组织化学 (SP法 )方法。共检测非小细胞肺癌 147例 ,其中腺癌 6 6例 ,鳞癌 6 3例 ,腺鳞癌 14例 ,大细胞癌 4例。结果　p5 3蛋白总阳性率为 6 1.2 % (90 / 147) ,腺癌为 5 7.6 % (38/ 6 6 ) ,鳞癌阳性率为 6 3.5 % (4 0 / 6 3) ,腺鳞癌为 71.4% (10 / 14) ,大细胞癌 2例阳性。p2 1WAF1蛋白总阳性率为40 1% (5 9/ 147) ,腺癌为 42 .4% (2 8/ 6 6 ) ,鳞癌为 41.3% (2 6 / 6 3) ,腺鳞癌 2 8.6 % (4 / 14) ,大细胞癌 1例阳性。肺腺癌p5 3蛋白阳性表达与其预后相关 ,6 6例腺癌中 ,生存率低于 3年组和高于 3年组的p5 3蛋白阳性率分别为 75 % (2 1/ 2 8)和 44 .7% (17/ 38) ,差异有显著性意义 (P <0 .0 2 5 )。p2 1WAF1阳性表达与肺癌预后有关 ,p2 1WAF1阳性表达者 3年生存率 (6 4.4% )高于阴性表达者 (4 6 .6 % ) (P <0 .0 5 )。p5 3阳性而p2 1WAF1阴性的非小细胞肺癌患者的预后比p5 3阴性而p2 1WAF1阳性者差 (P <0 .0 1)。结论　检测p5 3蛋白表达可作为判断肺腺癌预后的指标之一 ;检测p2 1WAF1蛋白表达有利于对非小细胞肺癌预后的判断 ;联合检测p5 3、p2 1WAF1蛋白对判断非小细胞肺癌的预后有重要的意义 ,似可作     

非小细胞肺癌p63基因的表达及其与3号染色体位点变化的关系

目的　探讨非小细胞肺癌 p6 3基因的蛋白表达水平及其与定位在 3号染色体 2 7～ 2 9区域改变的关系。 方法　应用比较基因组杂交 (CGH)技术对 70例原发性肺鳞状细胞癌和肺腺癌标本进行染色体不平衡性分析。采用组织芯片技术构建12 2例原发性非小细胞肺癌石蜡包埋标本组织芯片 ,并采用免疫组织化学方法检测p6 3蛋白表达情况。比较 p6 3蛋白表达及其与 3号染色体末端改变的关系。结果　CGH分析结果发现 ,30例鳞状细胞癌 2 4例出现 3q2 7～ 2 9区域DNA拷贝数目的增加 ,4 0例腺癌仅 8例发现 3q2 7～ 2 9区域DNA获得。p6 3免疫组化染色结果显示 :5 0例 (84 75 % )鳞状细胞癌免疫组化染色为阳性 ;3例大细胞肺癌中 2例 (6 6 6 6 % )为阳性反应 ;腺癌中仅有 1例 (1 6 7% )为阳性。p6 3蛋白的阳性表达率与患者的年龄、性别、肿瘤的分级、肿瘤的转移以及生存率无关 (P >0 0 5 )。p6 3免疫组化阳性率与 3q2 7～ 2 9区域的改变比较结果显示 :p6 3免疫组化阳性反应与 3号染色体长臂 2 7～ 2 9区域的DNA扩增呈正相关 (P <0 0 1)。结论　p6 3基因的扩增与肺鳞状细胞癌发生和发展有密切的关系     

新疆维吾尔族与汉族结直肠癌组织P53表达的差异

目的　研究新疆维吾尔族 (维族 )和汉族、浙江汉族结直肠癌组织中 p5 3、Ki 6 7、COX 2蛋白的表达 ,探讨其表达上的差异。方法　应用免疫组化S P法对 14 4例结直肠癌组织 (新疆维族 38例和汉族 5 2例、浙江汉族 5 4例 )中p5 3、Ki 6 7、COX 2蛋白表达进行检测。结果　 3组结直肠癌患者性别构成差异无统计学意义。维族结直肠癌发病年龄早于两组汉族 (浙江汉族、新疆汉族和维族病人的年龄分布分别为 5 7 7± 12 6、5 7 0± 11 5、5 1 4± 11 2岁 ,经方差分析 ,F =3 5 2 0 ,P <0 0 5 )。组织学类型 :浙江汉族病人管状腺癌占 82 7% ,新疆汉族和维族病人乳头状腺癌所占的比例高于浙江汉族 ,3组间差异有显著性(P <0 0 5 )。结直肠癌间分化程度 :新疆汉族高于其他两组 (P <0 0 1)。调整年龄、性别因素后经多因素Logistic回归模型分析 ,民族与结直肠癌p5 3蛋白的阳性表达有关。维族 p5 3阳性率高于汉族 ,比值比为 2 4 92 (95 %CI 1 0 4 6～ 5 939)。新疆汉族和维族结直肠癌与Ki 6 7和COX 2蛋白表达无相关性。结论　维族结直肠癌 p5 3蛋白表达高于汉族病人 ,其意义值得进一步探讨。     

非小细胞肺癌组织中细胞凋亡与p53蛋白表达的定量研究

目的 :观察非小细胞肺癌 (NSCLC)组织中Caspases介导的细胞凋亡与p5 3蛋白表达情况 ,探讨两者之间的相关关系和意义。方法 :临床手术切除的NSCLC标本 4 4例 ,其中鳞癌 2 0例 ,腺癌 2 4例。采用Caspase特异的单克隆抗体M30Cy toDEATH免疫组化染色显示凋亡细胞 ,计算凋亡指数 (AI) ;免疫组化法检测p5 3蛋白表达 ,用显微图像分析系统测定阳性细胞百分率 (P/A)、平均光密度 (AOD)及阳性水平指数 (PLI)。结果 :NSCLC组织中M30阳性率为 2 5 0 % ,肺鳞癌组织的M 30阳性率明显高于肺腺癌组织 (P <0 0 5 )。低分化鳞癌组织的AI高于中、高分化鳞癌 (P <0 0 5 )。NSCLC组织中 p5 3蛋白阳性率为 5 2 2 %。p5 3蛋白的PLI与癌细胞AI之间无直线相关关系。 结论 :在NSCLC组织中存在Caspases介导的细胞凋亡机制 ,且与组织学类型及组织分化程度有关。p5 3蛋白表达与癌细胞凋亡无相关关系 ,提示突变型 p5 3蛋白失去了激活Cas pases而诱导细胞凋亡的作用 ,与肺癌的发生、发展、治疗及预后有关。     

口腔鳞癌及癌前病变组织中p27、p53蛋白的表达

目的　探讨 p2 7、p5 3蛋白表达在口腔鳞癌发生发展中的意义。 方法　应用免疫组化S P法分别检测 9例口腔正常黏膜 ,11例单纯性增生、2 6例癌前病变及 5 4例鳞癌组织中p2 7、p5 3蛋白的表达。 结果　p2 7蛋白在口腔正常黏膜和单纯性增生组织中呈高表达 ,在癌前病变和鳞癌组织中高 (低 )表达率分别为 6 1 5 % (38 5 % )、2 5 9% (6 1 1% ) ,在鳞癌中阴性表达率为 13% ;p2 7蛋白的表达与鳞癌的组织分化程度、临床分期相关 (P <0 0 5 )。p5 3蛋白在正常黏膜、单纯性增生及轻、中度不典型增生中未见表达 ,在重度不典型增生和鳞癌中可见 2 8 6 %和 4 8 1%的阳性表达 ,二者差异有高度显著性 (P <0 0 1) ;在鳞癌中 p5 3蛋白表达与组织分化程度相关 (P <0 0 5 ) ;p2 7和p5 3表达在鳞癌中呈负相关 (P <0 0 1)。 结论　p2 7蛋白表达的减少在口腔鳞癌的发生发展中起着重要作用 ,并与其预后因素密切相关。p5 3蛋白的表达在癌前病变向鳞癌转变过程中起重要作用。综合分析 p2 7、p5 3表达有助于口腔鳞癌的早期诊断和患者预后的估计。     

p170、p27在非小细胞肺癌的表达及其与化疗的关系

目的：探讨p170,p27在非小细胞肺癌（NSLC）中的表达及化疗对上述两种基因表达的影响,方法：采用免疫组化S－P法检测了3组共56例NSCLC（其中腺癌26例,鳞癌30例）患者p170,p27的表达。结果：（1）末化疗组（A组）p170阳性率为50％（10／20）;化疗后（B组）阳性率为77．78％（14／18）;末化疗但经随访了解以后化疗效果不佳组（C组）为88．89％（16／18）。B、C两组与A组比较差异均有显著性（P＜0．01,P＜0．05）。（2）p27 3组差异无显著性,但肺鳞癌阳性指数（LI）与腺癌及癌周正常支气管上皮3者差异有显著性（P＜0．05）。结论：检测肺癌组织中p170表达对肺癌化疗有重要指导意义,并可提示疗效,p27基因表达与化疗无关,但与组织类型有关。     

宫颈癌中COX-2与p53、E-cadherin蛋白表达的关系

目的　探讨宫颈癌组织中环氧合酶 2 (COX 2 )的表达与 p5 3、E cadherin蛋白表达的关系。 方法　采用免疫组织化学S P法检测 4 1例宫颈癌和 10例正常宫颈上皮组织中COX 2、p5 3、E cadherin蛋白的表达水平。结果　宫颈癌组织中COX 2、p5 3表达水平明显高于正常宫颈上皮 (P <0 .0 1) ,而E cadherin蛋白的表达水平明显低于正常宫颈上皮 (P <0 .0 1) ;COX 2的高表达与宫颈癌淋巴结转移和浸润深度有关 (P <0 .0 5 ) ,与患者年龄、临床分期、组织学类型、分化程度无关 (P >0 0 5 ) ;COX 2表达阳性组 p5 3的表达水平明显高于COX 2表达阴性组 (P <0 0 5 ) ,COX 2表达阳性组的E cadherin蛋白的表达水平则低于相对应阴性组 ,差异有显著性 (P <0 0 5 )。结论　在宫颈癌的发生发展中COX 2、p5 3、E cadherin可能起重要作用。COX 2通过使抑癌基因p5 3失活 ,降低细胞黏附分子E cadherin的水平促进宫颈癌的发生。     

乳腺乳头状瘤病和导管原位癌cyclinD1、p16和Ki-67表达

目的　探讨细胞周期调控因子cyclinD1、p16和Ki 6 7与乳腺乳头状瘤病及导管内癌的相关性及其临床病理意义。方法　通过免疫组化S P法检测轻度乳头状瘤病、重度乳头状瘤病和导管内癌各 4 0例中cyclinD1、p16和Ki 6 7的蛋白表达情况 ,并用 2 0例正常乳腺组织作对照。结果　cyclinD1在轻度、重度乳头状瘤病和导管内癌组中阳性率分别为 2 7 5 %、5 0 0 %、6 0 0 % ,3组间差异有显著性 (χ2 =8 92 9,P <0 0 5 )。p16蛋白表达分别为 80 0 %、5 2 5 %、4 0 0 % ,3组间差异均有显著性 (χ2 =8 6 87,P <0 0 1)。轻度与重度乳头状瘤病组比较均有差异 ,但重度乳头状瘤病与导管内癌组间差异无显著性。Ki 6 7阳性率在 3组间差异有显著性 ,组间两两比较也分别有统计学差异。在各组中 ,Ki 6 7与cyclinD1呈正相关 ,与 p16呈负相关 ,cyclinD1与 p16呈负相关。结论　cyclinD1、p16和Ki 6 7表达异常在乳腺癌发生、发展演进过程中是一种早期事件。重度乳头状瘤病是重要的癌前病变。调节cyclinD1和 p16的平衡可能是癌前病变基因治疗的一条途径     

宫颈鳞状细胞癌HPV16/18、p53、p21表达及意义

目的　探讨人乳头状瘤病毒 (HPV) 16型、18型及 p5 3、p2 1基因蛋白的表达情况以及与宫颈癌的关系。 方法　应用免疫组化二步法检测 5 0例宫颈鳞癌、4 0例正常宫颈黏膜中HPV16、HPV18、p5 3、p2 1的表达。肿瘤组分 <6 0岁和≥ 6 0岁 2个年龄组 ,观察HPV感染情况。结果　宫颈鳞癌中HPV16、HPV18、p5 3、p2 1表达分别为 4 8%、2 0 %、5 4 %和 5 0 % ,而正常宫颈黏膜中的表达分别为 10 %、0、0、10 % ,两者经统计学比较差异有显著性 (P <0 0 1) ;<6 0岁组和≥ 6 0岁组HPV16阳性率分别为 84 2 %和 2 5 8% ,年青组明显高于年老组 ,经统计学比较差异有显著性 (P <0 0 1)。结论　 (1)宫颈鳞癌的发生与HPV16、HPV18感染有密切关系 ,提示检测宫颈HPV16、HPV18感染情况对于宫颈鳞癌的随访和早期诊断有着重要的参考价值。 (2 )提示宫颈黏膜在HPV感染后 ,可能在p5 3、p2 1多种癌基因的共同作用导致宫颈鳞癌的发生发展。     

Expression of cyclin kinase inhibitor p27(Kip1) in skin tumours of dogs

Skin tumours (n=148) of epidermal or hair follicle origin were examined immunohistochemically to determine the expression of p27(Kip1)(p27), a cyclin-dependent kinase inhibitor (CDKI), and of Ki-67. In normal skin, a large number of basal cells of the epidermis and hair follicles were positive for Ki-67 and many suprabasal epithelial cells were positive for p27. Most of the hair matrix cells were positive for Ki-67 but negative for p27. Hair papillae were strongly positive for p27. Squamous cell carcinomas had a p27 positive index (PI) significantly lower than that of trichoepitheliomas (P<0.005), basal cell tumours (P<0.05) and intracutaneous cornifying epitheliomas (P<0.001). In contrast, Ki-67 PIs of squamous cell carcinomas and pilomatrixomas were significantly higher than those of trichoepitheliomas, basal cell tumours and intracutaneous cornifying epitheliomas (P<0.01 to P<0.001). No significant difference was observed between the Ki-67 PI values of squamous cell carcinomas and pilomatrixomas. The results suggested that p27 is capable of suppressing cell proliferation in the differentiation of normal canine skin. In spite of being a benign neoplasm, pilomatrixomas had a low p27 expression; this may be a reflection of the proliferative potential of the hair matrix. The expression of p27 may be a useful marker for the analysis of cell kinetics.     

MCM2 and Ki-67 expression in human lung adenocarcinoma: prognostic implications.

OBJECTIVE: The expressions of minichromosome maintenance protein 2 (MCM2), Ki-67, and p53 were examined to analyze their pathobiological significance in human lung adenocarcinomas. METHODS: We performed Western blot analysis in six human lung adenocarcinoma cell lines and immunohistochemistry in 145 surgically removed adenocarcinomas to examine the MCM2 expression. Labeling indices (LIs; %) of MCM2, Ki-67, and p53 in the tumor cells were compared with clinicopathological profiles and overall survival rates. RESULTS: MCM2 protein was detected in all cell lines examined, with specific bands. MCM2 LIs were significantly correlated with sex, histological type, differentiation, pathological stage, and LIs of Ki-67 and p53 (p < 0.05). Significantly higher LIs of MCM2 and Ki-67 were noted in the 122 non-pure bronchioloalveolar carcinomas than in the 23 pure bronchioloalveolar carcinomas (p < 0.01), and the prognosis was poorer in the former than in the latter (p < 0.01). Sex, pathological stage, and high LIs of MCM2 and/or Ki-67 were independent prognostic factors (p < 0.05). CONCLUSION: High LIs of MCM2 and/or Ki-67 suggest a poor prognosis in patients with lung adenocarcinoma (non-pure bronchioloalveolar carcinoma).     

High frequency of coexpression of maspin with p63 and p53 in squamous cell carcinoma but not in adenocarcinoma of the lung

Maspin, a member of the serpin family of protease inhibitors, has been shown to inhibit tumor growth and suppress metastasis in several malignancies, including lung cancer. Previous studies have reported that p63 and p53 control maspin expression by transactivating the promoter. The present study analyzed immunohistochemical studies to determine the expression and coexpression patterns of maspin, p63 and p53 in non-small cell lung carcinoma, specifically squamous cell carcinoma and adenocarcinoma. The results showed that 83/86 cases (96.5%) of squamous cell carcinoma and 82/161 cases (50.9%) of adenocarcinoma included in this study were positive for maspin. There were 79/86 cases (91.9%) of squamous cell carcinoma and 16/161 cases (9.9%) of adenocarcinoma with positive expression for p63. In addition, 77/86 cases (89.5%) of squamous cell carcinoma and 99/161 cases (61.5%) of adenocarcinoma were positive for p53. Maspin, p63 and p53 expression were each significantly higher in squamous cell carcinoma than adenocarcinoma. Squamous cell carcinomas more highly coexpress maspin and p63, as well as maspin and p53, when compared with adenocarcinomas. The high frequency of coexpression of maspin and p63, as well as maspin and p53, in squamous cell carcinoma, suggests that p63 and p53 may be involved in the pathway to control maspin expression. Therapeutic targeting on maspin, p63 and p53 molecules might be beneficial in the management of patients with squamous cell carcinomas of the lung in the future.     

Correlation of p53 protein expression with apoptotic incidence in colorectal neoplasia

The wild-type p53 gene suppresses cell proliferation and induces apoptosis when it is transfected into human colon cancer cell lines. Therefore, mutation of the p53 gene, which correlates closely with p53 protein overexpression, would be predicted to activate cell proliferation and limit apoptosis. We tested this hypothesis by correlating p53 protein expression with cell proliferation and apoptosis in 70 neoplasms (29 adenomas and 41 carcinomas) using p53 and Ki-67 immunohistochemical staining and DNA nick end labelling. The p53 immunoreactivity was independent of the Ki-67 positivity. The apoptotic incidence was less frequent (P<0.005) in tumours with diffuse p53 protein overexpression than in those with the sporadic overexpression, defined as p53 staining of isolated or scattered expression. In addition, apoptotic incidence only correlated directly (P<0.05) with Ki-67 positivity in tumours with sporadic p53-protein expression. These results indicate that p53 protein that is expressed sporadically in colorectal neoplasms is probably wild-type protein and induces apoptosis in response to active cell proliferation. In contrast, diffusely overexpressed p53 protein in colorectal neoplasms is probably mutant and correlates with a reduction in apoptotic cell death independently of cell proliferation.     

Expression of p73 in normal skin and proliferative skin lesions

The p73 gene is a member of the p53 gene family and the structure and functions of p73 protein are similar to those of p53. However, these two proteins have different roles. In the present study, p73 protein was found immunohistochemically to be distributed in the basal cells of the epidermis, columnar basal cells in the hair follicle and peripheral cells without lipid droplets in the sebaceous and meibomian glands; it was expressed strongly in tumor cells in basal cell carcinomas and in the basal cell-like cells in seborrheic keratosis, and weakly or negatively in the squamous cell-like cells in seborrheic keratosis and in the tumor cells in squamous cell carcinomas. No relationship was detected between p73 and p53 protein distribution and between p73 protein expression and the proliferative potential, as shown by the Ki-67 immunopositive cell ratio. The present study shows that p73 protein is likely to play important roles in skin differentiation rather than proliferation or carcinogenesis of the skin.     

Apoptosis occurs independently of bcl-2 and p53 over-expression in non-small cell lung carcinoma

Certain oncogenes and tumour suppressor genes are known to modulate apoptosis. To investigate whether over-expressed bcl-2 and abnormally stabilized p53 are associated with reduced apoptosis in paraffin sections of non-small cell lung carcinoma, apoptotic, mitotic, and Ki-67 labelling indices were determined and correlated with bcl-2 and p53 immunoreactivity in 54 squamous cell carcinomas and 22 adenocarcinomas. Nineteen squamous cell carcinomas (35.2%) showed over-expression of bcl-2, but all 22 adenocarcinomas were bcl-2 negative. Thirty-seven squamous cell carcinomas (68.5%) and 13 adenocarcinomas (59.1%) showed p53 over-expression. Apoptotic tumour cells were identified among p53 positive and bcl-2 positive tumour cells. There was a significant linear correlation between apoptotic indices and mitotic indices. bcl-2 over-expression and p53 over-expression were not associated with attenuated apoptosis, or altered mitotic or Ki-67 labelling indices in either tumour type. Neither bcl-2 nor p53 was of prognostic significance. These results suggest that apoptosis in non-small cell lung carcinoma occurs independently, and is not modulated primarily by, bcl-2 or p53. It is likely that the effects on apoptosis of bcl-2 and p53 are countered by those of other oncogene products and/or additional factors that regulate apoptosis in vivo     

Expression of the cyclin dependent kinase inhibitor p21WAF1/CIP1 in oesophageal squamous cell carcinomas

 To elucidate the role of CDK inhibitor p21^WAF1/CIP1 in human oesophageal squamous cell carcinomas, we examined its expression immunohistochemically using surgically resected tissues from 25 patients, and have analyzed the relationship with alteration of p53 gene (F-SSCP analysis), proliferative activity (Ki-67 labelling index), frequency of apoptosis (in situ DNA nick end labelling), and degree of differentiation. P21 expression was observed in 11 cases (44%) with a percentage of positive cells ranging between 1% and 10%. Of the 25 cases, 4 cases showed >5% of positive cells. As for the relationship with p53 gene, all 7 p53-mutation positive cases were negative for p21 expression, whereas 11 out of 18 mutation negative cases showed positive for p21 expression. As for the relationship with degree of tumour differentiation, 6 out of 8 well differentiated type cases showed positive for p21 expression. By contrast, all 8 cases of poorly differentiated type were negative for p21 expression. Frequency of apoptotic cells was significantly higher in p21 positive cases than negative cases although Ki-67 labelling index was almost the same regardless of the expression of p21. P21 expressing cells were distributed mainly in the middle layers of the invading nests, especially around the keratinization, which was almost similar to the distribution of apoptotic cells. Our results suggest that expression of p21 in human oesophageal squamous cell carcinomas is induced by a p53-dependent pathway and affects apoptosis and differentiation of carcinoma cells. Received: 9 October 1996 / Accepted: 23 December 1996     

Expression of p53, p21 and bcl-2 in prognosis of lung carcinomas

Expression of suppressor genes 53 and bcl-2 as well as of protein p21 (partly induced by p53 gene) was analyzed in a group of 77 resection specimens and bronchial excision of lung carcinomas (of all basic histological types--squamous cell, neuroendocrine, adenocarcinoma, undifferentiated). Simultaneously the relation of tumor immunophenotype and level of differentiation, cell death and 2-year-survival of patients was evaluated. Gene p53 showed non-only an expected strong expression in squamous cell carcinomas but especially in adenocarcinomas, which were newly characterized by exceptional hyper-expression of p53 in lowly differentiated variants. Expression level of protein p21 and gene p53 was parallel only in adenocarcinomas and undifferentiated carcinomas but discordant in squamous cell and neuroendocrine carcinomas. Positivity of p21 slightly prevailed in well-differentiated variants of the histological types but an exceptional positivity was found even in all the undifferentiated carcinomas. Gene bcl-2 revealed a paradox of strong expression in lowly differentiated neuroendocrine and undifferentiated carcinomas. The level of bcl-2 expression in squamous cell carcinomas was found higher than in references. Among tumors with cell death there was an inverted relation of bcl-2 and p53 expression (high/low) in neuroendocrine carcinomas but both of them were mostly negative in squamous cell carcinomas. A more frequent 2-year-survival of squamous cell carcinomas was verified for bcl-2 positive tumors and newly for p53 positive squamous cell carcinomas. Evaluation of the expression of p53, p21 and bcl-2 in lung carcinomas is so equivocal that its prognostic usage was found to be only complementary to the direct immunohistochemical investigation of the growth activities.     

Expression of topoisomerase II alpha, Ki-67 and p53 in early stage laryngeal carcinomas not featuring vocal cord fixation

AIM: To determine whether topoisomerase II alpha (topoIIa) expression is an additional prognostic marker for less advanced stage laryngeal cancers first treated without surgery. Ki-67 and p53 protein levels were also assessed for comparison. EXPERIMENTAL DESIGN: Formalin-fixed, paraffin-embedded tumor material from 63 cases of squamous cell carcinoma (SCC) of the larynx (glottis, stages 0,1,2) was immunohistochemically stained for topoIIa, Ki-67 (MIB-1) and p53 (DO-7) and the results were compared with clinicopathologic findings. RESULTS: There were 7 stage 0 (TisN0M0), 33 stage I (T1N0M0), and 23 stage II (T2N0M0) SCCs with the TNM classification. Significant differences between carcinomas and normal mucosa were found for the topoIIa-LI, Ki-67-LI, and topoIIa-to-Ki-67 ratio. Regarding histologic grade, a significant difference in topoIIa-to-Ki-67 ratio was evident between well or moderately and poorly differentiated lesions. There were 19 cases of recurrence and 44 cases of nonrecurrence, but no significant differences were found for either of the indices or their ratio. No significant variation with p53 positivity was evident with reference to histologic differentiation, T-factor, clinical course, or proliferation. CONCLUSIONS: The results demonstrate that the topoIIa-to-Ki-67 ratio is a more sensitive parameter reflecting proliferation, for histologic grading of less advanced laryngeal SCCs, than topoIIa- or Ki-67-LIs.