Expression of p53 and p21 Protein in Transitional Mucosa Adjacent to Rectal Carcinoma and Its Clinical Implication

To study the biopathological characteristics of the transitional mucosa adjacent to rectal carcinoma, 34 cases were subjected to mucin histochemical and immunohistochemical study to observe the expression of p53 and p21 protein in distal mucosa adjacent to rectal carcinoma and its relationship to the mucin change. The expression of p53 protein was found in 29. 4 % (10/34) of distal transitional mucosa in the cytoplasm of goblet cells, and its positive staining was within 4 cm from carcinoma margin. A11 p53 positive mucosa was transitional mucosa. Overexpression of p21 protein was found in 26.5 % (9/34) of distal transitional mucosa in cytoplasm of crypt cells, and its positive staining was within 2 cm from carcinoma margin. There was no relationship between the expression of p53 and p21 protein in carcinoma and that in transitional mucosa ( P >0.05). These findings indicated that there was aberrant alteration of p53 and p21 genes in transitional mucosa adjacent to colorectal carcinoma, which provided further evidence that transitional mucosa was an unstable pre cancerous change. The aberrant mucin change and genetic alteration in distal mucosa of rectal cancer is within 4 cm.

HER2 gene status and the relationship with p21 protein expression in gastric cancer

Objective： We aimed to analysis the HER2 gene status and its relationship with p21 protein expression in gastric carcinoma. Methods： Fluorescence in situ hybridisation （FISH） and immunohistochemistry （IHC） techniques were used to detect HER2 gene status and p53 protein in 59 cases of gastric cancer. Results： FISH detection of HER2 gene amplification rate was 16.9% （10/59）, HER2 gene amplification in 49 cases without copy number gain and gene amplification were a total of 49.2% （29/59）. HER2 protein expression was 42.4% （25/59）, HER2 gene amplification rates in patients with ＋＋＋, ＋＋ HER2 protein expression were 3/3 and 5/8, while in patients with ＋ HER2 protein expression, it was 2/14, there was significant difference （P 0.05）. p21 protein expression rate was 49.2% （29/59）, HER2 gene amplification rates and p21 protein expression had significant difference in tumor invasion depth, lymph node metastasis （P 0.05）; had no statistical significance in histological type, age, gender differences （P 0.05）. Conclusion： HER2 gene amplification rate and gene copy number had positively correlation with p21 protein expression, HER2 gene status and expression of p21 protein combined detection can provide a reference value in gastric cancer metastasis, patient’s condition development and prognosis, it also can guide clinical development of individual treatment.

THE STUDY ON RELATIONSHIP BETWEEN CIGARETTE SMOKING AND THE p53 PROTEIN AND P21 PROTEIN EXPRESSION IN NON-SMALL LUNG CANCER

This paper discusses the relationship between cigarette smoking and the p53 protein and P21 protein expression by the immunohistochemical analysis in 93 cases with lung cancer in which squamous cell carcinoma accounted for 45 cases, adenocarcinoma 48 cases. The results showed that positive proportion of p53 protein expression was 74.20% (28 of 37 squamous cell carcinoma, 21 of 30 adenocarcinomas) in cigarette smoking group with lung cancers, and 38.46% (3 of 8 squamous cell carcinoma, 7 of 18 adenocarcinomas) in nonsmoking group with lung cancers. The difference was statistically significant. Odds ratio was 4.14 and confidence limits for OR was 1.42-12.52. A dose-related presents in the p53 protein expression for the smoking amount and smoking years. The positive proportion of P21 protein expression was 79.31% (21 of 28 squamous cell carcinoma, 25 of 30 adenocarcinomas) in cigarette smoking group with lung cancers, and 82.75% (10 of 11 squamous, 14 of 18 adenocarcinomas) in nonsmoking group with lung cancers, the difference was not statistically significant. But their positive proportion of P21 protein expression were very high in both groups. It was indicated that no relationship between cigarette smoking and the P21 protein expression. We suggest that the p53 gene could be a common target of tobacco-associated carcinogenesis in lung cancer.

Expression of p53 and p21 proteins in rat brain tissue after reperfusion following forebrain ischemia

Objective: To investigate the relationship between p53, p21 proteins and delayed neuronal death (DND) after reperfusion following forebrain ischemia in rats. Methods With four-vessel occlusion model of rats, the expression of p53, p21 proteins in brain tissue using labeled streptavindin-biotin immunohistochemical (LAAB) suming were observed. Re sults: The expression of p53, p21 proteins in brain was upregulated after reperfusion following 15 min forebrain ischemia and their distribution was similar. p53 and p21 proteins in brian sections was detected earlier in the white matter of hippocampal formation, thalamus, hypothalamus (6 h following reperfusion) than in the neuronal nuclei in cerebral cortex and CA1 region (24h), and the maximal induction was observed at 72 h following reperfusion. CA1 region suffered the most serious injury, where the positive expression of p53 and off proteins was most. Conclusion: Reperfusion following forebrain ischemia could upregulate the expression of p53 and p21 proteins in the brain region, suggesting that p53 and p21 proteins participate in and possibly promote the apoptosis of ’DND.

Immunohistochemical study on p53,H-rasp21,c-erbB-2 protein and PCNA expression in HCC tissues of Hart and minority ethnic patients

AIM To find out the difference of humanprimary liver carcinogenesis between Han andminority ethnic patients in Xinjiang.METHODS Expression of p53,c-erbB-2,H-rasp21 protein and proliferating cell nuclearantigen(PCNA)in tumor tissues of 50 patients(Han 38,minority 12)with primary hepaticcarcinoma was detected byimmunohistochemistry(LSAB).RESULTS The positive frequency of p53,c-erbB-2,H-rasp21 and PCNA expression was46.0%(23/50),70.0%(35/50),68.0%(34/50)and 82.0%(41/50)in tumor tissues;4.0%(2/50),22.0%(11/50),64.0%(32/50)and 52.0%(26/ 50)in peritumors respectively and asignificant difference,except for H-rasp21,ofoncogene alteration was found(P【0.05)between tumor and non-tumorous tissues.Combined the three oncogenes alteration,26%(13/50)tumor tissues had positiveimmunoreactivity,but in peritumor and normallivers it was negative.The positive rate of p53,c-erbB-2 and H-rasp21 protein expression was39.5%(15/38),60.5%(23/38)and 39.5%(15/38)in tumors of Han patients;66.7%(8/12),100%(12/12)and 75.0%(9/12)in minoritiesrespectively,with statistical difference (P【0.05).CONCLUSION Overexpression of p53,c-erbB-2and H-rasp21 in human primary liver carcinoma isan important biomarker of genetic alteration.The different frequency of these oncogeneticchanges may reflect some environmental or/andethnic hereditary factors affecting the livercarcinogenesis.The special life style of Han,Uygur,Kazak and Mongolia nationalities inXinjiang may also be related to theetiopathogenesis of this disease.

Effect of Boschniakia rossica on expression of GSTP,p53 and p21^(ras)proteins in early stage of chemical hepatocarcinogenesis and its anti-inflammatory activities in rats

AIM To investigate the effect of Boschniakiarossica（BR）extract on expression of GST-P,p53 and p21rasproteins in early stage of chemicalhepatocarcinogenesis in rats and its anti-inflammatory activities.METHODS The expression of tumor marker-placental form glutathione S-transferase（GST-P）,p53 and p21rasproteins were investigated byimmunohistochemical techniques and ABCmethod.Anti-inflammatory activities of BR werestudied by xylene and croton oil-induced mouseear edema,carrageenin,histamine and hotscald-induced rat pow edema,adjuvant-inducedrat arthritis and cotton pellet-induced mousegranuloma formation methods.RESULTS The 500 mg/kg of BR-H2O extractfractionated from BR-Methanol extract hadinhibitory effect on the formation of DEN-inducedGST-P-positive foci in rat liver（GST-P stainingwas 78% positive in DEN+AAF group vs 20%positive in DEN+AAF+BR group,P【0.05）andthe expression of mutant p53 and p21rasproteinwas lower than that of hepatic preneoplasticlesions（33% and 22% positive respectively inDEN+AAF group vs negative in DEN+AAF+BRgroup）.Both CH2Cl2 and H2O extracts from BRhad anti-inflamatory effect in xylene and crotonoil-induced mouse ear edema（inhibitory rateswere 26%-29% and 35%-59%,respectively）. BR-H2O extract exhibited inhibitory effect incarrageenin,histamine and hot scald-inducedhind paw edema and adjuvant-induced arthritis inrats and cotton pellet-induced granulomaformation in mice.CONCLUSION BR extract exhibited inhibitory effect on formation of preneoplastic hepatic foci in early stage of rat chemical hepato-carcinogenesis. Both CH2CI2 and H2O extracts from BR exerted anti-inflammatory effect in rats and mice.

Clinical significance of expression of p21 and p53 proteins and proliferating cell nuclear antigen in pancreatic cancer

Objective: To study the clinical significance and effect of p21, p53 protein as well as proliferating cell nuc- lear antigen (PCNA) on the occurrence and develop- ment of pancreatic carcinoma. Method: p21, p53 protein and PCNA expressions were detected in specimens from 30 patients with pancreatic carcinoma and 3 samples of normal pan- creatic tissue by immunohistochemistry. The data were analyzed together with clinical findings. Results: The positive expression rates of p21 and p53 proteins were 75.0% and 57.3% respectively in pan- creatic carcinoma, which were significantly different from those in the normal tissue (P<0.05). p21 and p53 proteins were positively correlated (P<0.05). The positive expression of PCNA was 43.33%± 17.99%, that was significantly higher than that in the normal pancreatic tissue (P<0.05). The expres- sion of PCNA was correlated with the histological grade (P<0.05). The positive expression rate was consistent with the exacerbation of cancer. The ex- pression was also correlated significantly with prog- nosis and p53 expression (P<0.05). Conclusions: The occurrence and development of pancreatic cancer are the result of associated function for many oncogenes and antioncogenes. PCNA may be helpful to identify malignant degree and prognosis of pancreatic cancer.

THE EXPRESSION AND CLINICAL SIGNIFICANCE OF P21(WAF1/CIP1) AND CYCLIN D1 PROTEIN IN COLORECTAL CARCINOMA

Objective To study the effect of P21(WAF1/CIP1) and cyclin D1 and their relationship in colorectal carcinoma.Methods The expression of P21 and cyclin D1 was studied in 40 colorectal carcinoma and 10 normal tissues using S P immunohistochemical technique.Results Decreased expression of P12 and overexpression of cyclin D1 were revealed in colorectal carcinoma.Decreased expression of P21 was related to lymph node metastasis.No correlation was found between cyclin D1 and clinicopathological parameters.Conclusion Decreased expression of P21 and overexpression of cyclin D1 may be involved in colorectal tumorigenesis,and were associated with poor prognosis.No correlation was found between P21 and cyclin D1 in colorectal carcinoma.

INHIBITION OF FARNESYL PROTEIN TRANSFERASE AND P21^(RAS) MEMEBRANE ASSOCIATION BY D-LIMONENE IN HUMAN PANCREAS TUMOR CELLS IN VITRO

The monoterpene d limonene inhibit the plasma membrane associated P21 ras expression and the posttranslational isoprenylation of P21 ras , a mechanism that may contribute to its efficacy in the chemoprevention and therapy of chemically induced rodent cancers and some human solid tumor cells. In the present study,the relative abilities of d limonene to inhibit membrane associated P21 ras expression in pancreas tumor cell(PaCa) was carried out with Western blotting, and the inhibition of farnesyl protein transferase (FTPase) activity during the Ras protein isoprenylation and cell proliferation were determined.Concomitantly,the effects of d limonene on P21 ras localization by immunohistochemistry and H ras oncogene expression in PaCa tumor cell line by Northern blotting were observed. The results showed that d limonene inhibited FPTase activity, thus to reduce P21H ras isoprenylation. d limonene could decrease P21 ras membrane association and increase cytosolic accumulation of P21 ras . This phenomenon was also noted when d limonene treated PaCa cells were stained immunohistochemically with anti P21 ras antibody. It is suggested that the inhibition of FPTase activity was closely related with the inhibiton of P21 ras membrane association and the alteration of P21 ras localization. Inhibition of farnesylation of P21 ras altered their intracellular localization and, hence, disrupted their biological activity,but no relationship with H ras oncogene expression was found.

Detection and Its Implication of Heat Stress Protein 27 and P21 in Nasopharyngeal Carcinoma

To study the expression of heat stress protein 27 (HSP27) and P21 in nasopharyngeal car- cinoma (NPC) tissue, and to evaluate the significance of both HSP27 and P21 in the pathogenesis, development and prognosis of NPC. Indirect immunofluorescence method combined with SABC was applied. Our results showed that (1) the positive rates of HSP27 and P21 expressed in NPC tissue in 36 cases were 88. 9 % and 94. 4%; (2) while in 10 hyperplastic nasopharyngitis tissues, the positive rate of HSP27 and P21 were both 5; (3) all the 5 normal tissues were negatively stained. It is obvi- ous that a co-expressing tendency of HSP27 and P21 could be identified, and it was associated with the degree of malignancy and the clinical stage of NPC. It is concluded that the positive expression of HSP27 and P21 may have clinical significance in the evaluation of the occurring, development and prognosis of NPC, and in NPC treatment.

P21^(ras)、P16在大肠癌中的表达及临床意义

目的探讨癌基因P21^(ras)及抑癌基因P16与大肠癌的关系。方法应用免疫组化SP法分析、研究了P21^(ras)蛋白、P16蛋白在80例大肠癌、20例大肠腺瘤及20例正常大肠组织中的表达。结果①P21^(ras)在前二者中的阳性表达率分别为70.1％(57/80)和65％(13/20),明显高于在正常组织中的30％(6/20),其比较具有显著性差异(x^2=17.66、P<0.005;x^2=5.23、P<0.05);P16在大肠癌中的阳性表达率为36.3％(29/80)低于在腺瘤及正常组织中的65％(13/20)和75％(15/20),其比较亦具有显著性差异。②P21^(ras)、P16的阳性表达率在大肠癌患者的年龄、性别及肿瘤大小方面无显著性差异,而与肿瘤的临床Dukes分期(x^2=6.20、P<0.025;x^2=6.25、P<0.05)、有无淋巴结转移及术后5a生存率密切相关。③P21^(ras)在不同的大肠癌组织病理类型中,其表达率无显著性差异;P16的阳性表达率随着肿瘤浸润深度的增加有下降趋势,但无统计学意义。④在80例大肠癌患者中,P21^(ras)阳性而P16阴性者比率高于其他三者,而且这类大肠癌患者的术后5a生存率下降。结论大肠癌的发生、发展,是由包括癌基因、抑癌基因在内的多种因素作用的结果;在临床工作中联合检测P21^(ras)及P16蛋白在大肠癌中的表达水平,对我们估计患者的病情、推测其预后有指导性意义。

贲门癌组织P53、P21和CD_(44V6)蛋白的表达及其意义

目的 探讨P53 、P2 1和CD44V6蛋白的表达情况与贲门癌生物学行为的关系。方法 采用免疫组化法对 4 1例贲门癌组织进行P53 、P2 1和CD44V6蛋白的测定。结果 贲门癌组织中P53 、P2 1和CD44V6蛋白的阳性率分别为 75 6 %、5 3 6 %和 4 1 4 % ,其表达与患者性别、年龄、临床分期和病理类型无明显关系。CD44V6蛋白阳性表达与肿瘤浸润深度有关 (P <0 0 5 ) ;P53 蛋白表达与P2 1蛋白表达呈正相关 ,但无统计学意义。P53 、P2 1和CD44V6蛋白阳性者预后比其阴性者差。结论 P53 、P2 1和CD44V6蛋白的测定可作为判断贲门癌患者预后的参考指标 。

Association of p53/p21 expression with cigarette smoking and prognosis in esophageal squamous cell carcinoma patients

【Abstract】factors,such as cigarette smoking,in esophageal squamous cell carcinoma(ESCC)in northeastern Iran,a region with a high incidence of ESCC.METHODS:The expression of p53 and p21 proteins was investigated immunohistochemically in tumor tissue from 80 ESCC patients and in 60 available paraffinembedded blocks of adjacent normal specimens from the cases,along with normal esophageal tissue from 80 healthy subjects.RESULTS:Positive expression of p53 protein was detected in 56.2%(45/80)of ESCC cases,and in none of the normal esophageal tissue of the control group(P【0.001).Furthermore,73.8%(59/80)of ESCC cases and 43.8%(35/80)of controls had positive expression of p21 protein(P【0.001).Cigarette smoking was significantly associated with p53 over-expression in ESCC cases(P=0.010,OR=3.64;95%CI:1.32-10.02).p21 over-expression was associated with poorer clinical outcome among the ESCC patients(P=0.009).CONCLUSION:Over-expression of p53 in association with cigarette smoking may play a critical role in ESCC carcinogenesis among this high-risk population of northeastern Iran.Furthermore,p21 over-expression was found to be associated with poor prognosis,specifically in the operable ESCC patients.

Expression of Survivin, CyclinD1, p21^(WAF1), Caspase-3 in Cervical Cancer and Its Relation with Prognosis

The implications of Survivin, CyclinD1, p21 WAF1, Caspase-3 in the development, progression and prognosis in cervical cancer were investigated. By using immunohistochemical SP method, the expression of Survivin, CyclinD1, p21 WAF1, Caspase-3 was detected in 41 cases of cervical cancer, 17 cases of cervical intraepithelial neoplasia (CIN) and 10 cases of normal tissues, and their relation with pathological grade, clinical stage, metastasis and survival time was analyzed. The results showed that the positive expression rate of Survivin, CyclinD1 in cervical cancer was significantly higher than in CIN group and normal control group (P<0.05). The median survival time in the patients with cervical cancer positive for Survivin and CyclinD1 was significantly shorter than in those with negative expression (P<0.05). The expression of both Survivin and CyclinD1 was not related with tumor grade, clinical stage and metastasis (P>0.05). The positive expression rate of p21 WAF1, Caspase-3 in cervical cancer was significantly lower than in CIN group and normal control group (P<0.05), and had a close relation with tumor grade (P<0.05). The expression of Survivin in cervical cancer in cervical cancer was negatively associated with that of Caspase-3 (P<0.01), but positively with that of CyclinD1 (P<0.01). Cox Multivariate analysis revealed that Survivin was the independent prognostic indicator influencing the survival time of the patients with cervical cancer (P<0.05). It was suggested that the high expression of Survivin or CyclinD1, and low expression of p21 WAF1 or Caspase-3 was closely correlated with the development of cervical cancer. Survivin and CyclinD1 could be used as a useful indicator to predict the prognosis of cervical cancer.

洛伐他汀对NB4细胞ras基因p21^(Ras)膜结合作用影响的体外试验

目的 :探讨洛伐他汀 (LOV)对人白血病NB4细胞的作用及其机制。方法 :以MTT比色法首先观察LOV对NB4细胞增殖的影响 ;利用逆转录 -聚合酶链反应半定量测定LOV作用于NB4细胞不同时间H -ras、K -ras、N -ras癌基因mRNA表达水平 ;同时采用流式细胞术测定NB4细胞p2 1Ras总蛋白、膜蛋白的表达。结果 :①LOV抑制NB4细胞增殖 ,IC5 0为 12 5 9μmol/L。②NB4细胞H、K、N -ras基因表达均为阳性。③LOV处理不同时间的NB4细胞H、K、N -ras基因转录水平无明显变化 ;p2 1Ras总蛋白水平也无变化 ,而细胞膜表面p2 1Ras蛋白水平随时间进行性下降。结论 :LOV抑制NB4细胞增殖。LOV靶向HMG -CoA还原酶 ,抑制p2 1Ras蛋白异戊二烯化、阻滞p2 1Ras蛋白与细胞膜结合 ;不影响ras癌基因以及p2 1Ras总蛋白的表达。

Clinical significance of immunohistochemica study of P53 protein in colorectal carcinoma

AIMS To determine the clinical significance of P53 protein ex-pression in colorectal carcinoma.METHODS The expression of P53 protein in 92 colorectal car-cinomas was examined using the monoclonal antibody PAb 1801.Correlation between P53 protein expression and prognosis in col-orectal carcinoma was analyzed using log-rank test.RESULTS The frequency of P53 protein expression was 57.61%,corresponding with Dukes’ staging.Analysis of survivordata demonstrated that the survival rate of colorectal carcinomawith positive P53 protein group was lower than that of negativeP53 protein group.CONCLUSIONS We conclude that the expression of P53 pro-tein is correlated with poor prognosis in colorectal carcinoma.

挥发性有机化合物对p53、rasp21、p16表达影响

目的探讨苯、甲醛混合物对NIH/3T3细胞中p53、rasp21、p16表达的影响。方法采用免疫组化法（SABC）观察甲醛、苯混合物致NIH/3T3细胞p53、rasp21、p16的表达情况。结果经苯、甲醛混合物处理后的第9～15d,p53、rasp21、p16表达阳性率分别为26%～45%,50%～60%,阳性率远远高于阴性对照组,差异有统计学意义（P〈0.01）;p16的阳性率为64%～40%,阳性率低于阴性对照组,差异有统计学意义（P〈0.01）。结论（VOCs）可使突变型的p53蛋白表达率增高;上调ras癌基因家族的表达产物rasp21;下调肿瘤抑制基因p16的表达。这可能是VOCs致癌的原因之一。

Expression of p27kip1, Rb protein and proliferating cell nuclear antigen and its relationship with clinicopathology in human pancreatic cancer

OBJECTIVE: To investigate the effect of inhibiting factor of cell cycle regulation p27kipl,retinoblastinoma protein （Rb protein）, and proliferating cell nuclear antigen （PCNA） on the genesis andprogression of human pancreatic cancer.METHODS: The expression of p27kipl, Rb protein and PCNA in the tumor tissue and adjacent tissue of32 patients with pancreatic cancer was detected by SP immunohistochemical technique.RESULTS: The p27kipl protein positive-expression rate in the tumor tissue of pancreatic cancer was56.25%, which was lower than that in the adjacent pancreatic tissue （P【0.05）. p27kipl proteinpositive-expression was correlated significantly with tumor cell differentiation and lymph node metastasis（P【0.05）. The Rb gene protein positive-expression rate in the tumor tissue was 50%, which was alsolower than that in the adjacent pancreatic tissue （P【0.05 ）. The PCNA positive-expression rate was71.87%, which was higher than that in the adjacent pancreatic tissue （P【0.05）. PCNA positive-expression was also correlated significantly with tumor cell differentiation and lymph node metastasis（P【0.05）.CONCLUSION: The decreased expression of p27kipl, Rb protein and over-expression of PCNA may playan important role in the genesis and progression of pancreatic cancer.

THE EXPRESSION AND SIGNIFICANCE OF P53 AND P21(WAF1/CIP1) IN THYROID CARCINOMA

Objective To determine the expression of P53 and P21 (WAF1/CIP1) in thyroid carcinomas and its relationship with development and prognosis of the carcinoma. Methods 90 cases of thyroid tissues (60 thyroid carcinomas, 10 thyroid adenomas, 10 goitres and 10 normal thyroid tissues) were studied by SP immunohistochemical method. Results Positive immunoreactivity of P53 and P21(WAF1/CIP1) was found only in thyroid carcinomas. The positive rate of the P53 and P21 is 53.3% and 41.7% respectively. The positive-staining rates of P53 were higher in cases of undifferentiated carcinomas, positive metastasis lymph nodes or in stage Ⅲ, Ⅳ than those in the cases of well-differentiated, no metastasis lymph nodes, or in stage Ⅰ,Ⅱ. In addition, the positive-staining of P21(WAF1/CIP1) were lower in cases of undifferentiated carcinomas, positive metastasis lymph nodes or stage Ⅲ, Ⅳ than that in the cases of well-differentiated, no metastasis lymph nodes or in stage Ⅰ,Ⅱ. The P21 (WAF1/CIP1) expression rate in the P53 positive group was lower than that in the P53 negative group (P<0.05). Conclusion The expression of P21(WAF1/CIP1) protein in thyroid cancer is related to P53-depend pathway and P53-independent pathway, mainly the P53-depend pathway. Examination of expression of P53 and P21 (WAF1/ CIP1) proteins may be helpful to judge the thyroid cancer's behavior and prognosis.

肺癌组织中P53和ras-P21癌基因蛋白的免疫组织化学研究

目的：为探讨肺癌组织中Ｐ＾５３和Ｐ６２１癌基因蛋白的表达及其临床意义。方法：应用免疫组化方法检测６９例肺癌组织标本中Ｐ＾５３和Ｐ＾２１癌基因蛋表达，结果采用卡方检验。结果：Ｐ＾５３和Ｐ＾２１在肺癌组织中的阳性表达率分别为４９．３％，６８．１％；肺癌癌旁支气管粘膜和腺体中的生表达率分别为０和１７．６％，与肿瘤区相比比较差异均非常显著。