Effect of HCV NS_3 protein on P53 protein expression in hepatocarcinogenesis

AIM To investigate hepatocarcinogenesis by detecting the effect of HCV NS 3 protein on P53 protein expression in hepatocellular carcinoma (HCC) and pericarcinomatous liver tissue (PCLT). METHODS The expression of HCV NS 3 and P53 protein was detected with immunohistochemical technique (SP method) in specimens of HCC and PCLT from 47 patients with negative HBV. RESULTS The positive rate of HCV NS 3 protein was lower in HCC (62%) than in PCLT (83%) ( P <0 025). The better differentiaton of cancer cells, the stronger expression of HCV NS 3 protein ( P <0 025). The positive rate of P53 protein in HCC (81%) was higher than in PCLT (47%) ( P <0 025). The worse differentiaton of cancer cells, the stronger expression of P53 protein ( P <0 05). The P53 protein expression was not correlated with the HCV NS 3 protein expression in HCC ( P >0 5), whereas their expression was closely related to PCLT ( P <0 01), and the expression rate of P53 protein in the cases of positive HCV NS 3 protein was higher than that in the cases of negative HCV NS 3 protein. CONCLUSION HCV NS 3 protein may exert its hepatocarcinogenic effect in early stage on host cells by endogenous pathway which may bring about mutation of p53 gene and transformation of hepatocytes.

Function of apoptosis and expression of the proteins Bcl-2,p53 and C-myc in the development of gastric cancer

INTRODUCTIONIn China ,the incidence and mortality of gastric cancer rank the second among all cancers. Recent development of cancer [1-20].The aim of this study was investigat the insight of apoptosis and bcl-2, p53 and C-myc protein expression in the development of gastric cancer .

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.

Changes of p53 protein blood level in esophageal cancer patients and normal subjects from a high incidence area in Henan,China

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Relationship between therapeutic efficacy of arterial infusion chemotherapy and expression of P-glycoprotein and p53 protein in advanced hepatocellular carcinoma

AIM： To investigate the relationship between the chemotherapeutic drug efficacy and the expression of P-glycoprotein （PGP） and p53 protein in advanced hepatocellular carcinoma （HCC）. METHODS： The study was conducted on 41 patients with advanced HCC who were treated by repeated arterial infusion chemotherapy. Biopsy specimens from the tumor were collected before the start of treatment in all the patients, and the specimens were stored frozen until immunohistochemical staining, which was performed after the start of treatment, to detect PGP and p53 protein expressions. Twenty of the fortyone patients were treated with an anthracycline drug （epirubicin hydrochloride; anthracycline group）, and the remaining 21 were treated with a non-anthracycline drug （mitoxantrone hydrochloride in 11 patients and carboplatin in 10 patients; non-anthracycline group）. The relationship between the chemotherapeutic efficacy and the results of immunostaining were compared between the two groups. RESULTS： Before the start of the treatment, PGPpositive rate was 90.2% （strongly-positive, 36.6%） and p53 protein-positive rate was 34.1% （strongly-positive, 19.5%）. In the anthracycline group, the response rate was 40.0%. The number of patients showing poor response to the treatment was significantly larger in the patients with strongly positive PGP expression （P= 0.005）, and their prognoses were poor （P= 0.001）. in the nonanthracycline group, the response rate was 42.9%,and there was no significant relationship between the chemotherapeutic drug efficacy and the PGP or p53 protein expression. When only the data from the 11 patients treated with anthraquinone drug, mitoxantrone, were analyzed, however, the number of patients who showed poor response to treatment was significantly higher among the p53-positive patients （P= 0.012）, irrespective of the survival outcome. CONCLUSION： The chemotherapeutic efficacy with an anthracycline drug for advanced HCC can be predicted by immunohistochemical analysis of PGP expression. Similarly, immunostaining to evaluate p53 protein may be useful to predict the response in patients treated with an anthraquinone drug.

Prognostic values of apoptosis-stimulating P53-binding protein 1 and 2 and their relationships with clinical characteristics of esophageal squamous cell carcinoma patients:a retrospective study

Background: Esophageal squamous cell carcinoma(ESCC) is a leading cause of cancer?related death, and new prognostic biomarkers are urgently needed. Apoptosis?stimulating P53?binding protein 1(ASPP1) and 2(ASPP2) have been reported to play important roles in the development, progression, metastasis, and prognosis of cancers, but their roles in ESCC have not been elucidated. In this study, we examined the expression of ASPP1 and ASPP2 in ESCC to evaluate their prognostic values.Methods: The protein expression of ASPP1, ASPP2, and P53 in 175 specimens of ESCC was detected using immuno?histochemical staining; their expression in cancerous and noncancerous tissues was scored according to the stain?ing intensity and the percentage of stained cells. The associations of ASPP1, ASPP2, and P53 with clinicopathologic parameters, overall survival(OS), and disease?free survival(DFS) were analyzed.Results: The protein expression levels of ASPP2 and P53 were significantly higher in cancerous tissues than in paired noncancerous tissues(P < 0.001), whereas the expression levels of ASPP1 in the two groups were similar. In ESCCs, ASPP1 expression was significantly associated with histological differentiation(P = 0.002) and invasive depth(P = 0.014); ASPP2 expression was associated with age(P = 0.029) and histological differentiation(P < 0.001); and P53 expression was associated with age(P and P53 expression. Survival an= 0.021) and tumor size(P alysis revealed that high AS= 0.040). No correlations were found between ASPP1, ASPP2,PP2 expression was significantly associated with increased 5?year OS(P = 0.001) and DFS rates(P ate of ESCC patients(= 0.010) and that high P53 expression was significantly associated with a reduced 5?year DFS rP atio(HR): 0.541, 9= 0.015). Multivariate Cox analysis indicated that ASPP2 was an inde?pendent predictor of OS [hazard r5% confidence interval(CI) 0.363–0.804] and DFS(HR: 0.599, 95% CI 0.404–0.888) of ESCC patients and that P53 was an independent predictor of DFS(HR: 2.161, 95% CI 1.100–4.245).Conclusions: ASPP1 might be involved in the progression of ESCC, and ASPP2 was a potential prognostic biomarker of ESCC and should be evaluated in future studies.

Role of microRNA-21 in uveal melanoma cell invasion and metastasis by regulating p53 and its downstream protein

AIM： To reveal the insight mechanism of liver metastasis in uveal melanoma, we investigated cell functions of microRNA-21 in three different uveal melanoma cell lines and analyze the relationship of target gene p53 and its downstream targets which been found significant expression in our previous study.METHODS： Quantitative real-time polymerase chain reaction （qRT-PCR） was used to detect microRNA-21 expression in normal uveal tissue and uveal melanoma cell lines. Lenti-virus expression system was used to construct OCM-1, MuM-2B and M619 cell line with stable overexpression and inhibition of microRNA-21. In vitro cell function tests such as cell proliferation, cell apoptosis, cell circle and abilities of migration and invasion were examined by MTT, BrdU assay, flow cytometry, transwell assay and Matrigel invasion assay respectively. The target gene was predicted by bioinformatics and confirmed by using a dual luciferase reporter assay. The expression of p53 and its suspected downstream targets LIM and SH3 protein 1 （LASP1） and Glutathione S Transferase pi （GST-Pi） were determined by qRT-PCR in mRNA level and western blotting analysis in protein level. Finally, the effect of microRNA-21 in a xenograft tumor model was assessed in four-week-old BALB/c nude mice. RESULTS： Compared to normal uveal melanoma, expressions of microRNA-21 were significantly higher in uveal melanoma cell lines. Overexpression of microRNA-21 promoted proliferation, migration, and invasion of OCM-1, M619 and MuM-2B cells, while inhibition of microRNA-21 reveal opposite effects. Wild type p53 was identified as a target gene of microRNA-21-3p, and proved by dual luciferase reporter assay. Up-regulated microRNA-21 inhibited the expression of wild type p53 gene, and the increased expression of LASP1 in mRNA level and protein level, while down-regulated microRNA-21 presented opposite way. However, GST-pi showed the potential pattern as expected, but relative mRNA level showed no statistically significant difference in OCM-1 cells. Furthermore, the mRNA expression of GST-pi was decreased in microRNA-21 overexpressing MuM-2B, and increased in M619 cells with inhibition of microRNA-21. In vivo, inhibition of microRNA-21 reduced tumor growth with statistically significant difference.CONCLUSION： These findings provide novel insight into molecular etiology of microRNA-21 in uveal melanoma cell lines, and suggest that microRNA-21 might be a potential candidate for the diagnosis and prognostic factor of human uveal melanoma in future.

DNA PLOIDY，EXPRESSION OF p53 PROTEIN AND METASTATIC BEHAVIOUR OF GASTRIC CARCINOMA

DNA ploidy of 57 gastric carcinomas with metastases(12 liver,1 adrenal,4 ovary and 48 lymph node) were measured by flow cytometry.DNA anueploidy was significantly related to liver metastases:9 out of 12 gastric carcinomas with liver metastases were anueploid(75%) as compared to 13 out of 45(28.8%) of cases without liver metastases(P<0.01);the one gastric carcinoma with adrenal metastasis was also anueploid.DNA ploidy was not related to ovarian or lymph node metastases.Another interesting finding was that all of 3 gastric carcinomas with liver metastases which showed a diploid DNA pattern,expressed p53 protein, while all of 3 carcinomas with liver metastases but no p53 protein expression were anueploid.The expression of p53 protein was not related to ovarian metastases.The results suggested that an anueploid DNA pattern and the expression of p53 protein are both objective markers valuable in predicting high risk potential of metastases to the liver,and that the combined detection of these markers can be a most useful method in the follow-up of Patients with gastric carcinoma in detecting those at high risk of developing metastases following surgical resection.Also the poorer prognosis of Patients with gastric carcinoma showing an anueploid DNA pattern may be related to the development of distant organ metastases through the blood vascular system.Furthermore,the clone of gastric carcinoma cells which accumulate p53protein or show an anueploid DNA pattern may have a causative role in the development of liver(&.adrenal) metastases.

Killing of p53-deficient hepatoma cells by parvovirus H-1 and chemotherapeutics requires promyelocytic leukemia protein

AIM: To evaluate the synergistic targeting and killing of human hepatocellular carcinoma (HCC) cells lacking p53 by the oncolytic autonomous parvovirus (PV) H-1 and chemotherapeutic agents and its dependence on functional promyelocytic leukemia protein (PML). METHODS: The role of p53 and PML in regulating cy-totoxicity and gene transfer mediated by wild-type (wt) PV H-1 were explored in two pairs of isogenic human hepatoma cell lines with different p53 status. Further-more,H-1 PV infection was combined with cytostatic drug treatment. RESULTS: While the HCC cells with different p53 status studied were all susceptible to H-1 PV-induced apoptosis,the cytotoxicity of H-1 PV was morepronounced in p53-negative than in p53-positive cells. Apoptosis rates in p53-negative cell lines treated by genotoxic drugs were further enhanced by a treatment with H-1 PV. In flow cytometric analyses,H-1 PV infection resulted in a reduction of the mitochondrial transmembrane potential. In addition,H-1 PV cells showed a significant increase in PML expression. Knocking down PML expression resulted in a striking reduction of the level of H-1 PV infected tumor cell death. CONCLUSION: H-1 PV is a suitable agent to circumvent the resistance of p53-negative HCC cells to genotoxic agents,and it enhances the apoptotic process which is dependent on functional PML. Thus,H-1 PV and its oncolytic vector derivatives may be considered as therapeutic options for HCC,particularly for p53-negative tumors.

cyclin E、p53、CD44s、CD44v6与早期乳腺癌的相关性及预后预测分析

目的分析肿瘤组织的细胞周期素E(cyclin E)和p53、CD44s、CD44v6蛋白与早期乳腺癌的相关性及预后预测价值。方法选取2018年7月—2020年7月喀什地区第二人民医院收治的80例临床分期为Ⅰ~Ⅱ期的早期乳腺癌患者进行回顾性分析,将其分为恶性组;另选取同期喀什地区第二人民医院收治的80例通过病理学检验确诊为良性乳腺肿瘤患者,将其分为良性组。分别对两组患者留存的肿瘤组织进行免疫组化检测,检测cyclin E、p53、CD44s、CD44v6表达,并对比上述指标的阳性率,应用Spearman相关分析方法分析cyclin E、p53、CD44s、CD44v6与早期乳腺癌的相关性。所有患者均采取手术治疗,随后对80例早期乳腺癌患者进行3年随访,依照随访结果将患者分为2个亚组,即预后不良组(n=25)和预后良好组(n=55),对比两组患者一般临床特征及cyclin E、p53、CD44s、CD44v6阳性率,并应用Logistic回归分析cyclin E、p53、CD44s、CD44v6对早期乳腺癌预后的预测价值。结果恶性组患者cyclin E、p53、CD44s、CD44v6阳性率分别为42.50%、61.25%、77.50%、81.25%,明显高于良性组1.25%、5.00%、10.00%、12.50%(P<0.05);Spearman相关分析结果显示:cyclin E、p53、CD44s、CD44v6与早期乳腺癌呈正相关(P<0.05);预后良好组与预后不良组患者绝经情况、年龄、病理类型、治疗方式、三阴性乳腺癌、肿瘤大小、组织分化程度对比,差异无统计学意义(P>0.05),预后良好组与预后不良组患者临床分期、cyclin E、p53、CD44s、CD44v6阳性例数对比,差异有统计学意义(P<0.05);Logistic回归分析结果表明:cyclin E、p53、CD44s、CD44v6阳性表达为影响早期乳腺癌预后的独立影响因素(P<0.05)。结论cyclin E、p53、CD44s、CD44v6表达水平与乳腺癌的发生、发展具有明显关系,且上述指标呈阳性表达为早期乳腺癌预后不良的独立预测因素。

Human papillomavirus and p53 protein immunoreactivity in condylomata acuminatum and squamous cell carcinoma of penis

Aim: To determine the immunoreactive pattern of human papillomavirus (HPV) antigen and p53 protein in condylo-mata acuminatum (CA) and squamous cell carcinoma (SCC) of penis. Methods: Immunohistochemistry for HPVand p53 were performed in 40 specimens of formalin fixed, paraffin embedded tissues using a polyclonal (rabbit) anti-body against HPV and a monoclonal (mouse) antibody against human p53 protein. Twenty one cases of CA and nine-teen cases of SCC were examined. Results: HPV antigen was detected in all 21 CA and 2 penile SCC. p53 proteinoverexpression was observed in 12 of 19 (63%) SCC in which 6 cases were strong positive. Five of 21 CA (24%)showed low-grade p53 protein overexpression. Conclusion; CA is related to HPV infection and some cases showp53 protein low-grade overexpression. In contrast, p53 protein overexpression is common in penile SCC, which is sel-dom related to HPV infection. (Asian J Androl 2001 Mar; 3: 75-77)

p53 MUTATIONS AND PROTEIN OVEREXPRESSION IN PRIMARY COLORECTAL CANCER AND ITS LIVER METASTASIS

Objective: To compare p53 status in primary and hepatic metastatic colorectal cancer in 34 patients. Methods: p53 gene status (exons 5–9) was examined by PCR, denaturing gradient gel electrophoresis (DGGE) and automated sequencing. P53 protein was detected by immunohistochemistry using monoclonal antibody DO-7. Results: p53 mutations were found in exons 5 through 9 in 21 of 34 patients (61.8%). Among them, 5 patients had mutation in liver metastasis but not in their primary tumors while in the other patients the same mutations were found in both primary and metastatic colorectal cancers. In no patients was p53 mutation exclusively found in the primary colorectal tumors. Moreover, additional mutation was detected in the metastatic lesions in two cases. Of the 37 mutations within the exons examined, 73% was missense mutation and 16% was nonsense mutation. There were 4 microinsertions. p53 protein was overexpressed in both primary and metastatic colorectal cancers with p53 gene mutations. The presence of p53 mutation significantly correlated with p53 protein accumulation (r=0.96,P<0.001). However, in 4 patients with p53 nonsense mutation, immunohistochemical staining was negative. In three patients who showed no p53 mutation of the primary tumor, p53 protein was consistently overexpressed. Conclusion: In colorectal cancers, p53 gene mutation usually appears first in the primary tumor and maintains as such but is more prominent when metastasized to the liver. However, p53 gene mutation may occur only after being metastasized. Although p53 gene mutation and p53 protein overexpression correlate with each other, either parameter examined alone may lead to false positive or negative results.

Association between HPV16/18 Infection and Expression of P53 protein in Laryngeal Papillomas

To understand the relationship between expression of P53 protein and HPV16/18 infection in laryngeal papillomas, PCR and immunohistochemical tech-niques were used to examine the paraffin-embedded tissue samples of laryngeal pa-pillomas from 35 subjects. HPV 16/18-DNA was found in 24 cases of laryngeal papillomas (68. 8 %). Overexpression of P53 protein was detected in 19 cases (54. 3 % ). Both HPV16/18-DNA and overexpression of P53 protein were demon-strated in 12 cases of laryngeal papillomas (34. 3 % ). Our results suggest that HPV16/l8 infection and P53 gene mutation are associated with pathogenesis of la-ryngeal papillomas. The relation between HPV infection and P53 mutation in tis-sues of laryngeal papillomas remains to be clarified.

ASSOCIATION OF EXPRESSION OF P53 PROTEIN WITH CELL PROLIFERATIVE ACTIVITY AND PROGNOSIS IN COLORECTAL CANCER

The expression of p53 protein in 66 cases ofcolorectal cancer and its relationship to cell porliferativeactivity, lymph node metastasis as well as prognosis wereinvestigated by means of AB-PAP immunohistochcmicaltechnique- The results showed that 62.1/o of colorectalcancer was positive of p53 expression. The cellproliferative activity and the frequency of lymph nodemetastasis in p53- positive tumors were significantlyhigher than those in p53-negative tumors (P<0.05). Thesurvival rate in patients with p53- positive tumors wassignificantly poorer than those with p53- negative tumors(P<0.05). Our results suggest that the abnormalexpression of p53 and cell proliferation associated withmutations are involved in both human carcinogenesis andlymph node metastasis of colorectal cancer. Examinationof p53 expression is of value in understanding the degreeof malignancy, and evaluating prognosis of the disease.

Expression of the chemoresistance-related proteins and p53 gene as a predictor of chemotherapy response and a prognostic factor in patients with ovarian cancer at the stages of II-IV

Objective To clarify the prognostic significance of histologic subtype and its correlation to expression of chemoresistance-related proteins （CRPs） in ovarian cancer. Methods A total of 107 stage II-IV ovarian cancers, where the proportion of serous, endometrioid, mucinous, and clear cell subtype was 62.6%, 15.9%, 14.0%, and 7.5%, respectively, were investigated for glutathione Stransferase-pi （GST-pi）, MDR （multidrug resistance）-l, and p53 expression using immunohistochemistry. Results GST-pi expression was detected in 62.6% of the tumors and was not related to histologic subtype of tumor. MDR-1 expression was observed in 52.3% of the tumors tested and was more frequently detected in serous adenocarcinomas than other histologic subtypes of tumor （P〈0.001）. P53 expression was found in 43.3% of serous, 35.3% of endometrioid, 40.0% of mucinous adenocarcinomas and 37.5% of clear cell adenocarcinomas. In univariate analysis, there are direct correlations between CRPs and overall survival. In multivariate analysis, GST-pi expression （P=0.0052）, MDR-1 expression （P=0.0058）, histologic subtype （P=0.0067）, FIGO stage （P=0.0089）, and residual tumor （P=0.0041） were found to be significant independent prognostic factors. Conclusion Histologic subtype proved to be the significant independent prognostic factor in addition to FlGO stage and residual tumor in stage II-IV ovarian cancer. GST-pi, MDR-1, and p53 expression pattern is closely related to histologic subtype of ovarian cancer, at the same time they are the significant predictors of survival.

P53 protein expression and cell viability in irradiated peripheral blood mononuclear cells as bioindicators of radiosensitivity

Cellular radiosensitivity is directly correlated with the mechanism of DNA repair, in which p53 protein plays a major role. In this context, this study correlated cell death with p53 expression in lymphocytes irradiated in vitro with different doses of gammaradiation. For this, peripheral blood samples were collected from 10 healthy subjects. Each sample was divided in aliquots and, separately, irradiated with doses of 0,5;2 and 4 Gy. After this, peripheral blood mononuclear cells (PBMCs) were isolated and cultivated during 72 hours in 5% CO2 at 37oC without mitogen stimulation. The expression of p53 protein was evaluated by flow cytometry. In parallel, cell viability was determined by trypan blue staining. Statistical analysis was performed us-ing analysis of variance (ANOVA), differences were considered as statistically significant when p < 0.05. The results showed an increase of p53 expression with the absorbed dose, which was proportional to cell death, suggesting that p53 can be used as bioindicator of individual radiosensitivity.

THE QUANTITATIVE MEASUREMENT OF BCL-2, P53 PROTEIN AND PCNA EXPRESSION IN BREAST CARCINOMA AND THEIR CORRELATION WITH PROGNOSIS

To study quantitative index of bci-2, P53, Nroliferating cell nuclear antigen (PCNA),ER and PR in breast carcinoma and their correiation and their relatiousbip with prognosis, the ex expression of bcl-2, P53 and PCNA were studied by immunohistochemical technique. The measurementof ER and PR used enzyme linked affinuity histochemical methods. The quantitative index was analyzed by image technique. All analyses were hased on 60 breast carcinomas. The results were as follows:the more bcl-2 protein, the lower histological graded the longer survival term and the highersurvival rate (P< 0. 05). The quautitative measurement of bcl-2, P53 and PCNA expression were ofvalue in evaluating the degree of differentiation and prognosis in breast carcinoma. The quantitativeand qualitative measurement or p53 protein expression showed a Ⅰwerful evidence in evaluatingprognosis of bcl-2 were more significant in evaluating poor prognosis of breast carcinoma. A relationship between bcl-2 and ER, PR showed a better value for response to endocrine therapy in breastcarcinoma patients.

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 。

p53、bcl-2和CD44v6蛋白表达与乳腺癌转移的相关性研究

目的探讨乳腺癌及癌旁正常乳腺组织中p53、bcl2和CD44v6蛋白的表达及意义。方法采用免疫组化法检测96例乳腺癌及其癌旁正常乳腺组织中p53、bcl2和CD44v6蛋白的表达,并分析其与淋巴结转移和cerbB2表达状态的相关性,从而评价这些指标在预测乳腺癌转移方面的价值。结果正常乳腺组织中p53蛋白为阴性,在乳腺癌中阳性表达率为65.63%;随着组织学分级的增高,阳性率逐渐增高;淋巴结转移组阳性表达率明显高于无淋巴结转移组,并与cerbB2表达状态呈正相关。乳腺癌组织中bcl2阳性表达率明显低于周围正常乳腺组织,随着组织学分级的增高,阳性率逐渐降低,淋巴结转移组中的表达率明显低于淋巴结非转移组,与cerbB2的表达呈负相关。CD44v6在乳腺癌组织中的阳性表达率明显高于正常乳腺组织,随着组织学分期的增加,CD44v6的阳性表达率亦增高,但差异无显著性,淋巴结转移组的阳性率略高于无淋巴结转移组,差异也无显著性,与cerbB2表达无相关性。结论p53和bcl2蛋白可作为预测乳腺癌转移的指标,CD44v6的阳性表达可能与乳腺癌的发生、进展有一定关系,但尚不能把它作为预测乳腺癌转移的稳定的生物学指标。

粘附分子CD44v6和p53基因在乳腺癌组织中的表达及其与DNA倍体的关系

背景与目的:细胞表面粘附分子CD44的变构体CD44v6在肿瘤转移中起重要作用,但对其在乳腺癌中的表达研究结果差异较大。p53基因突变是最常见的与人类肿瘤发生相关的基因异常。本研究探讨CD44v6和p53基因及DNA倍体在乳腺癌中的表达意义与相互关系。方法:采用流式细胞光度术(FCM)定量分析了52例原发性乳腺癌组织、相应癌旁组织和18例乳腺良性肿瘤中P53和CD44v6及DNA倍体的变化状况。结果:乳腺癌组织中P53、CD44v6蛋白表达及S期比例(SPF)和增殖指数(PI)显著高于相应癌旁组织、乳腺良性肿瘤和正常乳腺组织(P<0.05)。P53、CD44v6、SPF、PI在不同年龄、不同病理类型、不同肿瘤大小和临床分期间的表达差异均无显著意义(P>0.05)。有淋巴结转移组患者P53、CD44v6表达和SPF、PI值明显高于无淋巴结转移组患者(P<0.05)。52例乳腺癌中异倍体23例(44.23%),20例发生转移;二倍体29例,17例发生转移,异倍体乳腺癌患者淋巴结转移率明显高于二倍体乳腺癌患者(P<0.05),且异倍体乳腺癌患者P53蛋白表达明显高于二倍体乳腺癌患者(P<0.05),而CD44v6表达在两者间未见显著差异(P>0.05)。相关分析显示,癌组织P53蛋白表达与SPF和PI具显著正相关性(P<0.01),而CD44V6与SPF和PI均无关(P>0.05)。结论:P53、CD44v6蛋白表达和DNA含量在乳腺癌?