恶性黑色素瘤中C-erbB-2、P53、P16蛋白的表达

目的:探讨恶性黑色素瘤中C蛳erbB蛳2、p53、p16蛋白的表达及其相互关系。方法:应用免疫组化S蛳P法对14例恶性黑色素瘤和39例色素痣组织中C蛳erbB蛳2、p53、p16蛋白表达进行检测。结果:14例恶性黑色素瘤中C蛳erbB蛳2、p53和p16蛋白的阳性率分别为50 %(7/14)、64 %(9/14)、43 %(6/14)。39例色素痣中C蛳erbB蛳2、p53和p16蛋白的阳性率分别为18 %(7/39)、36 %(14/39)、77 %(30/39)。C蛳erbB蛳2、p53、p16蛋白阳性率与恶性黑色素瘤的发生有密切的关系(P < 0.05)。结论:肿瘤多基因分析比单基因分析有价值。癌基因C蛳erbB蛳2和抑癌基因p53、p16蛋白的表达异常及协同作用在恶性黑色素瘤的发生发展中起重要作用。     

Dietary lutein inhibits mouse mammary tumor growth by regulating angiogenesis and apoptosis

Even though we previously reported that dietary lutein can inhibit mammary tumor growth, the mechanism of this action was unknown. Here, we studied the action of dietary lutein through its possible regulation of apoptosis and angiogenesis. Female BALB/c mice were fed a semi-purified diet containing 0 (control), 0.002 or 0.02% lutein (n = 20/treatment) for 2 weeks prior to inoculation with 100,000 -SA mouse mammary tumor cells into the right mammary fat pad. Tumor volume was measured daily until day 50 postinoculation when all mice were killed. Angiogenesis and apoptosis activities in the tumors were measured by immunohistochemistry. Apoptosis and necrosis of blood lymphocytes were quantitated by flow cytometry using Annexin V-FITC and propidium iodide staining. The expression of the p53, Bax and Bcl-2 mRNA was measured by RT-PCR amplification. Lutein was not detectable in the plasma, liver or tumor of unsupplemented mice, but increased in a dose-dependent manner in lutein-supplemented mice. Mice fed lutein had tumors that were 30 to 40% smaller (p < 0.05) on day 50 post-inoculation compared to unsupplemented mice. Final tumor volume was lowest in mice fed 0.002% lutein. Mice fed lutein had higher apoptotic activity in the tumors but lower apoptotic activity in blood lymphocytes as compared to unsupplemented animals. These observations were supported by the observed increase in the expression of the proapoptotic genes, p53 and Bax, together with a decrease in the expression of the antiapoptotic gene, Bcl-2, and consequently an increase in the Bax:Bcl-2 ratio in tumors from lutein-fed mice. Furthermore, lutein-fed mice also had lower (p < 0.05) angiogenic activity in the tumors as compared to unsupplemented mice. The greatest beneficial effect on apoptosis and angiogenesis was observed with mice fed 0.002% lutein. Therefore, dietary lutein, especially at 0.002%, inhibited tumor growth by selectively modulating apoptosis, and by inhibiting angiogenesis.     

Enhanced tumorigenesis in p53 knockout mice exposed in utero to high-dose vitamin E

The limited antioxidative capacity of the embryo and fetus may increase their risk for cancer initiation and/or promotion by reactive oxygen species (ROS)-mediated oxidative DNA damage and/or signaling. To determine if cancer can originate in utero, a high dietary dose of the antioxidant vitamin E (VE) (10% dl-alpha-tocopherol-acetate) was given to cancer-prone p53 knockout mice throughout pregnancy. Although reducing fetal death (P < 0.05), in utero exposure to VE enhanced postnatal tumorigenesis in both +/- (P < 0.04) and -/- (P < 0.0008) p53-deficient offspring. VE did not alter maternal weights, offspring p53 genotypic distribution or tumor spectrum. Constitutive embryonic DNA oxidation in untreated -/- p53 embryos [gestational day (GD) 13] was higher than in +/- and +/+ p53 littermates (P < 0.05). VE reduced DNA oxidation in -/- p53 embryos (P < 0.05) without affecting +/- and +/+ p53 littermates. VE had contrasting, tissue-dependent effects on fetal (GD 19) DNA oxidation, with reductions in -/- and +/- p53-deficient fetal brains (P < 0.01), increases in skin (P < 0.05) and no effect in liver and thymus. The 250-fold increase in dietary VE levels produced only 1.6-6.3-fold, tissue-dependent increases in tissue concentrations. The greatest increase, in fetal skin, correlated with increased DNA oxidation in that tissue in -/- and +/- p53-deficient fetuses and enhanced tumorigenesis in these genotypes. These results show that some cancers may originate in utero and the risk can be enhanced by embryonic and fetal exposure to high dietary levels of VE. The elevated DNA oxidation in some tissues of untreated -/- p53 offspring suggests that ROS may contribute to their higher baseline tumor incidence. The limited and tissue-dependent disposition of VE indicates substantial conceptal regulation. The similarly selective and contrasting effects of VE on DNA oxidation may contribute to its controversial protective efficacy and suggest that its effects on tumorigenesis are cell-specific, possibly in high doses involving a pro-oxidative mechanism.     

A mouse model for tumor progression of lung cancer in ras and p53 transgenic mice

Although ras and p53 are the most commonly found oncogene and tumor suppressor gene, respectively, in human cancers, their collective roles in tumor progression have yet to be defined in animal models. Here, we demonstrated the synergistic effect between ras and p53 in promoting tumor progression during lung tumorigenesis using bitransgenic mice. Mice with a heterozygous knockout of K-ras (K-ras(wt/ko)) were mated to p53 transgenic mice (p53(val135/wt)) in lung tumorigenesis (K-ras(wt/ko) x p53(val135/wt)). F(1) mice exhibited a significant increase in lung tumor load (tumor multiplicity x tumor volume) when compared to those seen in either K-ras(wt/ko) mice or p53(val135/wt) mice alone. Furthermore, over 50% of the lung tumors were lung adenocarcinomas in bitransgenic mice compared to only 3% in wild-type mice. Alterations of ras and p53 appear to promote the development of lung adenocarcinomas. These results provide the in vivo experimental evidence of synergistic interactions of ras and p53 in lung tumor progression.     

DNA sequence copy number changes in gastrointestinal stromal tumors: tumor progression and prognostic significance

To identify genetic changes related to tumor progression and find out diagnostic and prognostic genetic markers in gastrointestinal stromal tumors (GISTs), 95 tumor samples (24 benign GISTs, 36 malignant primary GISTs, and 35 GIST-metastases) from 60 patients were studied using comparative genomic hybridization. DNA copy number changes were detected in all samples. Benign GISTs had a mean of 2.6 aberrations/ sample (losses:gains, 5:1) and significantly fewer DNA copy number changes and fewer gains than malignant primary and metastatic GISTs (P < 0.01). High-level amplifications were not seen in benign GISTs. Malignant primary GISTs had a mean of 7.5 aberrations/tumor (losses: gains, 1.6:1), whereas the mean number of aberrations/metastatic GIST was 9 (losses:gains, 1.8:1). Frequent changes observed in all GIST groups included losses in chromosome arms 1p (51%), 14q (74%), and 22q (53%). Gains and high-level amplifications at 8q and 17q were significantly more frequent in metastatic GISTs (57 and 43%) than in benign GISTs (8 and 0%; P < 0.001) and malignant primary GISTs (33 and 25%; P < 0.05). Gains and high-level amplifications at 20q were only seen in malignant primary and metastatic GISTs (P < 0.01), and gains at 5p were not detected in benign GISTs (P < 0.01). Losses in chromosome arm 9p were never seen in benign tumors (P < 0.001), and they were more frequent in metastatic GISTs than in malignant primary GISTs (63 and 36%; P < 0.05). Losses in 13q were less frequent in benign GISTs than in malignant primary (P < 0.05) and metastatic (P < 0.01) GISTs. Our results show that several DNA copy number changes are related to the behavior of GISTs and can be used as prognostic markers for tumor progression.     

The amplifier effect: how Pin1 empowers mutant p53

Mutation of p53 occurs in 15 to 20% of all breast cancers, and with higher frequency in estrogen-receptor negative and high-grade tumors. Certain p53 mutations contribute to malignant transformation not only through loss of wild-type p53 but also through a gain of function of specific p53 mutations. How these hotspot mutations turn p53 from a tumor suppressor into an oncogene had until now remained incompletely understood. In an elegant paper published in the July 12 issue of Cancer Cell, Girardini and colleagues show how Pin1-mediated prolylisomerization, a regulatory mechanism intended by evolution to support p53's function as a guardian of the genome, can go haywire and accelerate malignant transformation when p53 carries a dominant-negative mutation.     

Ras and p53 expression in non-small-cell lung-cancer patients - p53 over-expression correlates with a poor prognosis

Expression of the tumor suppressor gene p53 and the ras oncogene were examined in 46 tumor and nodal specimens of non-small cell lung cancer (NSCLC) using the antibodies p53 pAb 240 and ras Y13-259 respectively. p53 expression was elevated in 46% and ras p21 was over-expressed in 85% of the tumor specimens analyzed. Fifteen cases of benign lessions were also assessed for both ras p21 and p53 expression; all were found to have negative staining. p53 over-expression was found to correlate with a poor prognosis in both the tumor specimens (p<0.05) and in the nodal tissues (p<0.005). Ras p21 over-expression was found to be associated with survival (p<0.1) in both the tumor and the nodal specimens. Stage of the disease correlated with survival; similarly both p53 and ras p21 over-expression correlated with stage. No correlations were found with the pathological grade of the tumors nor with a history of smoking or duration of smoking. No K-ras mutations at codon 12 were observed in a further 15 NSCLC specimens analyzed. These results indicate that the p53 gene in particular plays a role in the stages of NSCLC.     

血清MMP-2、P53抗体检测在非小细胞肺癌患者病情判断中的临床价值及意义

目的 探讨血清MMP-2、P53抗体检测在非小细胞肺癌患者病情判断中的临床价值及意义.方法 回顾性分析80例非小细胞肺癌患者临床医学资料,选取同期80例肺部疾病良性患者作为良性组,另取80例健康人士作为对照组,对比各组血清MMP-2和P53相关检测指标.结果 3组MMP-2和P53抗体表达量对比,差异显著(P<0.05...     

上颌窦恶性肿瘤组织中p53和PCNA的表达及其意义

背景与目的：据文献报道,p53和增殖细胞核抗原（proliferating cell nuclear antigen,PCNA)与恶性肿瘤的发生发展有密切关系,本研究检测p53和PCNA在上颌窦恶性肿瘤、良性肿瘤和炎症性病变中表达的强度差异,探讨p53和PCNA与上颌窦恶性肿瘤临床分期、病理分型及淋巴结转移的关系。方法：用免疫组化的方法检测108例上颌窦恶性肿瘤、19例上颌窦良性肿瘤、8例鼻粘膜炎症中p53与PCNA的表达情况。数据统计采用秩和检验,并用平均秩衡量p53和PCNA的阳性表达强度。结果：在上颌窦良性肿瘤和鼻粘膜炎症两组中,p53和PCNA的平均秩分别为42．8、50．3和47．9、46．8;在恶性肿瘤组中,p53和PCNA平均秩分别高达73．0和73．2;在上颌窦恶性肿瘤中,鳞癌p53的平均秩为60．7,比腺癌的平均秩（43．9）高,有显著性差异（P＜0．05）。但临床分期I－Ⅳ期中,p53平均秩分别为46．6、50．1、56．1、55．0,PCNA平均秩分别为60．5、48．8、56．1、53．9;在无淋巴结转移组和有淋巴结转移组中,p53平均秩分别为53．7和57．3,PCNA平均秩分别为53．9和56．4;在生存期＜3年、＜5年和≥5年等3组中,p53平均秩分别为49．9、53．7和48．5,PCNA平均秩分别为45．7、56．9和52．0,均无显著性差异（P＞0．05）。结论：p53和PCNA与上颌窦恶性肿瘤尤其是鳞癌的发生、发展有一定相关性,而与上颌窦恶性肿瘤的临床分型、淋巴结转移和预后无关。     

Immunohistochemical study of oncogene product ras p21, c-myc and growth factor EGF in breast carcinomas.

The expression of the oncogene products ras p21, c-myc and the growth factor EGF (epidermal growth factor) was studied immunohistochemically in the tissue of 119 benign and malignant human breasts. In most cases, histologically normal breast tissues and benign lesions were found to be negative or poorly-expressive for reactivity with each antibody. Similar findings were observed in carcinoma in situ. Invading breast carcinomas demonstrated a significantly higher percentage of stained cells than that observed in benign lesions or carcinoma in situ; forty-two of 66 invasive breast carcinomas (63.6%) were highly-expressive for ras p21, thirty-eight (57.6%) for c-myc and twenty (30.3%) for EGF, but overall correlations between each oncogene expression and the clinical stage, tumor size or degree of differentiation were not found. The overall 5-year survival rate was studied in 58 patients with Stage II and III in association with each oncogene or EGF expression. Their survival rate was significantly effected by the EGF expression (0.05 less than p less than 0.1) but not by ras p21 or c-myc expression. Analysis of 36 specimens available with ER (estrogen-receptor) level revealed a significant correlation between the ER status and c-myc or E2 (estradiol) and a significant inverse correlation between ER status and ras p21 or EGF expression (P less than 0.05). The expression of ras p21, EGF and c-myc was not associated with metastatic tumor progression.     

Overexpression and mutation of p53 in endometrial carcinoma.

Immunohistochemical staining for the p53 protein was performed in 107 snap frozen primary endometrial adenocarcinomas and 15 benign uterine tissues using monoclonal antibody PAb1801. No staining was seen in benign samples, whereas intense nuclear staining of cancer cells consistent with overexpression of the p53 protein was observed in 22 of 107 cancers (21%). p53 overexpression was more frequent in advanced (Stage III/IV) cancers (41%) than in early (Stage I/II) cancers (9%) (P less than 0.001), and also was associated with nonendometrioid histology (P = 0.008), positive peritoneal cytology (P = 0.01), extrauterine metastases (P = 0.003), and negative progesterone receptor status (P = 0.04). To confirm the relationship between p53 overexpression and mutation, p53 mRNA from 8 cancers was reverse transcribed and amplified using the polymerase chain reaction. DNA sequencing revealed point mutations in each of the 5 cancers that overexpressed p53, whereas the wild-type sequence was found in 3 cancers that did not overexpress the protein. Each of the 5 mutations resulted in an amino acid substitution in a highly conserved region of the p53 gene where mutations have been found in other cancers. Further studies are warranted to determine whether the association between p53 overexpression and advanced stage disease is due to accumulation of genetic lesions during tumor progression or whether p53 alterations confer a more virulent phenotype.     

VEGF和p53蛋白在甲状腺肿瘤中的表达及在诊断甲状腺良、恶性肿瘤中的应用价值研究

目的 探讨血管内皮生长因子(VEGF)和p53蛋白在甲状腺肿瘤中的表达以及在良恶性肿瘤诊断中的价值.方法 选取甲状腺肿瘤患者100例,采用免疫组化技术检测组织中VEGF和p53蛋白的表达.结果 甲状腺恶性肿瘤VEGF和p53蛋白阳性表达率分别为62.90%和48.39%,明显高于甲状腺良性肿瘤(P<0.01);VEGF和p53蛋白在不同年龄、性别、TNM分期、病理类型及肿瘤直径的甲状腺恶性肿瘤患者中表达情况差异无统计学意义(P>0.05);甲状腺恶性肿瘤伴淋巴结转移患者VEGF和p53蛋白阳性表达率分别为93.10%和68.97%,明显高于不伴淋巴结转移患者(P<0.01);VEGF判断甲状腺恶性肿瘤灵敏度为62.90%,特异度为89.47%,阳性预测值为90.70%,阴性预测值为59.65%;p53蛋白判断甲状腺恶性肿瘤灵敏度为48.39%,特异度为84.21%,阳性预测值为83.33%,阴性预测值为50.00%;VEGF联合p53蛋白判断甲状腺恶性肿瘤灵敏度为70.97%,特异度为89.47%,阳性预测值为91.67%,阴性预测值为65.63%.结论 VEGF和p53蛋白表达上调可能与甲状腺恶性肿瘤淋巴结转移有关,同时在鉴别良恶性甲状腺肿瘤中有一定的应用价值.     

Genome-wide SNP analysis of Tg.AC transgenic mice reveals an oncogenic collaboration between v-Ha-ras and Ink4a, which is absent in p53 deficiency

Oncogenesis is a progressive process often involving collaboration between various oncogenes and tumor suppressors. To identify those genes that collaborate with oncogenic ras, we took advantage of the Tg.AC transgenic mouse, a line that harbors the v-Ha-ras transgene and spontaneously develops an array of malignant tumors. By crossing Tg.AC mice on an inbred FVB background to other inbred strains, F1 mice were created that could be analysed using genome wide, single nucleotide polymorphism (SNP) screens. Loss of heterozygosity (LOH) in tumors and tumor cell lines marked a somatic event, possibly the inactivation of tumor suppressor gene(s). LOH could also represent DNA damage, a sign of genomic instability in the pretransformed cell. Nonetheless, the screens showed no evidence of such generalized genomic instability. Instead, they revealed a single region of LOH on chromosome 4 that occurred via somatic recombination/gene conversion, generating a region of isoparental disomy. This LOH provided a clue that linked v-Ha-ras to the inactivation of the Ink4a locus in 25 of 32 tumor cell lines. This collaboration is seen regardless of tumor type or genetic background. In contrast, tumors that develop in bitransgenic mice bearing both the v-Ha-ras gene and a heterozygous mutant p53 allele tend to retain the Ink4a locus and instead lose the p53 wild-type allele. This suggests that different strategies can be selected to collaborate with v-Ha-ras in tumorigenesis.     

Diagnostic value of p53 and ki67 immunostaining for distinguishing benign from malignant serous effusions

BackgroundThe differentiation of benign mesothelial cells from malignant tumor cells, primary, or metastatic, in serous effusions based on cytomorphologic features alone can be problematic.PurposeThis study was conducted to evaluate the utility of p53 and ki67 immunocytochemical markers in differentiating benign from malignant tumor cells in serous effusions.Patients and methodsArchival Papanicolaou-stained smears of 91 pleural and peritoneal effusions were retrieved from Cytology Unit, Pathology Department, NCI, Cairo University between 2008 and 2010. Forty-one cases were positive for malignant cells and 50 cases were benign based on cytomorphologic features. Cases having doubt were excluded from the study. The slides were destained and subjected to immunocytochemical staining for p53 and ki67. Histologic sections of colonic carcinoma and tonsillar tissue were used as positive control for p53 and ki67, respectively. Smears having >5% positively stained nuclei for p53 were taken as positive and labeling index ?10% of ki67 was considered positive. Frequencies of the individual immunocytochemical stains; p53 and ki67, in benign and malignant effusion as well as the combination of both stains were calculated.Resultsp53 immunostaining showed nuclear positivity in 31 out of 41 malignant effusions (75.6%) and in 3 out of 50 benign effusions (6%), p < 0.005. p53 had 75.6% sensitivity, 94% specificity, 91.2% PPV, and 82.5% NPV. ki67 immunostaining was positive in 30 out of 41 malignant effusions (73.2%) and in 17 out of 50 benign effusions (34%), p < 0.05. ki67 had 73.2% sensitivity, 66% specificity, 63.8% PPV, and 75% NPV. Cases were then analyzed for combined immunoprofile of p53 and ki67. Among the 24 cases that coexpressed both antigens, 22 cases (91.7%) were malignant. Thirty two out of 34 cases (94.1%) that showed negative results for both antigens were benign. For the cases that showed p53 immunostaining only, 9 out of 10 cases (90%) were malignant. Fifteen out of 23 cases (65.2%) that showed ki67 immunostaining were benign.ConclusionBenign and malignant effusions showed significantly different staining pattern for p53 and ki67. When used individually, p53 immunostaining can truly diagnose 75.6% and 94% of the malignant and benign cases, respectively. ki67 immunostaining can correctly identify 73.2% and 66% of the malignant and benign cases, respectively. When used in combination, 91.7% of p53 and ki67 positive cases were malignant while 94% of p53 and ki67 negative cases were benign. Hence they could be used when the cytomorphology fails to provide a definitive diagnosis.     

Ki-67抗原在原发性胆囊癌中的表达及其意义

目的探讨Ki-67抗原表达与原发性胆囊癌病理生物学行为的关系.方法采用免疫组化S-P法,检测胆囊良、恶性病变中Ki-67抗原的表达情况,以其表达阳性率评估胆囊癌组织的增生活性.结果Ki-67抗原在胆囊癌组织中的表达量显著高于胆囊良性病变(P＜0.01).但Ki-67抗原的表达强度与胆囊癌组织学类型、Nevin分期及病理分级无明显相关性(P＞0.05),与胆囊癌的突变型p53基因产物表达量呈明显正相关(P＜0.05).结论Ki-67抗原作为1个代表增殖活性的肿瘤标志,其过量表达是胆囊癌高度恶性的生物学行为的客观指标之一,对胆囊恶性肿瘤的病理诊断有较高的实用价值.p53基因可能通过基因突变增强胆囊癌细胞的增殖活性,从而使Ki-67抗原表达量明显增加.     

突变型p53蛋白在胃癌和癌旁组织中的表达及形态定量分析

目的　应用图像分析对胃癌、癌旁组织中p5 3蛋白阳性细胞核进行形态测量 ,根据核间差异 ,为胃部良恶性病变的鉴别提供依据。方法　采用SP免疫组化法和图像分析技术分别对 3 3例胃癌和 17例癌旁组织中p5 3阳性细胞核进行检测。结果　免疫组化结果显示 :胃癌中p5 3蛋白阳性表达率和阳性细胞密度均高于癌旁组织 (P <0 .0 5 )。图像分析结果显示 :胃癌和癌旁组织中p5 3阳性细胞核在等效直径、形状因子和异形指数各参数上差异具有显著性 (P <0 .0 1)。结论　以上结果表明 :图像分析能客观对肿瘤标记物进行参数识别 ,可以作为鉴别胃良恶性病变的一个参考指标 ,并有助于胃癌的早期预防。     

Immunohistochemical profile of phyllodes tumors of the breast

The immunohistochemical profiles of 16 cases of phyllodes tumor of the breast (9 benign and 7 malignant) from 15 patients were examined by the labeled streptavidin biotin method. The expression of Ki-67, p53, bcl-2, alpha-smooth muscle actin (alpha-SMA), desmin, S-100 protein, estrogen receptor (ER), and progesterone receptor (PgR) was analyzed. The number of Ki-67-positive stromal cell nuclei of malignant phyllodes tumor were significantly more prominent than the benign tumors. The p53 expression on the stromal cell nuclei showed a significant difference between malignant and benign cases (86% vs 22%; p<0.05). bcl-2 was regularly seen on the luminal cell cytoplasm and stromal cell labeling showed no significant difference between malignant and benign cases (29% vs 33%). Stromal cells were alpha-SMA positive but refractory among cases, and desmin and S-100 protein were negative. PgR was expressed in all 16 cases and ER in most cases (12/16) the expression of which was restricted to luminal epithelial cell nuclei. These findings indicate that the Ki-67 labeling index and p53 expression in the stroma would be a good diagnostic parameter distinguishing benign tumors from malignant tumors. However, the absence of steroid receptor expression in stromal cells suggests the ineffectiveness of hormonal therapy for phyllodes tumor of the breast.     

Detection of p53 Gene Mutations in Aspiration Biopsy Specimens from Suspected Breast Cancers by Polymerase Chain Reaction-Single Strand Conformation Polymorphism Analysis

Genomic DNA was extracted from aspiration biopsy specimens taken from 15 suspected cases of breast cancer, including 7 known cases of breast cancer, and the p53 gene was studied for evidence of mutation by using a polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. In 5 of the 15'cases (33%), p53 gene mutation was identified and these tumors were subsequently histologically diagnosed as malignant. Further, DNA flow cytometry of the 15 tumors demonstrated that 6 (40%) were aneuploid and malignant, whereas 9 (60%) were diploid and benign. It was also found that the tumor cells in 5 aspirated cases that showed p53 gene mutations were all aneuploid, the p53 protein expression was positive, and the tumors were proved to be histologically malignant. It was thus concluded that the detection of p53 gene mutation by PCR-SSCP analysis of aspirated biopsy specimens from suspected breast cancers is a helpful method for achieving a more accurate diagnosis.     

Correlations of bcl-2 and p53 expression with the clinicopathological features in tongue squamous cell carcinomas

bcl-2 oncogene prolongs cell survival by inhibition of apoptosis. p53 tumor suppressor gene participates not only in cell proliferation control but also in induction of apoptosis. The expression of both bcl-2 and p53 proteins in 52 primary tongue squamous cell carcinomas (SCCs) was immunohistochemically explored in correlations with clinico-pathological features, patient's prognosis and apoptosis index (AI) of this tumor type. bcl-2 and p53 expression were identified in 26/52 (50%) cases and 31/52 (60%) cases, respectively. The frequency of bcl-2 expression was associated with tumor histologic grade (P = 0.0128) and marginally with mode of tumor invasion (P = 0.0671) but not with lymph nodal involvement. The frequency of p53 expression was associated with mode of tumor invasion (P = 0.0458) and pN status (P = 0.0224) but not with tumor histologic grade. Moreover, the three combined bcl-2/p53 staining patterns of bcl-2-/p53-, bcl-2+/p53- and bcl-2-/p53+, and bcl-2+/p53+ were significantly correlated with tumor histologic grade (P = 0.0299), mode of tumor invasion (P = 0.0022) and pN status (P = 0.0024). In addition, the frequent appearance of bcl-2 protein expression was associated with a decrease in AI (P = 0.0290). Our results suggest that the combined investigation on the two biological markers may have value in assessment of tumor aggressiveness, and that the suppressing mechanism of bcl-2 oncogene in regulation of apoptosis preserves in tongue SCC.     

p16、p53、BRAF、Bcl-2在卵巢浆液性肿瘤组织中的表达及临床意义

目的:探讨卵巢浆液性肿瘤组织中p16、p53、BRAF、Bcl-2的表达及临床意义。方法:收集宁夏医科大学总医院病理科2017年至2018年确诊的卵巢浆液性肿瘤136例,其中浆液性囊腺瘤52例,交界性囊腺瘤22例,低级别浆液性癌18例,高级别浆液性癌44例;另收集卵巢良性肿瘤和卵巢癌手术切除标本各30例。分别采用免疫组织化学SP法检测p16、p53、BRAF、Bcl-2的表达,实时定量PCR法检测p16、p53在卵巢良恶性肿瘤组织中的表达。结果:卵巢浆液性囊腺瘤、交界性囊腺瘤、低/高级别浆液性癌组织中p16的阳性率分别为3.8%、45.5%、88.9%、81.8%,p53为0、9.1%、55.6%、45.5%,BRAF为46.2%、45.5%、22.2%、31.8%,Bcl-2为46.2%、45.5%、38.9%、47.7%。不同类型浆液性肿瘤组织中p16、p53表达均有显著性差异（P＜0.001）,但BRAF、Bcl-2表达未见明显差异。与卵巢良性肿瘤相比,p16在交界性肿瘤、卵巢癌中的阳性表达明显升高,差异有显著统计学意义（P＜0.012 5）;p53在卵巢癌中的阳性表达明显高于良性肿瘤（P＜0.001）;p16和p53的表达呈正相关（P＜0.05）。p53、Bcl-2与卵巢癌淋巴结转移有相关性（P＜0.001）,p16、p53、Bcl-2与盆腔侵犯有关（P＜0.05）,p53、BRAF、Bcl-2与CA125表达有不同程度相关性（P＜0.05）。p16、p53联合检测对卵巢癌诊断的敏感性和特异性为90.0%、76.7%。结论:p16、p53、BRAF、Bcl-2参与卵巢癌的发生发展,p16和p53基因突变可能在卵巢浆液性肿瘤的恶性进展中发挥作用,联合检测p16、p53对卵巢癌诊断有指示意义。