Expression of vascular endothelial growth factor in renal cell carcinoma and the relation to angiogenesis and p53 protein expression

BACKGROUND AND OBJECTIVES: Vascular endothelial growth factor (VEGF) seems to play an important role in tumor angiogenesis. The tumor-suppressor gene p53 has been thought to regulate VEGF expression. We investigated the effect of VEGF expression on renal cell carcinoma (RCC) and the correlation between the expression of VEGF and tumor angiogenesis and p53 protein expression. METHODS: Sixty-two RCCs were examined by immunohistochemical studies with anti-VEGF, anti-p53, and anti-CD34 antibodies. RESULTS: Forty tumors (80.6%) were classified as VEGF positive, and 28 tumors (45.2%) were positive for p53 protein. The microvessel density was 75.3 +/- 33.5. A significant correlation was found between VEGF expression and both the nuclear grade (P < 0.05) and the TNM stage (P < 0.05). The tumors with VEGF expression had a significantly higher microvessel density than those without VEGF expression (P < 0.01). There was no statistically significant correlation between p53 protein and VEGF expression. No statistically significant differences in survival were found to be associated with microvessel density, VEGF expression or p53 protein expression. By using multivariate survival analyses, nuclear grade (P < 0.05) and TNM stage (P < 0.05) were the only independent prognostic factors. CONCLUSIONS: Our data do not show a direct regulation of VEGF expression by p53. We suggest that VEGF expression plays a role in the promotion of angiogenesis in RCC.     

Nuclear DNA content-derived parameters correlated with heterogeneous expression of p53 and bcl-2 proteins in clear cell renal carcinomas

BACKGROUND: p53 and bcl-2 are two key genes involved in cell cycle and cell death regulation. Altered expression or mutation of these genes has been found in human cancers and also has been identified in clear cell renal carcinoma (RCC). Their role in RCC progression, however, is still unclear. By contrast, the prognostic significance of ploidy and S-phase fraction (SPF) have been studied extensively in RCC. To better characterize the biologic role of p53 and bcl-2 oncoproteins in RCC, we offer a multisample correlative analysis of the expression of these two proteins with ploidy and SPF. METHODS: Ploidy and SPF along with p53 and bcl-2 expression were analyzed in 296 specimens, selected by multiple sampling of 33 consecutive operable RCCs. The expression of p53 and bcl-2 proteins was studied by immunohistochemistry, and SPF and tumor ploidy were studied by flow cytometry. RESULTS: In our study, 4 of 32 (12.5%) were found to be diploid, and 28 of 32 (87.5%) cases showed an abnormal DNA content. Among the aneuploid tumors, 14 of 28 (50%) were multiploid. Heterogeneous DNA content was detected in 21 of 32 (65.6%) tumors and was correlated with the more advanced Robson stage tumor (P = 0. 03). Intratumor heterogeneity also was detected for p53 and bcl-2 protein expression. Expression of p53 protein correlated with the lack of bcl-2 protein expression (P = 0.0032), aneuploidy (P < 0. 0001), and high SPF (P = 0.0006), whereas bcl-2 expression was associated with a normal DNA content (P < 0.0001) and low SPF (P = 0. 035). CONCLUSIONS: Within each RCC, p53 and bcl-2 expression is markedly heterogeneous. Our results depicted a scenario in which bcl-2 protein, expressed by normal renal parenchyma, is still present in euploid cell clones of RCC but disappears during the progression of renal neoplasm toward a more aggressive phenotype characterized by overexpression of p53 protein, aneuploidy, and high SPF.     

大肠癌组织p53、PCNA表达与临床病理及预后的关系

目的：探讨突变型ｐ５３ 蛋白、增殖细胞核抗原（ＰＣＮＡ） 在结直肠癌细胞中的表达情况与临床病理及预后的关系。方法：用ＬＳＡＢ 免疫组化方法检测１７２ 例癌组织中的ｐ５３ 蛋白、ＰＣＮＡ 的表达情况,用Ｌｏｇｉｓｔｉｃ 回归分析ｐ５３ 表达的相关因素,Ｃｏｘ 模型分析ｐ５３ 、ＰＣＮＡ 表达对预后的的影响。结果：ｐ５３ 、ＰＣＮＡ 阳性率分别为４３－６ ％ （７５／１７２） 、９１－３ ％ （１５７／１７２） 。ｐ５３ 表达与临床病理因素无关,ｐ５３ 阳性预后比阴性差,ｐ５３ 阳性常伴有ＰＣＮＡ 过度表达,但ＰＣＮＡ 高表达,预后有好的趋势。结论：结直肠癌ｐ５３ 突变的癌细胞多呈高增殖状态,ｐ５３ 阳性、ＰＣＮＡ 中、低强度表达是预后差的生物学指标。ＰＣＮＡ 高表达,是癌细胞处于高增殖状态、对化疗敏感的标志,对该类病人给予辅助化疗可望提高根治术疗效。     

mdm2 expression as a prognostic indicator in clear cell renal cell carcinoma: comparison with p53 overexpression and clinicopathological parameters.

The present study was designed to analyze the expression of p53 and mdm2 in clear cell renal cell carcinoma with special emphasis on their association with tumor grade and clinical outcome. In particular, the value of individual protein overexpression as well as combined p53/mdm2 positivity was evaluated because both proteins are functionally connected, and their expression is controlled by an autoregulatory feedback loop. A cohort of 97 clear cell renal cell carcinomas was analyzed. The overexpression of mdm2 and p53 proteins was investigated on paraffin-embedded material by using monoclonal antibodies. Eighteen tumors showed mdm2 positivity, whereas 35 of the tumors overexpressed p53. Whereas p53 and mdm2 positivity correlated significantly (P = 0.00004), no correlation could be found between mdm2 protein overexpression and tumor stage, lymph node involvement, and presence of distant metastases. mdm2 positivity was found significantly more frequently in tumors of higher grade. In univariate analysis, there was a statistically significant correlation between p53 and mdm2 overexpression in the same tumor and poor survival (P = 0.00179). Multivariate analysis revealed that coincident mdm2/p53 overexpression, the presence of distant metastases, and tumor grade were independent predictors for tumor progression. Our results indicate that mdm2/p53 co-overexpression, nuclear grade, and preoperative presence of distant metastasis are independent predictors for poor survival.     

Overexpression of p53 associated with tumor angiogenesis, tumor cell proliferation, and prognosis in gastric carcinoma

Mutations in the p53 gene seem to be the most common genetic change in human malignancies. Recently, it was reported that p53 mutation was significantly associated with prognosis in various cancers. In this study, we investigated the correlation between p53 overexpression and prognosis of gastric carcinoma using immunohistochemical staining with an anti-p53 antibody. Although there was no significant association between p53 status and various clinicopathologic factors, prognosis of patients with p53-positive tumors was significantly worse than of those with p53-negative: tumors. Both microvessel count (MVC; the mean number of microvessels in the five areas of highest vascular density at 200x magnification) and PCNA labeling index (PCNA LI; percentage of positive cells per more than 500 tumor cells) were significantly higher in p53-positive tumors than in p53-negative tumors. In summary, it is suggested that p53 overexpression is closely associated with tumor angiogenesis, tumor cell proliferation and prognosis of gastric carcinoma.     

大肠腺瘤癌变过程中β-catenin、p53和增殖细胞核抗原表达的研究

目的 探讨β－catenin、p53和增朱（PCNA）在大肠腺瘤癌变中的可能作用。方法 以免疫组织化学方法检测77例大肠腺瘤（CRA）及癌变组织中β－catenin、p53蛋白及PCNA的表达情况。结果 CRA随上皮不典型增生程度的提高以及癌变的出现,β－catenin异常表达率逐渐增高（P＜0.05）。伴中、重度上皮不典型增生的CRA和CRA癌变的出现,β－catenin核表达阳性率均明显高于上皮轻度不典型增生的CRA（P＜0.01）。CRA伴轻度不典型增生和CRA伴中、重度不典型一及CAR癌变3组的p53蛋白和PCNA表达依次增高,其阳性率分别为10.3%、43.8%、75.0%和17.2%、62.5%、87.5%。在β－catenin核表达阳性者中,其PCNA的强阳性表达率明显高于β－catenin核表达阴性者（69.7%和36.4%,P＜0.05）;在p53蛋白表达阳性者中,其PCNA的强阳性表达率明显高于p53表达阳性者（72.4%和37.5%,P＜0.05）。在CRA癌变组中,有50.0%可见β－catenin和p53同时表达。结论 β－catenin、p53和PCNA在CRA癌变过程中可能发挥了重要作用。     

Clinical significance of MUC1 and MUC2 mucin and p53 protein expression in colorectal carcinoma

BACKGROUND: Up-regulation of MUC1, down-regulation of MUC2 and p53 overexpression are seen in colorectal carcinomas. However, there have been few reports about the associations between MUC1, MUC2 and p53 expression and metastatic potential. The aim of this study was to investigate MUC1, MUC2 and p53 expression in colorectal carcinoma with special reference to regional and distant metastasis. METHODS: Eighty-six colorectal carcinomas were collected from patients undergoing tumor resection. Sections were used for MUC1, MUC2 and p53 immunostaining. Cancers were regarded as MUC1 or MUC2 positive when the positive cells were beyond 30% of cancer cells. Cancers with diffuse or nested patterns were regarded as having p53 overexpression. RESULTS: Of 86 cancers, 37 (43%) were MUC1 positive, 28 (33%) were MUC2 positive and 59 (69%) showed p53 overexpression. A difference was observed only in the frequency of MUC1 positivity with respect to depth of tumor invasion. Neither depth of tumor invasion nor histological differentiation had a positive correlation with MUC1, MUC2 and p53 overexpression. The frequency of MUC1 positive cells in Dukes' C and D tumors was significantly higher than that in Dukes' A and B tumors. The frequency of MUC1 positivity in tumors with hepatic involvement was significantly higher than that in tumors without hepatic involvement (100 vs 39%; p < 0.01). There was no difference in the frequency of MUC2 or p53 positivity in Dukes' stage or hepatic metastasis. MUC1 immunoreactivity of the surface was identical with that of the whole tumor in 81% (70/86) of carcinomas, MUC 2 in 87% and p53 in 100%. CONCLUSIONS: The results suggest that up-regulation of MUC1 is involved in the progression from the non-metastatic to the metastatic stage and that p53 abnormality is not directly involved in it. The data also imply that immunostaining of preoperative biopsy samples is useful for evaluating the immunoreactivity of the whole tumor.     

DNA ploidy analysis and cell proliferation in congenital sacrococcygeal teratomas

BACKGROUND: Congenital sacrococcygeal teratoma is the most common germ cell tumor in infants and children. It usually is diagnosed at birth, is benign, and consists of fully differentiated mature tissues. Congenital sacrococcygeal teratomas (SCTs) also may contain immature tissues, most commonly of neural origin. The proportion of malignant teratomas increases with advancing age, but the relation between mature and immature SCTs is not well understood. Thus, it is very important to determine proliferative activity, DNA ploidy, and DNA index to predict biologic behavior of these tumors. METHODS: DNA ploidy and cell proliferation were analyzed by flow cytometry, and the expression of proliferating cell nuclear antigen (PCNA) and Ki-67 were analyzed immunohistochemically on paraffin embedded tissue. RESULTS: All the tumors that were surgically treated within 3 months after birth, including immature teratoma, were diploid. Strongly positive PCNA immunostaining was found in both immature teratomas, and weakly positive PCNA was found in nine cases. Weak positivity for Ki-67 was observed in 2 cases, and moderate positivity was observed in 6 cases including immature teratomas. CONCLUSION: The value of flow cytometry in the prediction of biologic behavior of congenital SCT should be analyzed further. Our results suggest that Ki-67 and especially PCNA may reflect the proliferative activity of these tumors.     

pT1 clear cell renal cell carcinoma: a study of the association between MIB-1 proliferative activity and pathologic features and cancer specific survival

BACKGROUND: The majority of patients with pT1 clear cell renal cell carcinoma (RCC) are cured with nephrectomy. However, a few patients will die of RCC. In several studies, MIB-1 proliferative activity was identified as an independent predictor of survival in patients with RCC. The objective of the current study was to examine MIB-1 proliferative activity in a large series of patients with pT1 clear cell RCC who were treated uniformly with radical nephrectomy, and to examine the association between proliferative activity and cancer specific survival in a multivariate model incorporating tumor size, nuclear grade, and tumor necrosis. METHODS: Patients with solitary pT1 clear cell RCC who underwent radical nephrectomy between 1970-1997 were eligible for the current study. For each of the 40 patients who died of RCC, a stratified random sample of at least 3 year-matched patients who still were alive or had died of other causes at the time of last follow-up was selected. Patient age at nephrectomy, patient gender, tumor size, nuclear grade, and tumor necrosis were evaluated, and the MIB-1 proliferative activity was assessed using digital image analysis. Univariate and multivariate Cox proportional hazards models were fit to assess the features associated with cancer specific survival. The associations between MIB-1 proliferative activity and pathologic features were assessed using the Wilcoxon rank sum test. RESULTS: The mean MIB-1 value for those patients who died of clear cell RCC was 6.5% compared with 3.6% for those patients who died of other causes or were still alive at the time of last follow-up. Patients whose tumor had an MIB-1 proliferative activity > o r = 5.0% were more than twice as likely to die of RCC than patients whose tumors had a MIB-1 activity < 5% (P = 0.02). However, after adjusting for tumor size, nuclear grade, and necrosis, MIB-1 proliferative activity was not found to be associated significantly with cancer specific survival. There was a significant association between MIB-1 proliferative activity and tumor size, nuclear grade, and necrosis. CONCLUSIONS: After adjusting for tumor size, nuclear grade, and necrosis, MIB-1 proliferative activity was not found to be an independent predictor of outcome in patients with pT1 clear cell RCC who were treated with radical nephrectomy. There was a significant association between MIB-1 and other well established pathologic prognostic features of pT1 clear cell RCC.     

Proliferation- and Apoptosis-related Proteins in Intracranial Ependymomas: An Immunohistochemical Analysis

As the value of grading of ependymomas is currently debated we studied the expression of proliferation- and apoptosis-related proteins in these tumors as these mechanisms both are suggested to be important in tumor growth. We characterized the immunohistochemical expression of p53, Mdm2, Bcl-2, and Bax in 51 intracranial ependymomas. We also assessed the apoptosis- and proliferation-index, measured by MIB-1, PCNA-immunohistochemistry, and analyzed the clinical parameters. Of all used antibodies, the correlation with survival and the correlation among ordered categories was assessed. None of the analyzed immunohistochemical variables were significantly correlated with tumor grade. On the other hand, PCNA, MIB-1, and p53 were significantly related to the survival of the patient. In multivariate analysis, p53 was the only independent predictive variable (p = 0.0132). Conclusion: The strongest predictors of survival in univariate analysis were the expression of PCNA, MIB-1 and p53. In multivariate analysis a p53 expression >1% showed to be significantly related with a worse survival. The predicting value of p53 expression has to be confirmed by others before solid conclusions can be made. Apoptosis seems not to be an important mechanism in tumor growth in ependymomas. The expression of Mdm2, Bcl-2, and Bax were not related to survival.     

Expression of KIT (CD117) in renal cell carcinoma and renal oncocytoma

OBJECTIVE: Overexpression of KIT (CD117), a tyrosine kinase receptor, has been reported in a variety of tumors, some of which are susceptible to therapy with imatinib mesylate. Our aim was to analyze KIT expression immunohistochemically in renal cell carcinomas (RCCs) and in oncocytomas. METHODS: Routinely processed, paraffin-embedded specimens from 61 RCCs and 13 renal oncocytomas were investigated immunohistochemically. Cytoplasmic and membrane-bound KIT staining of tumor cells was determined semiquantitatively. A subset of cases was additionally analyzed for point mutations of c-kit exon 17 by peptide nucleic acid-mediated nested polymerase chain reaction-clamping. RESULTS: All cases of oncocytomas and chromophobe RCCs showed membrane-bound KIT positivity, while about three-quarters of cases showed cytoplasmic reactivity. All other types of RCC were found KIT negative. Within the group of chromophobe RCCs, negative cytoplasmatic KIT reactivity was significantly correlated with advanced tumor stage (pT > or = 2; p = 0.036). Analysis of c-kit exon 17 revealed no 'gain-of-function' mutation like the codon 816 Asp-->Val mutation (D816V). Conclusions: KIT expression is a hallmark of oncocytoma and chromophobe RCC. Since all other types of RCC were found to be KIT negative, immunohistochemical KIT reactivity may be used as an additional diagnostic criterion to distinguish chromophobe RCC from other RCC types. KIT reactivity and the absence of c-kit mutation D816V in chromophobe RCC justify speculations that imatinib mesylate therapy could be effective in patients with advanced disease.     

Alterations of G1-S checkpoint in chordoma: the prognostic impact of p53 overexpression

BACKGROUND: To the authors' knowledge, little is known regarding the alterations of G(1)-S checkpoint and their significance in chordoma, a rare bone tumor. The authors investigated the clinicopathologic relevance of cell cycle abnormalities in chordoma. METHODS: The expression levels of p53, murine double minute 2 (MDM2), retinoblastoma protein (pRb), cyclin D1, p16(INK4a), and p27(Kip1) were investigated using immunohistochemical techniques; p53 mutations were studied by polymerase chain reaction (PCR)-single-strand conformation polymorphism, and mdm2 amplification was analyzed using real-time quantitative PCR. The results were compared with clinicopathologic parameters in 101 lesions. RESULTS: Approximately 10-45% of primary tumors presented alterations of p53, MDM2, cyclin D1, and pRb proteins; most tumors lacked expression of p16(INK4a) and p27(Kip1). Alterations of p53, MDM2, cyclin D1, and pRb proteins were found to have cooperative effects on both higher proliferative ability (MIB-1 labeling index [LI]) and increased nuclear pleomorphism, a previously described prognostic indicator for patients with chordoma. Multivariate analyses revealed that, among these alterations, p53 overexpression was the only independent factor for higher MIB-1 LI. At the genetic level, mdm2 gene amplification was detected in 15.4% of the lesions but did not correlate with MDM2 overexpression or other clinicopathologic parameters. No p53 mutations were detected in the current series. Survival analysis revealed that p53 overexpression, but no other cell cycle alterations, was associated with a reduced overall survival. CONCLUSIONS: Accumulation of cell cycle alterations led to an increased MIB-1 LI and nuclear pleomorphism, a previously described prognostic indicator in chordoma. The authors believe that p53 overexpression in particular is associated with an unfavorable prognosis in patients with chordoma.     

Frequent expression of Bcl-2 in renal-cell carcinomas carrying wild-type p53

The p53 tumor-suppressor gene is the most commonly mutated gene in cancer. However, p53 gene alterations are infrequent in renal-cell cancer (RCC). Bcl-2 has been shown to inhibit apoptosis triggered by wild-type p53 and an inverse correlation between Bcl-2 expression and p53 mutation has been observed in breast cancer and glioma. To characterize the expression of bcl-2 in RCC and its relationship to the p53 status, we analyzed 25 RCCs by immunohistochemistry for Bcl-2 and p53, Southern hybridization for bcl-2, and PCR-SSCP and sequencing for p53. Positive Bcl-2 staining was detected in 17 of 25 RCCs, whereas positive p53 staining was seen in only 1. Amplification of bcl-2 or p53 mutation was not detected in any of the tumors. Bcl-2 protein was expressed in all 7 RCC cell lines examined. Only one of the 7 lines had p53 mutation. These results suggest that overexpression of bcl-2, rather than p53 mutation, may prevent apoptosis during RCC development. © 1996 Wiley-Liss, Inc.     

Expression of vascular endothelial growth factor and p53 protein in association with neovascularization in human malignant gliomas

We examined the expression of vascular endothelial growth factor (VEGF) protein, p53 protein, and the MIB-1 index in 43 patients with malignant gliomas in relation to tumor vascularization by an immunohistochemical method. Factor VIII-related antibody was employed for the evaluation of the vascularity and endothelial proliferation. Of the 42 cases of malignant gliomas, 36 (86%) demonstrated immunoreactivity for VEGF in their tumor cells, whereas 22 (52%) had VEGF in their endothelial cells. There was a tendency for the vascularity to be correlated with the immunoreactivity for VEGF (coefficient, 0.340). In addition, a marked increase in endothelial proliferation was evident in cases showing moderate to strong positivity for VEGF as compared with the others. Immunoreactivity for VEGF was found mostly in the malignant gliomas without p53 overexpression and/or with p53 overexpression. However, statistical analysis revealed a correlation between the grade of p53 overexpression and the grade of VEGF expression (coefficient, 0.507), but not between the VEGF and MIB-1 index in our series. There was a tendency for the MIB-1 indices to increase in correlation with increasing vascularity.     

p53、c-erbB2基因、增殖细胞核抗原表达与卵巢上皮性癌预后的关系

背景与目的：p53、c-erbB2基因和增殖细胞核抗原（proliferating cell nuclear antigen,PCNA)的表达与卵巢癌预后关系问题已有报道,由于研究方法、样本大小等方面的不同,结果存在差异。为进一步探讨p53、c-erbB2基因和PCNA表达与卵巢上皮性癌预后的关系,我们进行了本研究。材料与方法：1990年3月1日至1994年3月31日间确诊的卵巢上皮性癌共84例,采用标记的链白素－生物素辣根过氧化酶复合物（LSAB）免疫组化方法检测癌组织中p53、c-erbB2基因和PCNA的表达,使用SPSS8．0版分析它们的表达与卵巢癌患者平均生存期、5年生存率之间的关系。结果：本组84例癌组织中,p53、c-erbB2和PCNA表达的阳性率分别为58．3％（49／84）、77．5％（65／84）和100％（84／84）。单因素分析显示,c-erbB2过度表达和PCNA表达强度与患者的平均生存期、5年生存率均呈负相关（P值分别为0．05和小于0．01）,未发现p53蛋白表达与患者的平均生存期、5年生存率之间存在相关性（P＞0．05）。多因素分析发现卵巢上皮性癌的预后与临床分期、组织分化程度有关,而与p53、c-erbB2和PCNA的表达均无相关性。结论：p53的表达与卵巢上皮性癌的预后无关,而c-erbB2、PCNA表达对卵巢上皮性癌预后的影响是间接的。临床分期、组织分化程度仍是卵巢上皮性癌独立的预后因素。     

Tracking sub-clonal TP53 mutated tumor cells in human metastatic renal cell carcinoma

Renal Cell Carcinomas (RCCs) are heterogeneous tumors with late acquisition of TP53 abnormalities during their evolution. They harbor TP53 abnormalities in their metastases. We aimed to study TP53 gene alterations in tissue samples from primary and metastatic RCCs in 36 patients followed up over a median of 4.2 years, and in xenografted issued from primary RCCs.In 36 primary RCCs systematically xenografted in mice, and in biopsies of metastases performed whenever possible during patient follow-up, we studied p53-expressing tumor cells and TP53 gene abnormalities.We identified TP53 gene alterations in primary tumors, metastases and xenografts.Quantification of tumors cells with TP53 gene alterations showed a significant increase in the metastases compared to the primary RCCs, and, strikingly, the xenografts were similar to the metastases and not to the primary RCCs from which they were derived.Using laser-microdissection of p53-expressing tumor cells, we identified TP53-mutated tumor cells in the xenografts derived from the primary RCC, and in a lung metastasis later developed in one patient. The mutation enabled us to track back their origin to a minority sub-clone in the primary heterogeneous RCC.Combining in situ and molecular analyses, we demonstrated a clonal expansion in a living patient with metastatic RCC.     

Cytogenetic and molecular findings in 75 clear cell renal cell carcinomas

Cytogenetic analysis of 75 clear cell renal cell carcinomas (RCC) from adult patients revealed abnormal karyotypes in 59 (79%) tumors. Among structural abnormalities, the most frequent were deletions and unbalanced translocations leading to loss of 3p (found in 68% of karyotypically abnormal tumors), followed by rearrangements of chromosomes 5 (in 37%) and 1 (in 20%). Fifteen unbalanced interchromosomal rearrangements and one reciprocal translocation have not been hitherto reported in clear cell RCC. The most common numerical aberrations were trisomy 7, seen in 44% of tumors, and loss of chromosome Y, detected in 48% of RCCs diagnosed in male patients. In 25 tumors, loss of heterozygosity (LOH) analysis was performed using five polymorphic markers spanning region 3p13-p25. LOH was identified in 10 RCCs with 3p loss detected cytogenetically and 4 karyotypically aberrant tumors without cytogenetic rearrangements of 3p; no LOH was found in 3 tumors with 3p loss seen at the cytogenetic level. Overall, 3p loss was detected by cytogenetic and/or LOH analyses in 75% of RCCs with abnormal karyotype studied. The presence or absence of 3p loss did not correlate with tumor size, nodal involvement, tumor grade or its ability to metastasize. However, karyotypes of metastasizing tumors contained more aberrations than those of non-metastasizing RCCs (5.5 versus 2.9 aberrations per tumor, respectively), and -14/14q-, -17 and -10 were significantly more frequent in metastasizing tumors, suggesting that these aberrations might contribute to the progression of RCC. One patient had t(X;1)(p11.2;p34) as a sole abnormality in the stemline. This is the sixth case with this translocation reported to date. Together with our case, all but 1 RCC with t(X;1)(p11.2;p34) had morphology with a clear cell component, which contrasts these RCCs from tumors harboring t(X;1)(p11.2;q21) that largely had papillary morphology.     

膀胱移行细胞癌中p53突变、bcl-2和PCNA表达的临床意义(英文)

目的探讨膀胱癌中 bcl-2、p53、PCNA 表达与细胞增殖、凋亡和临床病理学参数之间的关系。方法 SABC 免疫组化分折62例(T1G1-G339例,T2-T4aG3 NOM023例)甲醛固定和石蜡包埋的膀胱癌标本 bcl-2、p53和 PCNA 蛋白的免疫反应性。平均随访37个月,24例复发。增殖指数(PI)表示肿瘤细胞中 PCNA 阳性细胞百分比。TUNEL 法检测细胞凋亡,凋亡指数(AI)表示肿瘤细胞中凋亡细胞的百分比。结果 62例膀胱癌中,50例(80.0%)发生 p53突变,与 G1(72.7%)和 G2(78.5%)相比较 G3(91.3%)更多见(P<0.05);pT2期(95.7%)p53突变率较 pTa-1期(74.3%)高(P<0.01)。14例(22.5%)发现有 bcl-2表达,bcl-2表达阳性率 G3明显高于 G1和 G2(P<0.05),与分期无关(P>0.05)。Bcl-2表达与 p53突变无关。在膀胱癌中,PI 为17.2%～41.8%(平均为22.4%),AI 为1.9%～3.5%(平均为2.9%)。统计分析显示 PI 与肿瘤分级、分期关系密切,AI 与肿瘤的分级有明显关系。结论结果表明,p53突变与浸润性行为呈正相关。在膀胱癌中 p53和 PCNA 过表达可能能提供有价值的预后信息。随着肿瘤的进展,肿瘤细胞过度增殖可能伴有频繁的凋亡,但增殖指数的增加明显强于凋亡指数的增加。     

Preoperatively irradiated rectal carcinoma: analysis of the histopathologic response and predictive value of proliferating cell nuclear antigen immunostaining

OBJECTIVES: To investigate the relationship between the histopathologic effects of preoperative chemoradiotherapy in rectal cancer and the proteins, proliferating cell nuclear antigen (PCNA) and p53. METHODS: Samples from 73 tumors were examined. The histopathologic effects observed in the resected specimens induced by preoperative chemoradiotherapy were correlated with the inmunohistochemical expression of PCNA and p53 in biopsies obtained by rectoscopy before chemoradiotherapy. RESULTS: Thirty-five tumors showed a high PCNA index (48%). Nuclear accumulation of p53 protein was detected in 53 tumors (72%). Specimens were assigned one of four grades based on the amount of residual viable tumor. Three neoplasms (4%) showed complete regression; 8 other carcinomas (11%) showed only small numbers of tumor cells scattered within the field of stromal reaction. In these cases, it was considered that the tumor had responded significantly to radiotherapy. Tumors with a high PCNA index responded to chemoradiotherapy more frequently (8/35; 72%) than tumors with a low index (3/38; 43%) (p = 0.07). p53-negative tumors responded more frequently (4/20; 20%) than positive tumors (7/53; 13.2%) (p = 0.50). When pathologic and immunohistochemical characteristics of the tumors were included in a logistic regression model, only high PCNA index (odds ratio 5.35, 95% confidence interval 1.07-26.7) (p = 0.04) was significantly associated with the histologic response to preoperative chemoradiotherapy. CONCLUSION: High proliferative activity of rectal cancer, as determined by PCNA immunostaining, is predictive of the response to preoperative chemoradiotherapy.