Prognostic significance of p53 overexpression in gastric and colorectal carcinoma.

p53 expression was examined in 55 gastric and 107 colorectal carcinomas with an immunoperoxidase technique, using the polyclonal antibody CM1 on routinely fixed, paraffin embedded tissue. p53 protein was detected in 47% gastric and in 46% colorectal carcinomas and found to correlate with stage of disease and unfavourable clinical outcome (P less than 0.001). Thus, the proportion of positively reacting neoplasms increased as the stage progressed, tumours which had invaded regional lymph-nodes overexpressed p53 more frequently than localised carcinomas and an elevated level of p53 was associated with early relapse and death. In colorectal carcinoma p53 positivity was also linked with site and macroscopic configuration of the primary tumour and was most frequently expressed in carcinomas from the rectum and in ulcerative tumours. p53 overexpression was irrespective of tumour grade. Uniform negative reactivity with anti-p53 antibody was seen in normal epithelium adjacent to carcinoma, intestinal metaplasia, atrophic gastritis and in colonic adenomas. There was a good correlation between immunohistochemical staining on paraffin and frozen sections. These studies suggest that in gastric and colorectal carcinoma, immunohistochemical detection of p53 protein in routinely fixed tissue can be used along with other established parameters to assess prognostic outcome, especially to identify patients with poor short-term prognosis.     

Prognostic significance of cyclin E overexpression in laryngeal squamous cell carcinomas.

Cyclin E plays a pivotal role in the regulation of G1-S transition and relates to malignant transformation of cells. However, the clinical significance of cyclin E in patients with laryngeal squamous cell carcinoma (LSCC) remains unknown. We examined the expression of cyclin E in 102 patients with LSCC and analyzed its relation to clinicopathological parameters, cell proliferation, and clinical outcome. Cyclin E overexpression was observed in 54 cases (52.94%) of LSCC and was significantly correlated with the tumor site (P = 0.012), tumor size (P = 0.006), poor differentiation (P = 0.026), lymph node metastasis (P = 0.012), and advanced stage (P = 0.002). A positive correlation between the cyclin E expression and proliferative activity of tumor cells was found (r = 0.896; P < 0.0001). Kaplan-Meier analysis showed that shorter disease-free and overall survival was significantly associated with proliferating cell nuclear antigen (PCNA) overexpression and cyclin E overexpression. When PCNA and cyclin E are combined, the patients with both PCNA overexpression and cyclin E overexpression had the poorest prognoses when compared with the other cases. Additionally, in early stage (I-II) cases, cyclin E was also revealed to possess a significant prognostic role. By multivariate analysis, lymph node metastasis and cyclin E overexpression were independent prognostic factors for disease-free survival, and tumor size, lymph node metastasis, advanced stage, as well as cyclin E overexpression were independent prognostic factors for overall survival. These findings indicate that cyclin E overexpression is associated with unfavorable clinicopathological parameters and represents an independent marker for cell proliferation and prognosis of LSCC.     

Prognostic significance of p53 protein overexpression in betel- and tobacco-related oral oncogenesis

We have previously reported overexpression of p53 protein in tobacco-related oral dysplasia and squamous cell carcinoma (SCC) in the Indian population. A follow-up study was carried out to determine the prognostic significance of an accumulation of p53 protein during oral tumorigenesis. One hundred and two of 145 (70%) of oral SCCs and 39/75 (52%) of oral dysplasias showed overexpression of p53 protein, while only 3 of 107 (3%) normal oral tissues showed a detectable level of the protein. Follow-up studies of these patients suggest that an accumulation of p53 protein may be involved in the early phases of oral SCC development and indicate the predisposition of a particular premalignant lesion towards malignancy. In patients with premalignant lesions, the median transition time (premalignancy to malignancy) was significantly shorter in p53 positive cases than in p53 negative cases (p = 0.013). Among the oral cancer patients, univariate analysis showed that alteration in p53 expression was associated with significantly decreased disease-free survival. The p53 positive cases showed decreased median disease-free survival time (no recurrence/metastasis) compared with the p53 negative cases (p = 0.013), indicating that p53 accumulation may serve as a prognostic indicator in oral cancer patients. Int. J. Cancer (Pred. Oncol.) 79:370–375, 1998. © 1998 Wiley-Liss, Inc.     

Prognostic significance of p53 overexpression and mutation in colorectal adenocarcinomas.

The p53 tumour-suppressor gene is found altered in the majority of colorectal cancers. Lesions include allelic loss, mutation of the gene and overexpression of the p53 protein. All of these lesions have been analysed for prognostic significance, and whereas both mutation and allelic loss have been shown to be reasonably useful markers of prognosis, the utility of overexpression of the p53 protein is more ambiguous. Given that many authors use p53 overexpression as a marker for point mutation this issue is of some importance. We have therefore examined 100 colorectal carcinomas for mutation of the p53 gene, as well as overexpression of the p53 protein. Results show that whereas mutation of the p53 gene is associated with p53 overexpression, the degree of association depends, at least in part, upon the particular antibody used. Moreover, although mutation of the p53 gene does provide prognostic information, overexpression of the p53 protein, as detected with two antibodies, does not. These results suggest that immunohistochemistry is not a suitable alternative to direct detection of mutation in assessing prognosis in colorectal cancer patients.     

p53和cyclin E在尖锐湿疣中的表达及意义

目的 探讨ｐ５３和ｃｙｃｌｉｎＥ蛋白的表达与ＣＡ的相互关系及在ＣＡ中ｐ５３和ｃｙｃｌｉｎＥ两者表达的相关性。方法 利用ＨＰＶ６Ｂ／１１原位杂交显示人乳头状瘤病毒（ＨＰＶ）证实ＣＡ,及ＳＰ法免疫组化技术检测ｐ５３和ｃｙｃｌｉｎＥ蛋白。结果ＨＰＶ６Ｂ／１１在ＣＡ中阳性率为９１．７％,ｐ５３蛋白的表达阳性率为５８．３％。与正常包皮对照组有显著性差异（Ｐ〈０．０１）,而与生殖器鳞癌组无显著性差异（Ｐ〉０．     

Prognostic significance of cyclin E overexpression in resected non-small cell lung cancer

Cyclin E plays a pivotal role in the regulation of G1-S transition and relates to malignant transformation of the cells. However, the clinical significance of cyclin E expression in patients with non-small cell lung cancer remains unknown. We examined the expression of cyclin E in 242 resected non-small cell lung cancer in pathological stages I-IIIa and analyzed its relation to clinicopathological factors. Cylin E overexpressions were observed frequently in deeply invasive tumors. Multivariate analysis revealed that complete resection, pathological stage, and cyclin E expression were independent prognostic indicators. When cyclin E and proliferating cell nuclear antigen are combined, the cases negative for both had a significantly better prognosis than the other cases. We concluded that cyclin E overexpression relates to deeply invasive tumors and is correlated with poor prognosis. New therapeutic options may be provided by combination of cyclin E expression and proliferating cell nuclear antigen overexpression.     

Prognostic implications of p27 and cyclin E protein contents in malignant lymphomas.

The G1/S transition in the cell cycle is one of the checkpoints that can be deregulated in tumor development potentially causing increased proliferation and impaired capacity to arrest genetically damaged cells. The balance between activating and inhibitory molecules acting in the check point area seems to be critical and overexpression of cyclins and/or downregulation of the cdk inhibitors have been observed in many malignancies including lymphomas. In this review we have focused on two of the interplayers in the G1/S transition namely cyclin E and p27, and present the current knowledge of aberrations affecting these proteins in lymphomas as well as associations with clinico-pathological data including survival.     

细胞周期素E和P53蛋白在胃癌组织中表达及预后意义

目的 :研究细胞周期素E(cyclinE)和P53蛋白在胃癌组织中的表达水平及其与生物学行为和对预后的作用。方法 :应用免疫组化方法检测 1 2 8例胃癌组织中cyclinE和P53蛋白表达水平。 结果 :本组 1 2 8例中 ,cyclinE蛋白阳性 57例 ,占 44 .5 % ;P53蛋白阳性 67例 ,占 52 .3 % ,P53 +/cyclinE +者 48例 ,占 37.5 %。胃癌组织中cyclinE和P53蛋白表达水平与肿瘤大小、浸润深度、局部淋巴结转移、脉管侵犯和远处转移均相关。单因素生存分析显示 ,cyclinE阳性表达组五年生存率 (5 .3 % )显著低于cyclinE表达阴性组 (36 .6 % ,P <0 .0 0 1 ) ,P53蛋白表达阳性的病例五年生存率 (7.8% )显著低于P53表达阴性的病例 (2 2 .6 % ,P <0 .0 0 1 ) ,cyclinE和P53均阳性的病例五年生存率 (2 .3 % ) ,明显低于其他组的病例 (2 7.3 % ,P <0 .0 0 5)。COX模型多因素分析显示 ,cyclinE蛋白表达水平是独立的预后指标 ,P53蛋白表达水平不能作为独立的预后指标。结论 :CyclinE在胃癌中表达具有一定的预后意义 ,P53蛋白在胃癌中表达与肿瘤的生物学行为有关     

Synergistic induction of centrosome hyperamplification by loss of p53 and cyclin E overexpression

Centrosome hyperamplification and the consequential mitotic defects contribute to chromosome instability in cancers. Loss or mutational inactivation of p53 has been shown to induce chromosome instability through centrosome hyperamplification. It has recently been found that Cdk2-cyclin E is involved in the initiation of centrosome duplication, and that constitutive activation of Cdk2-cyclin E results in the uncoupling of the centrosome duplication cycle and the DNA replication cycle. Cyclin E overexpression and p53 mutations occur frequently in tumors. Here, we show that cyclin E overexpression and loss of p53 synergistically increase the frequency of centrosome hyperamplification in cultured cells as well as in tumors developed in p53-null, heterozygous, and wildtype mice. Through examination of cells derived from Waf1-null mice, we further found that Waf1, a potent inhibitor of Cdk2-cyclin E and a major target of p53's transactivation function, is involved in coordinating the initiation of centrosome duplication and DNA replication, suggesting that Waf1 may act as a molecular link between p53 and Cdk2-cyclin E in the control of the centrosome duplication cycle.     

组织蛋白酶D在肾盂输尿管移行细胞癌中表达的意义

目的：探讨组织蛋白酶D在上尿路移行细胞癌中表达的临床意义。方法：应用免疫组织化学ABC法，对组织蛋白酶D在43例肾盂、输尿管移行细胞癌中的表达进行检测。结果：肿瘤细胞阳性表达19例（44．2％）；间质细胞阳性表达14例（32．6％）。两表达与肿瘤分级、分期无显差异（P＞0．05）。间质细胞组织蛋白酶D阳性表达的患术后肿瘤复发明显高于阴性表达（P＜0．05），且5年生存期明显低于阴性表达（P＜0．05）。结论：上尿路移行细胞癌间质细胞组织蛋白酶D的检测，对术后肿瘤复发、生存期的判断具有一定的临床价值，可能用作判断预后的指标之一。     

Prognostic significance of p53 mutation and p53 overexpression in advanced epithelial ovarian cancer: a Gynecologic Oncology Group Study.

PURPOSE: The prognostic significance of p53 mutations and overexpression in advanced epithelial ovarian cancers was examined in primary tumors from 125 patients participating in a Gynecologic Oncology Group randomized phase III treatment protocol. PATIENTS AND METHODS: Mutational analysis of p53 was performed in RNA or genomic DNA extracted from frozen tumor. An immunohistochemistry assay was used to detect p53 overexpression in fixed tumor. RESULTS: There were 81 patients (74%) with a single mutation, three patients (3%) with two mutations, and 25 patients (23%) lacking a mutation in exons 2 to 11 of p53. Although most mutations occurred within exons 5 to 8, mutations outside this region were observed in 11% of patients. A mutation in exons 2 to 11 of p53 was associated with a short-term improvement in overall survival and progression-free survival. Adjusted Cox modeling demonstrated a 70% reduction in risk of death (P =.014) and a 60% reduction in risk of disease progression (P =.014) for women with such mutations. However, these striking risk reductions increased over time (P <.02) and eventually disappeared with longer follow-up. Overexpression of p53 was observed in 55 patients (100%) with only missense mutation(s), seven patients (32%) with truncation mutations, and eight patients (40%) lacking a mutation in exons 2 to 11. Overexpression of p53 was associated with tumor grade but not with patient outcome. CONCLUSION: Alterations in p53 are a common event in advanced epithelial ovarian cancer. A mutation in p53, but not overexpression of p53, is associated with a short-term survival benefit. Additional studies are required to define the roles that p53 plays in regulating therapeutic responsiveness and patient outcome.     

p53 and cyclin a protein expression in squamous carcinoma of the oesophagus

The aim of this study was to explore the relationship between p53 and cyclin A immunostaining in squamous carcinomas of the oesophagus. It has been shown that both these proteins are overexpressed in poorly differentiated endometrial carcinomas. Fifty oesophagectomy specimens were analysed for p53 and cyclin A immunoexpression. This was correlated with patient age and gender and tumor stage and grade. Forty-two percent of cases were p53 positive, while 94% of the squamous cancers expressed cyclin A protein. Neither protein showed any statistically significant correlation with clinicopathological parameters. This study has demonstrated that only 42% of oesophageal squamous carcinomas from South Africa express p53 protein, while the vast majority (94%) express cyclin A protein. Neither of these proteins showed any relationship to each other or any clinical feature or the tumor grade or stage.     

鼻咽癌p53蛋白表达与p53基因结构改变及mdm2蛋白表达的关系和意义

探讨影响ＮＰＣｐ５３蛋白表达的因素,Ｐ５３和ｍｄｍ２蛋白在ＮＰＣ发生中的变化和意义。方法采用免疫组化法检测ｐ５３和ｍｄｍ２蛋白、Ｓｏｕｈｅｒｎ杂交法检测Ｐ５３基因结构。     

Prognostic significance of p53 protein expression in early gastric cancer

Mutations of the p53 tumor suppressor gene have been associated with abnormalities in cell cycle regulation, DNA repair and synthesis, apoptosis, and it has been implicated in the prognosis of advanced gastric cancer. The aim of this study was to evaluate the occurrence of p53 gene mutation and its possible prognostic implications in early gastric cancer. In a retrospective study, we studied 80 patients with early gastric cancer treated surgically between 1982 and 2001. Mutation of p53 gene was investigated in surgical gastric specimens by immunohistochemistry, and results were analyzed in relation to gender, age, macroscopic appearance, size and location of tumor, presence of lymph nodes, Lauren’s histological type, degree of differentiation, and the 5-year survival. The expression of p53 was more frequent among the intestinal type (p = 0.003), the differentiated (p = 0.007), and the macroscopically elevated tumors (p = 0.038). Nevertheless, the isolated expression of p53 was not associated with the 5-year survival, or with the frequency of lymph node involvement. The degree of differentiation was detected as an independent factor related to the outcome of patients (0.044). Significantly shorter survival time was found in p53-negative compared with p53-positive patients, when considering the degree of differentiation of tumors, as assessed by Cox regression analysis (0.049). The association of p53 with the intestinal type, the degree of differentiation and morphological characteristics, may reflect the involvement of chronic inflammatory process underlying early gastric cancer. In this population sample, the expression of p53 alone has no prognostic value for early gastric cancer. However, the significant difference in p53 expression between subgroups of degree of differentiation of tumors can influence post-operative outcome of patients and may be related to possible distinct etiopathogenic subtypes.     

Prognostic impact of p53 protein overexpression in patients with node-negative lung adenocarcinoma

Prognostic value of p53 protein expression in node-negative lung adenocarcinoma is still controversy. The expression of p53 protein was examined immunohistochemically in lung adenocarcinoma using monoclonal antibody BP53-12. A total 131 cases of primary lung adenocarcinoma were examined. Relationship between expression of p53 protein and clinicopathologic factors were studied. Overexpression of p53 protein was found in 19 patients (14.5%). Univariate and multivariate analysis showed that overexpression of p53 protein was an independent prognostic factor in node-negative lung adenocarcinoma. p53 alteration could be a valuable predictor for prognosis in node-negative lung adenocarcinoma.     

Prognostic value of overexpression of p53 in human ovarian carcinoma patients receiving cisplatin

A major obstacle to the treatment of ovarian carcinoma is intrinsic/acquired resistance to cisplatin-based chemotherapy. The clinical significance of p53 overexpression in patients with ovarian carcinoma is still controversial. The aim of this study was to investigate the independent prognostic significance of p53 overexpression in patients with ovarian carcinoma who are treated with cisplatin. We retrospectively examined the overexpression of p53 in primary ovarian carcinoma, and its association with chemotherapeutic efficacy. One hundred and thirty four ovarian carcinomas were surgically removed from patients who received adjuvant cisplatin-based chemotherapy. Immunohistochemical analysis of p53 was performed using a DO7 antibody against the p53 protein in 134 ovarian carcinomas. The significance of p53 in the prognosis of patients with ovarian carcinomas was also examined by a survival analysis of mortality follow-up data covering the period from 1988 to 2001. Thirty-three tumors (25%) exhibited p53 overexpression. Overexpression of p53 in grade 2/grade 3 tumors was significantly higher than that seen in grade 1 tumors (P=0.0088, 0.0229). Patients with tumors who also showed overexpression of p53 had a significantly inferior response to chemotherapy compared with the patients with p53-negative tumors (P=0.04). Cox regression analysis revealed that p53 overexpression was prognostic for poor disease outcome after adjustment for FIGO stage, grade and residual tumor. These findings suggest that overexpression of p53 in ovarian carcinoma is associated with unfavorable clinical outcome in patients treated with cisplatin-based chemotherapy. Therefore, detection of p53 overexpression using the DO7 antibody may be considered as a predictive marker of chemoresistance for cisplatin in patients with ovarian carcinoma.     

人乳腺癌组织p53基因突变及过度表达的临床意义

应用聚合酶链反应－单链构象多态（ＰＣＲ－ＳＳＣＰ）分析和流式细胞术（ＦＣＭ），研究３０例患者乳膛癌组织Ｐ５３基因５￣８外显子的突变情况、Ｐ５３蛋白免疫组化检出情况、ＤＮＡ倍体及雌激素受体（ＥＲ）含量；并与各生物学参数进行了相关研究，以探讨Ｐ５３基因与乳腺癌发生、发展的关系。结果提示：１．全组１４例（４６．７％）发现Ｐ５３基因突变，其中１例为原位导管癌。２．Ｐ５３蛋白检出阳性率为５３．３％（１６／３     

Prognostic significance of thymidine phosphorylase and p53 co-expression in esophageal squamous cell carcinoma.

This study investigated the prognostic significance of thymidine phosphorylase (TP) and p53 expression in 96 surgically resected primary esophageal squamous cell carcinomas. Expression was assessed using immunohistochemical staining methods. Prognostic values were determined by multivariate analysis using Cox's proportional hazards model. Although TP expression was not correlated with p53 expression, it was associated with genetic alteration of the latter. In univariate analysis, TP expression emerged as a significant prognostic factor but p53 expression did not. However, in multivariate analysis, despite TP not being a significant independent predictor of survival, co-expression of TP together with p53 did represent a statistically significant prognostic factor.     

卵巢上皮性癌p53基因改变,蛋白过度表达及临床意义

目的：检测卵巢上皮性癌ｐ５３基因改变、蛋白过度表达，探讨其与临床病理和预后的关系。方法：应用ＡＢＣ免疫组化法检测５６例卵巢上皮性肿瘤ｐ５３蛋白表达，对其中４０例应用聚合酶链反应单链构象多态性（ＰＣＲＳＳＣＰ）溴乙锭染色法检测ｐ５３基因５～８外显子突变及杂合性缺失（ＬＯＨ）。结果：（１）ｐ５３蛋白表达阳性率：良性肿瘤０／１０；交界性肿瘤１／４；卵巢上皮性癌２２／４２（５２．３８％），浆液性与粘液性癌表达相似，且３例原发灶与转移灶表达一致。（２）ｐ５３基因突变率：良性肿瘤０／１０；交界性肿瘤１／３；卵巢上皮性癌１３／２７（４８．１５％），其中８例杂合型基因的病例中４例基因突变伴等位基因杂合性缺失。本研究１３例ｐ５３基因突变者中１２例ｐ５３蛋白过度表达。ｐ５３蛋白过度表达与卵巢上皮性癌组织学类型、临床分期及预后无关（Ｐ＞０．０５）。而与卵巢上皮性癌病理有关（Ｐ＜０００５）。结论：ｐ５３基因改变及蛋白过度表达在卵巢癌中较常发生，且与卵巢上皮性癌病理分级有关，这些改变可能是卵巢上皮性癌的早发事件，亦在卵巢上皮性癌的发生发展过程中起重要作用。