p53 status: an indicator for the effect of preoperative radiotherapy of rectal cancer.

BACKGROUND: Rectal carcinoma is a common malignancy, with a history of high local recurrence rates following surgery. In recent years. preoperative radiotherapy and refined surgical technique have improved local control rates. AIM: To investigate the relationship between expression of nuclear p53 protein and the outcome in rectal carcinoma, with and without short-term preoperative radiotherapy. MATERIAL: Specimens from 163 patients from the Southeast Swedish Health Care region included in the Swedish rectal cancer trial between 1987-1990. METHOD: New sections from the paraffin blocks of the preoperative biopsy and the surgical specimen were examined immunohistochemically using a p53 antibody (PAb 1801). RESULT: Expression of nuclear p53 protein was seen in 41% of the tumours. The p53 negative patients treated with preoperative radiotherapy had a significant reduction of local failure compared with the non-irradiated p53 negative patients (P = 0.0008). In contrast, p53 positive patients showed no benefit from preoperative radiotherapy. The interaction between p53 status and the benefit of radiotherapy was statistically significant (P = 0.018). CONCLUSION: Expression of nuclear p53 protein in rectal carcinoma seems to be a significant predictive factor for local treatment failure after preoperative radiotherapy. Further investigations are necessary to select patients for preoperative treatment based on analysis of the preoperative biopsies.     

Alteration of p53-binding protein 1 expression as a risk factor for local recurrence in patients undergoing resection for extrahepatic cholangiocarcinoma

P53-binding protein 1 (53BP1) is an early DNA damage response-protein that is rapidly recruited to sites of DNA double-strand breaks. The presence of 53BP1 nuclear foci can be considered as a cytologic marker for endogenous double-strand breaks reflecting genomic instability. This study aimed to clarify the early DNA damage response mediated by 53BP1 in tumor specimens of ductal resection margins and to elucidate its predictive value for clinically evident local recurrence at ductal stumps in 110 patients undergoing resection for extrahepatic cholangiocarcinoma. The ductal resection margin status was classified as negative (85 patients), positive with carcinoma in situ (14 patients), or positive with invasive carcinoma (11 patients). The nuclear staining pattern of 53BP1 was evaluated by immunofluorescence. TUNEL analysis was used to calculate apoptotic index. Ductal margin status was the only independent risk factor for local recurrence (P=0.001). The cumulative probability of local recurrence at 5 years was 10%, 40% and 100% in patients with negative ductal margins, positive with carcinoma in situ and positive with invasive carcinoma, respectively (P<0.001). Of the 14 tumor specimens of carcinoma in situ, 10 showed diffuse localization of 53BP1 in nuclei (53BP1 inactivation) and 4 showed discrete nuclear foci of 53BP1 (53BP1 activation). All 11 tumor specimens of invasive carcinoma showed 53BP1 inactivation. Apoptotic index was markedly decreased in tumor specimens with 53BP1 inactivation compared to those with 53BP1 activation (median index, 0% vs. 22%; P<0.001). Among 14 patients with residual carcinoma in situ, the cumulative probability of local recurrence was significantly higher in patients with 53BP1 inactivation than in patients with 53BP1 activation (60% vs. 0% at 5 years; P=0.020). In conclusion, after resection for extrahepatic cholangiocarcinoma, clinically evident local recurrence at ductal stumps is closely associated with 53BP1 inactivation and decreased apoptosis.     

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.     

p53 overexpression impacts on the prognosis of laryngeal squamous cell carcinomas

Objectives: To investigate the prognostic implications of p53 expression in the surgical margins of laryngealsquamous cell carcinomas. Methods: Thirty one patients with T3-4N0M0 cancers with pathologically negativemargins were analyzed by immunohistochemistry (IHC) to detect expression of p53. Results: The p53 positiverates by IHC in the surgical margin were 16.1% (5/31). In the p53 positive margin group, the recurrent ratewas higher than those without (80% vs 19.2%, P = 0.006). Also, the median free of disease period in the p53positive margin group was shorter than other group (22.2 vs 47.8 months, P < 0.0001). Conclusions: We foundthat the overexpression of p53 can serve a prognostic role for both recurrence and disease-specific mortality inhead and neck squamous cell carcinoma. p53 expression could stratify patients, in an easy and inexpensive way,according to their risk of local or regional recurrence.     

Negative p53/positive p21 immunostaining is a predictor of favorable response to chemotherapy in patients with locally advanced bladder cancer.

The relationship between clinical response to DNA-damaging drugs and p53 and p21 status in patients with locally advanced transitional cell carcinoma (TCC) of the bladder was assessed. The response to intraarterial chemotherapy (IAC) comprising 100 mg / m(2) of cisplatin (CDDP) and 40 mg / m(2) of pirarubicin (THP) and the prognosis were assessed in 23 patients (the mean follow-up period was 19 months). The p53 gene status of tumors was analyzed at exons 5 - 8 using polymerase chain reaction-single strand conformation polymorphism analysis in 19 patients, and paraffin-embedded tumor sections were immunostained for p53 and p21 in 23 patients. The overall objective response rate (incidence of good responders) was 70%. The negative p53 group (n = 17) showed a significantly higher objective response rate than the positive p53 group (n = 6) (82% vs. 33%; P = 0.045). The p53 gene status or p21 staining status was not significantly associated with responsiveness. When the p53 and p21 immunostaining results were combined, good responders were more accurately predicted than by p53 staining status alone; the negative p53 / positive p21 group (n = 12) showed an objective response rate of 92%, which was significantly higher than that of the positive p53 and / or negative p21 group (45%, n = 11) (P = 0.027). Cause-specific survival of the negative p53 group was significantly superior to that of the positive p53 group (P = 0.015). Negative p53 / positive p21 immunostaining is a possible predictor of favorable chemotherapeutic response in patients with TCC of the bladder.     

Negative p53/Positive p21 Immunostaining Is a Predictor of Favorable Response to Chemotherapy in Patients with Locally Advanced Bladder Cancer

The relationship between clinical response to DNA-damaging drugs and p53 and p21 status in patients with locally advanced transitional cell carcinoma (TCC) of the bladder was assessed. The response to intraarterial chemotherapy (IAC) comprising 100 mg/m² of cisplatin (CDDP) and 40 mg/m² of pirarubicin (THP) and the prognosis were assessed in 23 patients (the mean follow-up period was 19 months). The p 53 gene status of tumors was analyzed at exons 5–8 using polymerase chain reaction-single strand conformation polymorphism analysis in 19 patients, and paraffinembedded tumor sections were immunostained for p⁵³ and p²¹ in 23 patients. The overall objective response rate (incidence of good responders) was 70%. The negative p53 group ( n =17) showed a significantly higher objective response rate than the positive p53 group ( n =6) (82% vs. 33%; P =0.045). The p 53 gene status or p21 staining status was not significantly associated with responsiveness. When the p53 and p21 immunostaining results were combined, good responders were more accurately predicted than by p53 staining status alone; the negative p53/positive p21 group ( n =12) showed an objective response rate of 92%, which was significantly higher than that of the positive p53 and/or negative p21 group (45%, n =11) ( P =0.027). Cause-specific survival of the negative p53 group was significantly superior to that of the positive p53 group ( P =0.015). Negative p53/positive p21 immunostaining is a possible predictor of favorable chemotherapeutic response in patients with TCC of the bladder.     

Significant effects of preoperative intraluminal brachytherapy on the survival rate after resection of rectal carcinoma

We investigated whether or not preoperative intraluminal brachytherapy (IBT) contributes to a prolongation of the survival after resection of rectal carcinoma. Eighty-five patients with middle and lower rectal carcinoma with penetration into or through the rectal wall were treated with preoperative IBT (30 Gy) and radical resection. The patients were divided into the major effect group (n=59, proportion of remaining viable cells less than 25% of the background stroma) and the minor effect group (n=26, proportion of viable cells over 25%). The major effect group had more down-staged tumors, and a lower rate of positive nodes. Local recurrence rate, distant recurrence rate, and survival rate of the major effect group were 9% (31% in the minor effect group), 15% (55% in minor group) and 74% (36% in minor group), respectively (all parameters: p<0.05). Multivariate analysis indicated that nodal involvement, tumor depth, and proportion of viable cells were the prognostic factors. Preoperative IBT affected not only the tumor morphology but also the prognosis. Our criterion of the proportion of residual viable cells was significantly correlated to the patients' survival. The analyses revealed the positive effects of IBT on the prognosis of rectal cancer.     

Correlation of p53 and the proto-oncogene eIF4E in larynx cancers: prognostic implications

p53 abnormalities constitute the most frequent genetic alterations identified in larynx cancers. p53 overexpression in histologically "tumor-free" surgical margins correlates with a high recurrence rate. However, only 50-60% of tumors overexpress p53. The tumor marker eIF4E is overexpressed in 100% of larynx cancers, and overexpression of eIF4E in histologically "tumor-free" margins predicts a significantly higher recurrence. We undertook this study to correlate the expression of p53 and eIF4E in the tumors and surgical margins of squamous cell cancers of the larynx and to determine their prognostic value. A retrospective analysis was performed on 54 patients who underwent surgery for squamous cell cancers of the larynx. Patient and tumor characteristics were reviewed, and the time to recurrence was noted. Paraffin-embedded sections from the tumors and surgical margins were immunostained with antibodies to eIF4E and p53, and a qualitative analysis was performed. All 54 patients (100%) overexpressed eIF4E in the primary tumor, whereas 25 of 53 patients (47%) were p53 positive. Thirty-two of the 54 patients (59%) had eIF4E-positive margins. All 6 of 53 patients (11%) with p53-positive margins also overexpressed eIF4E in the margins. There was a significant correlation between p53 and eIF4E being positive in the margins (Spearman's correlation coefficient, P = 0.03). Twenty-one of the 25 patients (84%) that recurred, including the 6 patients with p53-positive margins, had eIF4E-positive margins. Hence, although the univariate analysis showed that nodal status and both eIF4E and p53 expression in the margins were significant predictors of recurrence (P < 0.05), in the multivariate analyses only nodal status (P < 0.001) and eIF4E in the margins (P < 0.001) were significant predictors of recurrence. Kaplan-Meier analysis demonstrated that the disease-free intervals for eIF4E-positive margins were significantly shorter than eIF4E-negative margins (P = 0.0007). There was no additional effect to the combination of positive p53 and eIF4E margins (P = 0.21). The overexpression of eIF4E in the margins appears to be a more sensitive indicator of recurrence and may be an earlier event in the process of tumorigenesis than p53.     

EXPRESSION OF FRAGILE HISTIDINE TRIAD AND P53 IN NON-SMALL CELL LUNG CANCER

Objective： To investigate the expression offragile histidine triad （FHIT） and p53 protein in non-small cell lung cancer （NSCLC） and explore the relationship between their expressions and the clinicopathological features. Methods： FHIT protein and p53 protein were detected by immunohistochemistry in 76 cases of NSCLCs and matched normal lung tissues. Results： Fifty-one cases （67.1%） showed negative expression of FHIT （apparent reduction or loss） and thirty-seven cases （48.7%） showed p53 positive expression （overexpression）. The difference was significant （P=0.04）. However, there was no significant difference in FHIT expression between the p53-positive group and the p53-negative group （64.9% versus 69.2%, P=0.686）. The negative rate of FHIT protein expression was higher in squamous cell carcinoma than in adenocarcinoma, in moderately and poorly differentiated carcinoma than in well-differentiated carcinoma, and in cases with smoking history than in cases without smoking history （P〈0.05）. There was no relationship between FHIT expression and clinical stage or lymph node metastasis. The negative FHIT expression was not an independent predictor of overall survival （P=0.338）. Conclusion： The frequency of negative expression of FHIT protein is higher than that of positive expression of p53 in NSCLCs. The negative expression of FHIT is independent of the expression of p53. The change of expression of FHIT may play a role in the smoking related lung tumorigenesis while it may have no relationship with the progress of NSCLC or prognosis of the patients.     

Serum p53 antibody is a useful tumor marker in superficial esophageal squamous cell carcinoma

BACKGROUND: Patients with superficial (mucosal or submucosal) esophageal carcinoma (SEC) have significantly better survival rates than patients with advanced carcinoma. Some patients with advanced esophageal carcinoma have been reported to test positive for serum p53 antibodies (Abs). Because very few patients with superficial carcinoma have been examined, the aim of this study was to evaluate the clinical significance of serum p53-Abs in patients with superficial esophageal squamous cell carcinoma (SESCC). METHODS: Thirty-five consecutive patients with SESCC were studied for serum p53-Abs by enzyme-linked immunoabsorbent assay before and after treatment. The clinicopathologic features of p53 seropositive and p53 negative patients were compared. The relation between the presence of serum p53-Abs and p53 immunoreactivity of the resected specimens was examined. Three tumor markers (squamous cell carcinoma antigen [SCC-Ag], CYFRA21-1, and carcinoembryonic antigen [CEA]) were assessed to compare their sensitivities with serum p53-Abs. RESULTS: Fourteen of 35 patients (40%) were p53 seropositive. Relatively few patients tested positive for the other tumor markers: CEA, 11.4%; SCC-Ag, 14.3%; CYFRA21-1, 5.7%. There were no significant correlations between clinicopathologic features and p53 seropositivity except for tumor location. A strong correlation between p53 immunostaining and the presence of serum p53-Abs was observed (P = 0.003). Of the 14 patients with seropositive results, 12 turned seronegative after resection, and the other 2 experienced disease recurrence. CONCLUSIONS: Surveillance of serum p53-Abs is superior to the three tumor markers for detecting SESCC. This serum marker is also useful for the detection of p53 protein overexpression and for the monitoring of residual tumor cells.     

The Prognostic Significance of P53 Expression for Survival and Local Control in Rectal Carcinoma Treated with Surgery and Postoperative Radiotherapy

Purpose: To investigate whether p53 immunoreactivity is a prognostic factor for survival and pelvic control in rectal carcinoma treated with surgery and postoperative radiotherapy.Methods and Materials: From 1981 through 1989, 146 patients with rectal carcinoma received postoperative radiotherapy and were followed for at least 5 years or until death. The specimens of 123 of these 146 patients could be retrieved and examined immunohistochemically for p53 expression. The prognostic value for survival and pelvic control of p53 expression and other patient and treatment factors was examined by univariate and multivariate analyses.Results: p53 expression has no prognostic significance for overall survival in this group of 123 patients. The only prognostic factor for survival in this material is tumor stage (p < 0.01). The actuarial pelvic recurrence rates of p53− and p53+ cases are different in favor of the p53− ones. In the univariate analysis this difference is significant (p = 0.05). However, in the multivariate analysis the influence of p53 expression, additional to stage, becomes nonsignificant (p = 0.10). This indicates that p53 expression is not a strong independant prognostic factor for pelvic recurrence. In the multivariate analysis stage turns out to be the only predictor of pelvic recurrence (p = 0.03).When only recurrences inside the radiation field are considered, there is no difference between p53+ and p53− cases.Conclusion: Based on this material, we have found no convincing evidence that p53 expression is an important predictor of survival or local control in rectal cancer treated with surgery and postoperative radiotherapy. We have found no evidence that possible differences in radiosensitivity between p53+ and p53− tumors have clinical significance for this group of patients.     

Stomal recurrence in patients with T1 glottic cancer after salvage laryngectomy for radiotherapy failures: role of p53 overexpression and subglottic extension

The role of p53 overexpression in the development of stomal recurrence was studied in patients with T1 glottic cancer who had undergone salvage laryngectomy after primary radiotherapy failure (first recurrence). The role of subglottic extension of the recurrent tumor in the development of stomal recurrence was also studied. One hundred fourteen patients with T1 squamous cell carcinoma of the glottic larynx were irradiated with curative intent. A local recurrence (first recurrence) developed in 23 patients (20%), and salvage laryngectomy was performed for 20 of these patients. No postlaryngectomy radiation therapy was included in the treatment of recurrences. Several risk factors thought to be significant in the development of stomal recurrence were analyzed in these 20 patients. Prognostic factors analyzed include: p53 overexpression in the preradiation biopsy specimen, subglottic extension of the first recurrence, thyroid cartilage and lymph node involvement at the time of first recurrence, emergency tracheostomy performed before salvage laryngectomy, and the laryngectomy procedure performed for first recurrence. Presence of p53 protein in the preradiation biopsy specimen of laryngeal cancer did not show any adverse effect on the development of stomal recurrence. Stomal recurrence developed in 27% of patients with positive biopsies and in 20% of patients with negative biopsies (p = 1.00). Subglottic extension of the first recurrence was associated with an increased incidence of stomal recurrence. Rates of stomal recurrence were 6% in patients without subglottic extension and 100% in patients with subglottic extension (p = 0.001). All other risk factors studied showed no effect on stomal recurrence. In this study, p53 overexpression showed no effect on the development of stomal recurrence after salvage laryngectomy in patients with T1 glottic cancer. Conversely, subglottic extension of the recurrence was found to be strongly associated with stomal recurrence. All other factors analyzed showed no effect on stomal recurrence.     

喉癌切缘组织中p53 p21及PCNA表达及其与肿瘤复发的关系

目的:研究早期喉癌手术切缘阴性组织中p53、p21及PCNA表达的相关性及其与肿瘤复发的关系。方法:选取唐山市协和医院2004年1月至2010年12月间92例早期喉癌患者为研究对象,采用免疫组织化学法联合检测肿瘤及其切缘组织中p53、p21及PCNA的表达情况。电话随访2年以上,对患者生存及肿瘤复发情况进行观察。结果:p53、p21及PCNA蛋白在喉癌组织中的表达与肿瘤的分级及分期无关。92例喉癌患者术后2年内有16例出现复发,复发率为17.39%。喉癌阴性切缘复发和未复发标本中p53、p21及PCNA蛋白表达阳性的切缘复发率分别为50.00%、34.21%和33.33%,明显高于p53、p21及PCNA蛋白表达阴性的切缘（8.33%、5.56%和9.68%）。经统计学分析,喉癌复发标本3种蛋白切缘阳性率明显高于未复发标本,均有显著性差异（P＜0.01）。此外,喉癌阴性切缘组织中p53与p21蛋白的表达有明显的相关性,PCNA的表达与p21的表达亦有明显的相关性。结论:早期喉癌手术病理阴性切缘组织中的p53、p21及PCNA是患者预后的重要生物学标志,联合检测喉癌切缘组织中p53、p21及PC? NA的表达有望作为预测喉癌复发的指标。      

喉癌组织中p21、Yes相关蛋白的表达情况与喉癌患者术后复发的关系

目的 探讨喉癌组织中p21蛋白、Yes相关蛋白(YAP)的表达情况与喉癌患者术后复发情况的关系.方法 将118例喉癌术后患者根据复发情况分为复发组(n=47)、非复发组(n=68)、失访患者(n=3).比较复发组与非复发组患者喉癌组织中p21、YAP蛋白的阳性表达情况,并对喉癌患者术后复发的影响因素进行分析.结果 复发...     

一种从骨巨细胞瘤组织中纯化破骨细胞的简单方法

目的从人骨巨细胞瘤组织中分离纯化及鉴定破骨细胞。方法我们利用0．25％胰酶-EDTA和Ⅰ型胶原酶从人骨巨细胞瘤组织中纯化出大量破骨细胞，并进行表型特征的鉴定：包括抗酒石酸酸性磷酸酶染色(TRAP染色)，采用RT-PCR方法检测降钙素受体、组织蛋白酶K和破骨细胞分化因子受体(RANK)表达。结果该方法所得细胞纯度可达79．7％，具有破骨细胞表型特征。结论该方法所得破骨细胞可用于生化和分子生物学研究，是进行骨代谢研究较好的破骨细胞来源。     

病理学切缘和以p53与eIF4E为指标的分子切缘预测喉癌患者预后

目的探讨病理学切缘和以p53、eIF4E为指标的分子切缘在预测喉癌患者预后中的价值。方法选择了253例喉癌患者进行病理学切缘研究，在以上病理学阴性切缘中选择67例，应用免疫组化方法检测p53、eIF4E蛋白的表达以进行分子切缘研究。结果1．病理学切缘、p53切缘、eIF4E切缘的阳性率分别是20．2％，19．4％和32．8％；2．阳性切缘患者的复发率高于切缘阴性者，包括病理学切缘(70．6％vs35．1％，P=0．0000)、p53切缘(69．2％vs33．3％，P=0．018)、eIF4E切缘(63．6％vs28．90A，P=0．018)；而切缘阳性者5年累积生存率低于切缘阴性者，包括病理学切缘(37．52％vs64．37％，P=0．0023)、p53切缘(24．62％vs75．69％，P=0．0012)、eIF4E切缘(43．31％vs77．52％，P=0．0006)。结论病理学切缘和以p53、eIF4E为指标的分子切缘阳性者的预后比切缘阴性者差，而p53和eIF4E可以从病理学切缘阴性者中发现预后更差的患者，并且eIF4E可能是优p53的分子指标。     

Predictive value of vascular endothelial growth factor-C expression for local recurrence of rectal carcinoma

Vascular endothelial growth factor-C (VEGF-C) is considered to be a specific factor promoting lymphangiogenesis. There have been reports of a positive correlation between local recurrence of rectal carcinoma and lymphatic invasion by the tumor. The aim of this study was to determine the clinical significance of VEGF-C expression for identifying lymphangiogenesis as a predictor of the local recurrence of rectal carcinoma. One hundred surgical specimens of rectal carcinoma from patients with (n=26) or without (n=74) local recurrence were studied. VEGF-C protein expression was assessed immunohistochemically. The correlations between VEGF-C expression, various clinicopathologic factors, the microscopic lymphatic vessel density (MLVD), and lymphatic invasion were studied. The MLVD (determined by immunohistostaining for D2-40) was significantly higher in VEGF-C positive tumors than VEGF-C negative tumors. VEGF-C positivity was only correlated with lymphatic involvement. Moreover, multivariate analysis showed that VEGF-C protein expression was an independent risk factor for the local recurrence of rectal carcinoma, and patients with VEGF-C positive tumors had a significantly worse prognosis than those with VEGF-C negative tumors. Expression of VEGF-C may be a good predictor of the local recurrence of rectal carcinoma and may also be a useful prognostic indicator.     

Concurrent abnormal expression of ERBB-2, EGFR,and p53 genes and clinical disease progression of breast carcinoma

Metastatic phenotype in human solid tumors is believed to follow stochastic acquisition of structural genetic aberrations-so-called multistep tumor progression. We tested this hypothesis in breast carcinoma by immunostaining 89 stage-heterogeneous cases for the products of three genes (p53, ERBB-2, and EGFR) which are frequently altered in this tumor system. Variable relationships were observed between advanced disease stage and immunostaining for individual gene products (ERBB-2 - p = 0.05, EGFR - p = 0.02, p53 - p = 0.12, Chi Square test). Regional or distant metastases at presentation correlated with multiple oncogene/tumor suppressor gene expression abnormalities: node negative - 59% none positive, 29% one positive, 12% two or more positive, vs. node positive - 37% none positive, 23% one positive, 39% two or more positive (p = 0.01). Only 2/12 (17%) of tumors with distant metastases at presentation were negative for abnormal expression of any of these gene products, and 7/12 (58%) were positve for two or three. Among axillary node negative patients who developed recurrences, 67% exhibited staining for at least one gene product, compared to only 27% of those without recurrences (p = 0.02). All 5 cases with abnormal staining for each gene product had regional or distant metastases at presentation and recurred. In multivariate analysis, individual expression of p53 outweighed expression of ERBB-2 and EGFR in correlation with outcome. These data suggest clinical neoplastic progression of breast carcinomas correlates with cumulative genetic events detectable by protein expression. Short term recurrence, however, may correlate more closely with abnormal expression of p53 than with EGFR or ERBB-2.     

病理学切缘和以p53与eIF4E为指标的分子切缘预测喉癌患者预后(英文)

目的探讨病理学切缘和以 p53、eIF4E 为指标的分子切缘在预测喉癌患者预后中的价值。方法选择了253例喉癌患者进行病理学切缘研究,在以上病理学阴性切缘中选择67例,应用免疫组化方法检测 p53、eIF4E 蛋白的表达以进行分子切缘研究。结果 1.病理学切缘、p53切缘、eIF4E 切缘的阳性率分别是20.2%,19.4%和32.8%;2.阳性切缘患者的复发率高于切缘阴性者,包括病理学切缘(70.6% vs 35.1%,P=0.0000)、p53切缘(69.2% vs 33.3%,P=0.018)、eIF4E 切缘(63.6% vs 28.9%,P=0.018);而切缘阳性者5年累积生存率低于切缘阴性者,包括病理学切缘(37.52% vs 64.37%,P=0.0023)、p53切缘(24.62% vs75.69%,P=0.0012)、eIF4E 切缘(43.31% vs 77.52%,P=0.0006)。结论病理学切缘和以 p53、eIF4E 为指标的分子切缘阳性者的预后比切缘阴性者差,而 p53和 eIF4E 可以从病理学切缘阴性者中发现预后更差的患者,并且 eIF4E 可能是优 p53的分子指标。     

Mutant p53 protein overexpression in women with ipsilateral breast tumor recurrence following lumpectomy and radiation therapy

BACKGROUND: The p53 tumor suppressor gene encodes a nuclear phosphoprotein that is thought to be important to cell cycle regulation and DNA repair and that also may regulate induction of apoptosis by ionizing radiation. Somatic p53 gene mutations occur in 30-50% of breast carcinomas and are associated with poor prognosis. Mutations in the p53 gene result in prolonged stability of the protein that can be detected by immunohistochemical techniques. In a matched case-control study of breast carcinoma patients with ipsilateral breast tumor recurrence (IBTR) following lumpectomy and radiation therapy, the authors investigated the frequency and prognostic significance of somatic p53 mutations as well as the clinical characteristics of patients with these mutations. METHODS: Between 1973 and 1995, there were 121 breast carcinoma patients with IBTR following lumpectomy and radiation therapy, and the authors identified 47 patients in whom the paraffin embedded tissue blocks from the primary breast tumors were available for further molecular analysis. Forty-seven control breast carcinoma patients from the breast carcinoma data base were individually matched to the index cases who did not have IBTR for age, treatment date, follow-up, histology, margin status, radiation dose, and adjuvant treatment. Immunohistochemistry using a monoclonal antibody to mutant p53 protein was used to determine mutant p53 protein overexpression in breast tumors and appropriately scored. RESULTS: A total of 12 of 47 tumor specimens (26%) from index patients with breast tumor relapses demonstrated mutant p53 protein overexpression, whereas only 4 of 47 specimens from controls (9%) demonstrated high mutant p53 immunoreactivity (P = 0.02). The authors found that 9 of 23 patients (39%) with early breast tumor recurrences (recurrences within 4 years of diagnosis) had overexpression of mutant p53 protein, whereas only 1 of 23 control cases (4%) had high mutant p53 protein immunoreactivity (P = 0.003). In contrast, index cases from patients with late breast tumor relapses (more than 4 years after diagnosis), which are more likely to represent de novo breast tumors, and control cases from the breast carcinoma data base without IBTR had similar levels of mutant p53 protein overexpression (P = not significant). The 10-year distant disease free survival for patients with mutant p53 protein was 48%, compared with 67% for breast carcinoma patients without detection of mutant p53 protein (P = 0. 08). The authors found that 13 of 14 primary breast tumors (93%) with mutant p53 protein overexpression were estrogen receptor negative (P = 0.01) and 11 of 14 (79%) were progesterone receptor negative (P = not significant). CONCLUSIONS: In a matched case-control study, overexpression of mutant p53 protein has prognostic significance with respect to IBTR following lumpectomy and radiation therapy. Breast tumors with p53 mutations are generally estrogen receptor negative and are associated with compromised distant disease free survival.