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 value of p53 overexpression in bladder tumors treated with Bacillus Calmette-Guerin

Bacillus Calmette-Guerin intravesical therapy is the standard treatment of superficial bladder tumors at high risk of recurrence and progression to muscle-invasion disease. To date, there is no well established predictive factor of response to Bacillus Calmette-Guerin intravesical therapy. The prognostic value of p53 overexpression in bladder tumors is controversial. Most investigators have found no correlation between p53 status assessed before Bacillus Calmette-Guerin intravesical therapy and patient outcome. On the other hand, it is acknowledged that the persistence of p53 overexpression after Bacillus Calmette-Guerin intravesical therapy is predictive of progression in patients treated for carcinoma in situ. Since conflicting data have been reported, further evaluation of the impact of p53 overexpression in patients treated with Bacillus Calmette-Guerin intravesical therapy for bladder carcinoma is required.     

Prognostic value of p53 overexpression in bladder tumors treated with Bacillus Calmette-Guerin

Bacillus Calmette-Guerin intravesical therapy is the standard treatment of superficial bladder tumors at high risk of recurrence and progression to muscle-invasion disease. To date, there is no well established predictive factor of response to Bacillus Calmette-Guerin intravesical therapy. The prognostic value of p53 overexpression in bladder tumors is controversial. Most investigators have found no correlation between p53 status assessed before Bacillus Calmette-Guerin intravesical therapy and patient outcome. On the other hand, it is acknowledged that the persistence of p53 overexpression after Bacillus Calmette-Guerin intravesical therapy is predictive of progression in patients treated for carcinoma in situ. Since conflicting data have been reported, further evaluation of the impact of p53 overexpression in patients treated with Bacillus Calmette-Guerin intravesical therapy for bladder carcinoma is required.     

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 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.     

Prognostic value of p53 expression in hormone receptor-positive and human epidermal growth factor receptor 2-negative breast cancer patients receiving neoadjuvant chemotherapy

Breast Cancer Research and Treatment - The aim of this study was to determine whether the outcome to neoadjuvant chemotherapy (NAC) can be predicted by analyzing p53 expression in hormone receptor...     

Prognostic value of splenic volume in hepatocellular carcinoma patients receiving transarterial chemoembolization

BackgroundLiver function is a key determinant for the survival of hepatocellular carcinoma (HCC) patients receiving transarterial chemoembolization (TACE). However, establishing robust prognostic indicators for liver insufficiencies and patient survival remains an unmet demand. This retrospective study evaluated the prognostic value of splenic volume (SV) in HCC patients undergoing TACE.MethodsA total of 67 HCC patients who underwent at least two consecutive TACE procedures were retrospectively included in this study. Comprehensive clinical information and follow-up data were collected, and the SV was measured based on dynamic contrast enhanced images. Risk factors of SV enlargement were assessed. The prognostic value of SV on survival was analyzed and compared with Child-Pugh (CP) classification and albumin-bilirubin (ALBI) grade.ResultsThe baseline SV was 299.74±143.63 cm³, and showed a moderate and statistically significant correlation with CP classification (R=0.31, P<0.05). The SV increased remarkably after the first and second TACE procedures (330.16±155.38 cm³, P<0.01, and 355.63±164.26 cm³, P<0.01, respectively). In survival analysis, the optimal cut-off value of SV was determined as 373 cm³ using X-tile software, and the patients were divided into the small SV group and the large SV groups accordingly. Based on the pre-TACE SV, the median overall survival (mOS) for patients in the small SV group and the large SV group was 458 days and 249 days, respectively (P<0.05). After the first and second TACE, the mOS in the small SV group and the large SV group were 454 vs. 266 days (P<0.05) and 526 vs. 266 days (P<0.05), respectively. No prognostic value of CP classification and ALBI grade was identified for these patients. Furthermore, there were no significant differences between the small and large SV groups in age, tumor stage, and ALBI grade, except for CP classification (P<0.05).ConclusionsSV was correlated with CP classification and was a robust predictor for HCC patients undergoing TACE treatment.     

Prognostic value of human kallikrein 10 expression in epithelial ovarian carcinoma.

PURPOSE: Human kallikrein 10 (hK10; also known as the normal epithelial cell-specific 1 gene and protein) is a secreted serine protease, which belongs to the human kallikrein family. It has been reported that hK10 is down-regulated in breast and prostate cancer cell lines and that it may function as a tumor suppressor. Recently, we developed a highly sensitive and specific immunoassay for hK10 and found that this protein is abundantly expressed in ovarian tissue. In this study, we measured quantitatively hK10 levels in ovarian cancer cytosolic extracts and evaluated the prognostic value of this biomarker in ovarian cancer. EXPERIMENTAL DESIGN: Specimens from eight normal ovarian tissues, eight ovarian tissues with benign disease, and 182 ovarian tumors were investigated. RESULTS: hK10 concentration in ovarian tumor cytosols ranged from 0 to 84 ng/mg of total protein, with a median of 2.6. This median was highly elevated in comparison with normal and benign ovarian tissues (P < 0.001). A cutoff of 1.35 ng/mg was selected to categorize tumors as hK10 high and hK10 low. With chi(2) test and Fisher's exact test, high concentration hK10 was found to be associated with advanced disease stage, serous histological type, suboptimal debulking, and large residual tumor (>1 cm; all P < 0.05). hK10 status was additionally correlated with clinical outcome, including progression-free (PFS) and overall survival (OS) using the Cox model. In univariate analysis, we found that patients with hK10 high tumors were more likely to die and relapse, in comparison with patients with hK10 low tumors (hazards ratios for PFS and OS were 1.93 and 2.42, respectively; P < 0.05). Although this correlation disappeared after the entire patient population was subjected to multivariate analysis, it remained significant in the subgroup of patients with stage III/IV ovarian cancer (hazards ratios for PFS and OS were 1.98 and 2.12, respectively; P < 0.05). CONCLUSIONS: Our results indicate that hK10 is a new, independent, unfavorable prognostic marker, especially for late-stage ovarian cancer.     

Prognostic value of the flow cytometric DNA index in human ovarian carcinoma

Flow cytometric measurements were done on 51 ovarian carcinoma specimens collected from consecutive patients in a prospective study. The ploidy status was related to the course of the disease. The tumors from 26 (52%) of 50 evaluable patients had DNA aneuploidy. Patients with diploid tumors were more often considered disease-free after initial operation (P less than 0.01). Patients with aneuploid tumors had a more aggressive course of the disease in all respects of comparison. The median survival of patients with diploid tumors was 18 months as compared to 8 months for those with aneuploid tumors (P less than 0.0005). Flow cytometric DNA measurements give important prognostic information and such analyses should be included in future clinical trials. Through the development of high-speed instrumentation they also may become feasible in routine clinical work.     

Prognostic value of PCNA and mutant p53 expression in laryngeal squamous cell carcinoma

The objective of this study was to investigate the prognostic significance of p53, and proliferative cell nuclear antigen (PCNA) in laryngeal squamous cell carcinoma (LSCC). Sixty pathologic specimens from the patients with LSCC were examined for the expression of the p53 and PCNA, with complete follow-up data. Sixty-three percent of the cases displayed nuclear p53 overexpression. There was a correlation between p53 overexpression and histological grades (p = 0.03), and localization site (p = 0.05). Median of PCNA index was 42.2 (range 5.9 to 85.2). There was no difference between the p53 overexpression group and the normal group in proliferative activity determined by PCNA (p = 0.73). In univariate analyses, localization site, grade, stage, invasion pattern, lymph node status, were significant factors in estimating disease free survival (DFS). Grade was the most important factor affecting recurrence (p = 0.002). In multivariate analyses, grade was the only significant predictor for DFS (p = 0.001). Grade (p = 0.001) and invasion pattern (p = 0.03) were found to be significant predictors of overall survival. In conclusion, the histological grade was the most reliable important prognostic factor. Further studies are necessary to facilitate understanding of the mechanisms of laryngeal carcinogenesis.     

Prognostic value of hormonal receptors, p53, ki67 and HER2/neu expression in epithelial ovarian carcinoma

OBJECTIVE: The role of molecular and biological factors in ovarian cancer is controversial. We investigated the levels of the estrogen (ER) and progesterone (PR) receptors, HER2/neu, p-53 and Ki 67 in patients with advanced ovarian cancer and correlated the results with the clinical course in order to define their predictive or prognostic significance. METHODS: Paraffin-embedded tumor tissues from 72 patients with ovarian cancer treated from 1999 to 2003 were analyzed. Overexpression of C-erb-B2 was defined as herceptest ++/+++ and positive fluorescence in situ hybridization (FISH) or herceptest +++/+++. Positivity for ER and PR was determined by > or =10% of the cellular membranes immunostained. Statistical analysis was performed to evaluate the prognostic impact of the molecular markers. RESULTS: 49 of the 72 patients were ER + (68%) and 36 PR + (50%). In 45 patients (62.5%) expression of p53 was > or =10%. Overexpression of C-erb-2 was found in 4 tumor samples (5%). A Ki67 labelled nuclear area >30% was found to be associated with a higher rate of complete response (chi(2); p=0.05). None of the biological markers were significantly associated with progression free survival (PFS). By multivariate analysis residual tumor after debulking surgery and ER status were associated with OS (p< or =0.05). CONCLUSIONS: Ki67 nuclear expression >30% is predictive of complete response in advanced ovarian cancer. HER2/neu overexpression is scarce in our study. Positive ER is an independent prognostic factor for OS. Further research with larger studies and hormonal treatment is guaranteed.     

外源性p53基因增加卵巢癌细胞对顺铂的敏感性

 目的 探讨外源性ｐ５３基因转染对人卵巢癌细胞株的化疗敏感性的影响。方法用脂质体介导的转染技术，将人野生型ｐ５３基因的真核表达载体导入不表达ｐ５３的卵巢癌ＳＫＯＶ－３细胞中，经Ｇ４１８筛选，Ｎｏｒｔｈｅｒｎｂｌｏｔ及Ｗｅｓｔｅｒｎｂｌｏｔ鉴定后，观察其对顺铂作用后的 ＳＫＯＶ－３细胞的集落形成及凋亡的影响。结果 外源性Ｐ５３基因在转染细胞中有效表达，并增强了顺铂对ＳＫＯＶ－３细胞集落形成的抑制作用及促进了顺铂诱导的细胞凋亡。结论 外源性ｐ５３基因能增加卵巢癌细胞对顺铂的敏感性，两者联合作用能更大程度地杀灭肿瘤细胞。     

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抑癌基因、nm23肿瘤转移抑制基因 在卵巢上皮性癌的表达

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p53和nm23在卵巢癌中的表达及意义

目的 研究p53抑癌基因和nm23肿瘤转移抑制基因与卵巢上皮性癌的关系.方法采用免疫组化SP法检测12例正常卵巢组织,20例卵巢良性肿瘤,16例交界性肿瘤以及79例卵巢上皮性癌组织中p53及nm23的表达情况.结果 p53表达率于卵巢上皮性癌为48.1%,其他组织均呈阴性,与组织类型无关,但与分化程度成反比,与分期、淋巴结转移成正相关.COX模型单因素及多因素分析显示,p53表达与预后相关;nm23表达率于卵巢上皮性癌中为49.3%,且与组织类型、细胞分化,临床分期以及淋巴结转移均有相关性,COX模型单因素分析表明nm23表达与预后有关.结论 p53和nm23可作为估计患者预后的指标,前者阳性者预后欠佳,后者阳性者预后较好.     

Prognostic importance of DNA ploidy and p53 in early stages of epithelial ovarian carcinoma.

Patients with early stages (FIGO stages IA-IIC) of ovarian cancer continue to experience tumor relapses and they succumb due to their disease after seemingly adequate adjuvant therapy. In a series of 113 patients treated with adjuvant radiotherapy 4-6 weeks after primary surgery, the DNA content and p53 status of the tumors were studied and related to other known prognostic factors (age, FIGO stage, histopathologic type, and tumor grade). The DNA analyses were done by flow cytometry and p53 expression was studied by immunohistochemistry on formalin-fixed and paraffin-embedded tissue. DNA analyses of 103 tumors could be made and the p53 status was determined in 106 cases. Univariate analyses showed that both p53-positivity and aneuploidy of the ovarian tumors were strongly associated with tumor grade. There was also a strong association between p53 expression of the tumors and DNA aneuploidy (DNA index >1.10 and S-phase fraction >11.5%). P53-positivity and tumor grade were the only significant factors for the risk of tumor recurrence. DNA and p53 status alone were not adequate predictive factors to identify clinically relevant subgroups of patients who would benefit from adjuvant postoperative therapy. Tumor grade remains the most important prognostic factor with regard to the risk of tumor recurrence and the cancer-specific survival rate in early stage ovarian carcinoma. Overexpression of p53 also increases the risk of tumor recurrence.     

Prognostic value of P53 mutations in rectal carcinoma

The influence of p53 mutations on the response to ionizing radiation and survival was retrospectively evaluated in patients treated with preoperative radiotherapy for rectal carcinoma. From 1989 to 1991, 86 rectal cancer patients treated by preoperative radiotherapy were included in this series. For all patients, endorectal sonography (to define ultrasonography TNM [uTNM]) was performed before treatment; 19 patients were classified as stage 1, 27 as stage 2 and 40 as stage 3. Response to radiotherapy (39 Gy in 13 fractions delivered in 17 days) was assessed by comparing the uT and the T obtained by histologic examination of the resected specimen (TNM classification). A rectal cancer biopsy was performed before treatment and enabled the search for p53 mutations by denaturing gradient gel electrophoresis (DGGE) and sequencing. The status of the p53 gene was correlated with the response to radiotherapy and survival. Forty-nine percent of the tumors presented abnormal DGGE profiles. The prevalence of p53 mutations was significantly higher in patients who did not respond to radiotherapy (63%) than in those who did respond (34%) (p < 0.01). Presence of a p53 mutation was associated with significantly shorter 5-year survival compared to patients without mutations (p < 0.02). In a multivariate analysis, p53 mutation status remained a prognostic factor independent of tumor posttreatment staging (p < 0.05). p53 status is an independent prognostic factor of response to radiotherapy and survival in rectal carcinoma.     

Prognostic value of p53 for local failure in mastectomy-treated breast cancer patients.

PURPOSE: The loss of p53 function is a recognized adverse prognostic factor in invasive breast cancer. Several studies have shown a relationship between the nuclear accumulation of p53 protein (a surrogate marker of p53 inactivation) and poor disease-free and overall survival. In general, however, these studies did not report the prognostic value of p53 for local failure, which we have therefore assessed retrospectively here. MATERIALS AND METHODS: Accumulation of p53 protein was evaluated by immunohistochemistry in 1,530 mastectomy-treated breast cancer patients (259 radiation therapy [RT]- and 1,271 mastectomy only [No RT]-treated patients). Statistical comparisons were made between p53 protein accumulation, estrogen/progesterone receptors, nodal status, tumor size, and local failure rate (LFR). Local failure was defined as tumor recurrence involving the chest wall and/or the ipsilateral supraclavicular/axillary lymph nodes. The median follow-up period was 62 months. RESULTS: In the No RT group, the LFR was 9.1% and 16. 5% in p53-negative and p53-positive patients, respectively (P<.001). Multivariate analysis revealed that p53 protein accumulation was significantly associated with an increased risk of local relapse (relative risk [RR], 1.7; 95% confidence interval [CI], 1.2 to 2.4). Nodal status and tumor size were also significant factors. In the RT group, the LFR was 9.3% and 21.5% in p53-negative and p53-positive patients, respectively (P = .009). Multivariate analysis revealed that p53 protein accumulation was significantly associated with an increased risk of local relapse (RR, 2.5; 95% CI, 1.1 to 5.7), as was nodal status. CONCLUSION: Nuclear accumulation of p53 protein is independently associated with a significantly increased local failure rate in breast cancer patients treated with mastectomy, with or without radiation.