Prognostic significance of clinical parameters and biological markers in patients with squamous cell carcinoma of the head and neck treated with concurrent chemoradiotherapy.

Concurrent chemoradiotherapy is reported to have a fair clinical outcome with organ preservation for patients with squamous cell carcinoma of the head and neck (SCCHN). The aim of this study was to determine whether biological markers are related to proliferative activity or apoptosis of tumor cells and whether clinical factors are associated with a clinical outcome in SCCHN patients treated with concurrent chemoradiotherapy. Immunostaining with antibodies specific for p53, bcl-2, bax, and MIB-1 was performed to evaluate expression of these proteins in formalin-fixed, paraffin-embedded specimens of 111 SCCHN patients treated with concurrent chemoradiotherapy (carboplatin, 100 mg/m2, four to six times every week; total radiation therapy dose of 40-65 Gy over 4-6.5 weeks). Multivariate analysis indicated that nodal status was a significant indicator of overall survival (OS; P = 0.001) and locoregional control (LRC; P = 0.002). In a univariate analysis, patients with a low MIB-1-positive index (< 40%) had better OS than those with a high MIB-1-positive index (> or = 40%; P = 0.013), although the difference was not statistically significant in a multivariate analysis (P = 0.060). Patients with bcl-2-positive tumors had better LRC than those with bcl-2-negative tumors, based on a multivariate analysis (P = 0.017). No statistically significant association was found between p53 or bax expression and clinical outcome. These results indicate that nodal status is the major prognostic factor in SCCHN patients treated with concurrent chemoradiotherapy. In addition, our findings suggest that bcl-2 positivity is associated with better LRC and that the proliferative activity of tumor cells might be prognostic for OS.     

Prognostic indicators for neuroblastoma: Stage,grade, DNA ploidy,MIB-1-proliferation index,p53, HER-2/neu and EGFr–a survival study

Neuroblastoma, a tumor of the sympathetic nervous system, is one of the most common solid malignancies in infants and represents 7% of all cases of childhood cancer outside of the central nervous system. Thirty-five samples of neuroblastoma from 31 patients were obtained from Duke University Medical Center between 1979 and 1991 and studied to determine the relative prognostic value of a number of clinical, histologic, nuclear, and oncogenic features. The features studied were: stage, Shimada classification, DNA ploidy, MIB-1-proliferation index and status for HER-2/neu, p53 and epidermal growth factor receptor (EGFr). Only age (P = .03), HER-2/neu (P = .01), and p53 (P = .02) reached statistical significance as prognostic indicators. The median survival for patients with no HER-2/neu expression was 12 months; median survival for patients with no HER-2/neu expression was 138 months. Similary, the median survival for patients with p53 expression was 12 months; patients with no p53 expression had a median survival was 144 months. The combination of either HER-2/neu or p53 positivity was especially strong as a prognostic indicator (p = .002).     

Clinical relevance of p53 and bcl-2 protein over-expression in laryngeal squamous-cell carcinoma

We investigated immunohistochemically the clinical relevance of the over-expression of the apoptosis-regulating proteins p53 and bcl-2 in a homogeneous series of 149 laryngeal squamous-cell carcinomas. p53 was over-expressed in 75 cases and bcl-2 in 39 cases. p53 and bcl-2 co-expression was found in 21 cases. p53 and bcl-2 immunoreactivity was significantly associated with poor histological differentiation and lymph-node metastases. Moreover, a significant statistical correlation was found between bcl-2 expression, supraglottic tumor site and advanced disease stage. p53/bcl-2 co-expression was significantly associated with poor differentiation, tumor extension, the presence of lymph-node metastases and advanced clinical stage. Univariate analysis showed that a lower probability of survival was significantly associated with supraglottic site, tumor extension, advanced clinical stage and p53/bcl-2 co-expression, but not with p53 or bcl-2 considered separately. In multivariate analysis, only tumor extension and supraglottic site retained their prognostic value. Our data suggest that clinical staging remains the most reliable predictive indicator of survival in patients with laryngeal carcinoma. Int. J. Cancer (Pred. Oncol.) 79:263–268, 1998.© 1998 Wiley-Liss, Inc.     

Prognostic significance of p53, bax and bcl-2 gene expression in patients with laryngeal carcinoma.

AIM: This study was designed to examine the prognostic significance of the coexpression of three genes (bax, bcl-2 and p53) which play a critical role in the apoptotic mechanisms in patients with squamous cell laryngeal carcinoma. MATERIALS AND METHODS: The immunohistochemical expression of bcl-2, bax and p53 genes was retrospectively examined in 38 patients with squamous cell laryngeal carcinoma and in five controls (necrotomic tissue). Tissue specimens were obtained both during the diagnostic biopsy and at the time of surgery. Clinicopathological and survival data were correlated with the staining results. RESULTS: Bcl-2 protein expression (P=0.0472), stage (P=0.0087) and lymph-node involvement (P=0.0488) were found to be independent prognostic factors. Increased bcl-2 protein expression correlated with a better 5-year survival (P=0.0472). Patients who were bcl-2(-)/p53(-) (n=25) or bax(+)/bcl-2(-) (n=13) had a significantly worse overall survival (P=0.0305 and P=0.0482, respectively). Similarly, patients who were bax(+)/bcl-2(-)/p53(-) (n=11) also had a worse 5-year survival compared with the rest of the group (P=0.0088). Changes that were noticed in bax and p53 protein expression from the time of biopsy until the time of surgery did not correlate with a significant increase in the overall survival. CONCLUSIONS: The expression of bcl-2 gene appears to be an independent prognostic factor for patients with laryngeal carcinoma. The coexpression of the genes studied can be used to determine aggressive clinical phenotypes.     

喉鳞癌组织中Bcl—2和P53蛋白表达及意义

为了探讨ｂｃｌ－２，Ｐ５３在喉鳞癌组织中的表达情况，预后的意义，我们应用免疫组化ＬＳＡＢ法对５３例喉鳞状上皮细胞癌组织进行ｂｃｌ－２，Ｐ５３基因蛋白表达的测定。结果显示：（１）４７．１７％的喉癌中检出突变型Ｐ５３蛋白，在部分喉癌旁不典型增生上皮中可见Ｐ５３蛋白表达，癌旁组织细胞已发生Ｐ５３基因突变可能是术后复发的根源，突变型Ｐ５３蛋白过度表达是喉癌发生的早期事件。     

Prognosis of adenocarcinoma of the uterine cervix: p53 expression correlates with higher incidence of mortality

We investigated the significance of prognostic markers-estrogen receptor, progesterone receptor, p53, MIB-1 and bcl-2 - in adenocarcinoma of the uterine cervix. In 101 patients with primary cervical adenocarcinoma, treated from 1989 to 2000, we evaluated clinical parameters in relation to these prognostic markers. Mean age of patients was 45 years. Seventy eight percent of the patients were in FIGO stage I, 16% stage II, 7% stage III and IV. estrogen receptor, progesterone receptor, p53 and bcl-2 immunoreactivity was scored as 0 (up to 5% positive cells), 1+ (5-25% of cells positive), 2+ (26-50% of cells positive), 3+ (51-75% of cells positive) or 4+ (>76% of cells positive). MIB-1 was scored in 10 categories: 0-10, 11-20, 21-30, 31-40, 41-50, 51-60, 61-70, 71-80, 81-90, 91-100. The overall survival rate was 67%. Survival was not influenced by estrogen receptor, progesterone receptor, MIB-1, or bcl-2 strongly positive staining. Only p53 showed significant influence on survival, even when adjusted for stage or tumor grade. In conclusion, it does not seems useful to determine estrogen receptor, progesterone receptor, MIB-1 or bcl-2 in cervical adenocarcinomas as an indication of prognosis: survival is not influenced by presence or absence. However, if p53 staining is strongly positive survival is significantly worse than in tumors scored as negative or weak positive.     

p53 nuclear accumulation is associated with extramedullary progression of multiple myeloma

Progression of multiple myeloma (MM) from intramedullary to extramedullary sites heralds an aggressive phase of the disease but to the best of our knowledge, biologic factors have not been studied in paired biopsies from medullary and extramedullary sites. In this study, we immunostained paired bone marrow and extramedullary biopsies from 12 cases of MM for p53, CD56 and MIB-1 (proliferative index). In addition, 22 cases of extramedullary plasmacytoma (EMP) without bone marrow involvement were included as a control group. p53 nuclear accumulations were detected in myeloma cells derived from the extramedullary sites in 9 (75%) of the 12 cases, whereas only 1 of (8%) 12 bone marrow myeloma specimens expressed p53 (P = 0.003). p53 expression was also more prevalent in extramedullary sites of MM than EMP (75% vs. 18%, P = 0.003). There was no significant difference in CD56 expression between intramedullary and extramedullary MM (17% vs. 33%, P = 0.64), or between intramedullary MM and EMP (17% vs. 38%, P = 0.25). The MIB-1 proliferation index increased significantly as plasma cells migrated from the bone marrow microenvironment to extramedullary sites (P = 0.0001). Our data indicates that p53 nuclear expression but not CD56 expression, along with increased proliferation index is associated with disease progression from intramedullary to extramedullary sites in MM.     

Prognostic significance of mutations in the p53 gene,particularly in the zinc-binding domains,in lymph node- and steroid receptor positive breast cancer patients

The aim of our study was to evaluate if p53 mutations, especially those in the L2/L3 domains of the p53 gene, add prognostic information for node-positive and steroid receptor positive breast cancer patients. Two hundred and five tumour samples from a randomised clinical trial of 596 lymph node- and steroid receptor positive breast cancer patients were included. All patients had been randomly allocated to receive 20 mg of adjuvant tamoxifen (TAM) daily for 2 years or TAM plus one cycle of low-dose, short-term chemotherapy. For detection of p53 mutations we used in vitro amplification by polymerase chain reaction and consecutively performed temperature gradient gel electrophoresis (PCR-TGGE) and direct sequencing. We found p53 mutations in 42/205 (20%) cases: 16/42 (38%) p53 mutations occurred within the L2/L3 domains of the p53 gene, and 26/42 (62%) outside the L2/L3 domains. p53 mutation served as a statistically significant parameter in predicting disease-free survival in univariate (P=0.02) and multivariate (P=0.009) analysis. For overall survival, no significant differences were observed. Patients with tumours that had p53 mutations within the L2/L3 domains of the gene showed no significant difference to those with mutations outside the L2/L3 domains for disease-free survival. For overall survival, mutations in the L2/L3 domains showed a marginally significant difference (P=0.05) in multivariate analysis, but not in univariate analysis (P=0.13). We conclude that mutation in the L2/L3 domains of the p53 gene is not an independent prognostic indicator of disease outcome for patients suffering from breast cancer with lymph node metastases and positive steroid receptors.     

Prognostic Role of CDKN2A Deletion and p53 Expression and Association With MIPIb in Mantle Cell Lymphoma

IntroductionMantle cell lymphoma (MCL) is a rare type of lymphoma, which despite improvements in therapies in recent decades, remains an incurable disease. There is currently no reliable marker of chemoresistance available. In this study, we investigated the prognostic role of MIPIb and the association with biological markers including SOX11, p53 expression, Ki-67, and CDKN2A.Materials and MethodsThis retrospective study was focused on 23 patients with newly diagnosed classical MCL, treated at the University Hospital of Bari (Italy) between January 2006 and June 2019.ResultsWe identified a MIPIb value ≥ 5.4440 as a prognostic parameter that correlates with p53 expression and CDKN2A deletion. We also observed that patients with p53 overexpression had a significantly higher MIPIb (5.52 ± 0.53) which in 80% of patients had a value higher than 5.4440. On the other hand, CDKN2A deletion was found more frequently (75%) associated with MIPIb ≥5.4440. Only the CDKN2A deletion was associated with a higher proliferation index, with 66.7% of samples having Ki67 ≥30%. From the survival analysis we found that patients with p53 overexpression and CDKN2A deletion have a significantly worse prognosis with a median overall survival of 50 (P = .012) and 52 months (P = .018), respectively.Conclusionp53 expression and CDKN2A deletion represent a reliable pretreatment prognostic factor that identifies patients who do not benefit from currently used immunochemotherapy-based therapies and who are candidates for diversified treatments with the aim of improving prognosis. The MIPIb represents a prognostic index that correlates well with these biological alterations and can be used in clinical practice as their surrogate.     

Δ133p53 is an independent prognostic marker in p53 mutant advanced serous ovarian cancer

Background:

We aimed to evaluate the clinical relevance of p53 and p73 isoforms that modulate the function of p53.

Methods:

This prospective multicentre study included 154 patients with stage III and IV serous ovarian cancer. A functional yeast-based assay and subsequent sequencing were performed to analyse the p53 mutational status. Expression of p53 and p73 isoforms was determined using RT–qPCR.

Results:

Δ133p53 expression constituted an independent prognostic marker for recurrence-free (hazard ratio=0.571, P=0.016, 95% CI: 0.362–0.899) and overall survival (hazard ratio=0.365, P=0.004, 95% CI: 0.182–0.731) in patients with p53 mutant ovarian cancer (n=121). High Δ40p53 expression was associated with favourable tumour grading (P=0.037) and improved recurrence-free survival (33.4 vs 19.6 months, P=0.029), but not overall survival (43.1 vs 33.6 months, P=0.139), in patients with p53 wild-type cancer (n=33). Neither the p53 mutational status nor p73 isoform expression possessed prognostic significance in the examined ovarian cancer cases.

Conclusion:

Δ133p53 expression was associated with prognosis in the vast majority of ovarian cancer cases, that is, patients with p53 mutant advanced serous carcinomas. Thus, our findings underline the importance of considering the complex p53 regulatory network.     

MIB-1, p53, bcl-2, and WAF-1 expression in pelvic lymph nodes and primary tumors in early stage cervical carcinomas: correlation with clinical outcome

A complete series of 40 cervical carcinomas with pelvic lymph node metastases were analysed immunohistochemically for prognostic markers. The aims of this study were to examine whether the detection of MIB-1, p53, bcl-2, and WAF-1 could be used as a prognostic marker for tumor recurrence and survival rate. During the period of observation (mean 222, range 72-360 months) 22 (55%) recurrences were encountered and 20 patients died of the disease. There were 35 squamous cell carcinomas (87.5%), 2 adenosquamous carcinomas (5.0%), and 3 pure adenocarcinomas (7.5%). One tumor (2.5%) was well differentiated, 12 tumors (30%) were moderately differentiated, and 27 tumors (67.5%) were poorly differentiated. The primary tumor grade (P=0.037) and radicality of the surgical margins (P=0.021) were significant prognostic factors with regard to tumor recurrence. The site and number of lymph nodes with metastases had no prognostic value. P53, bcl-2, and WAF-1 were not predictive factors for recurrences or the cancer-specific survival rate. The concordant expression of WAF-1 in the primary tumor and in lymph node metastases was lower than for p53 and bcl-2. The proliferative activity (MIB-1) seemed to be lower in tumor cells metastasized to the pelvic lymph nodes than in cells of the primary tumor. Expression of MIB-1 in lymph nodes was predictive of disease-free survival in both univariate and multivariate proportional hazard Cox analyses.     

Prognostic significance of K-ras,p53, bcl-2, PCNA,CD34 in radically resected non-small cell lung cancers

The aim of this study was to investigate the prognostic significance of a panel of biological parameters in patients with radically resected non-small cell lung cancers (NSCLC). 269 cases with pathological stage I-IIIA NSCLC were retrospectively analysed. Immunohistochemistry was performed to detect protein expression of p53, bcl-2, proliferating cell nuclear antigen (PCNA) and CD34. Polymerase chain reaction (PCR)/direct nucleotide sequencing method was used to detect mutations in K-ras (codons 12, 13, 61, exons 1-2). The Kaplan-Meier estimates of survival were calculated for clinical and biological variables using the Cox model for multivariate analysis. Histological subtype and the pathologic tumour extension (pT) were the most powerful clinical-pathological prognostic factors for survival (P=0.030 and P=0.031, respectively), whereas among the biological parameters, p53 overexpression (P=0.032) and K-ras mutation (P=0.078) had a negative prognostic role, as demonstrated by multivariate analysis. Conversely, bcl-2, PCNA and CD34 expression were not correlated with survival. Statistically significant associations between p53 expression and the squamous cell carcinoma (SCC) subtype, bcl-2 expression and SCC subtype, K-ras mutation and p53 negative expression, p53 and bcl-2, bcl-2 and PCNA overexpression were observed. In conclusion, some biological characteristics such as the K-ras and p53 status may provide useful prognostic information in resected NSCLC patients, in addition to the classical clinico-pathological parameters. However, further studies are needed to clarify the value of adopting biological prognostic factor into clinical practice.     

Class III β-tubulin,but not ERCC1, is a strong predictive and prognostic marker in locally advanced head and neck squamous cell carcinoma

BackgroundRecent researches revealed that class III β-tubulin (TUBB3) is a prognostic marker in various tumors and role of TUBB3 in head and neck squamous cell carcinoma (HNSCC) is not defined yet. We analyzed the significance of TUBB3 expression along with p53 and ERCC1 in locally advanced HNSCC patients receiving cisplatin-based induction chemotherapy.Materials and methodsRetrospective review of medical records at Seoul National University Hospital between 1998 and 2007 was carried out. Immunohistochemical stain of TUBB3, p53, and ERCC1 was done in paraffin-embedded tumor tissue. We assessed response to treatment, progression-free survival (PFS), overall survival (OS), and cancer-specific survival (CSS).ResultsEighty-five patients with oropharyngeal, hypopharyngeal, and laryngeal cancers received induction chemotherapy with 5-fluorouracil (5-FU) and cisplatin (n = 55), or 5-FU, cisplatin, and docetaxel (Taxotere) (n = 30). Eighty-three received definitive treatment after induction chemotherapy, where 62 received radiotherapy and 21 received surgery. TUBB3-positive patients showed lower response rate than TUBB3-negative patients (69% versus 88%, P = 0.039). Shorter median PFS was observed in TUBB3-positive group (12 versus 47 months, P = 0.001). Shorter median OS was observed in TUBB-positive group not reaching statistical significance (30 versus 59 months, P = 0.072). TUBB3 status significantly influenced CSS (35 months versus not reached, P = 0.017). Positive p53 status was related to poorer OS and CSS. ERCC1 showed no influence on chemotherapy response, PFS, OS, and CSS.ConclusionTUBB3 is a predictive and prognostic marker along with well-known p53 in HNSCC patients receiving cisplatin-based induction chemotherapy. Clinical impact of ERCC1 is not evident in this setting.     

Prognostic value of p53 and MIB-1 in transitional cell carcinoma of the urinary bladder with regional lymph node involvement

BACKGROUND: The effect of p53 protein expression and MIB-1 proliferative activity on survival and chemotherapeutic response in patients with lymph node (LN)-positive transitional cell carcinoma (TCC) of the urinary bladder remains unclear. The objective of this study was to assess the ability of these markers to predict disease-associated outcomes and response to chemotherapy in a cohort of patients with LN-positive TCC. METHODS: The authors examined the expression of p53 and MIB-1 in the LN metastases from 139 patients who underwent cystectomy for TCC at their institution. P53 and MIB-1 nuclear staining were quantified using an image-analysis system. Cox proportional hazards regression models were used to test associations of these markers with death from TCC, distant metastases, and local recurrence for all patients and in the subset of patients who were treated with adjuvant chemotherapy. RESULTS: The median p53 and MIB-1 indices were 45.2% and 30.3%, respectively. The median follow-up was 4.5 years (range, 0.1-10 years). There were no statistically significant associations noted between the p53 and MIB-1 indices and the outcomes studied. When the analysis was limited to patients who were treated with adjuvant chemotherapy (n = 37 patients), the p53 index was found to have no prognostic value; however, there was a significant association between MIB-1 and distant metastases (P = 0.049). When disease-specific survival rates were stratified according to p53 index and chemotherapy, patients exhibited a response to chemotherapy regardless of p53 index. CONCLUSIONS: p53 and MIB-1 were not found to be associated significantly with disease-related outcomes in patients with LN-positive TCC. Adjuvant chemotherapy appeared to be effective regardless of p53 status. MIB-1 may prove useful in predicting response to chemotherapy.     

Overexpression of p53 is correlated with poor outcome in premenopausal women with breast cancer treated with tamoxifen after chemotherapy

The aim of this study was to evaluate the difference in outcomes based on p53 overexpression of patients with breast cancer who received adjuvant therapy following local treatment for invasive ductal carcinoma, not otherwise specified. We analyzed data from 4,683 patients with cancer enrolled in two institutions between 1997 and 2006. We analyzed the correlation between p53 overexpression and relapse, response to adjuvant therapy, breast cancer-specific survival (BCSS), and relapse-free survival (RFS) in patients with primary breast cancer. Overexpression of p53 was noted in 1,091 patients (23.3%). A significant correlation existed between p53 overexpression and poor prognostic factors, an increased frequency of regional recurrence, visceral metastasis, and worse BCSS and RFS. Based upon subgroup analyses, combined age (<35, 35–50, and >50 years) and adjuvant therapy (hormone therapy only, chemotherapy only, and hormone therapy following chemotherapy), the greatest reduction of survival based on p53 overexpression was noted in patients 35–50 years of age who received hormone therapy following chemotherapy (P < 0.05). Multivariate analysis showed that p53 overexpression is an independent prognostic factor in patients treated with hormone therapy and chemotherapy (relative risk for BCSS, 2.003; 95% CI, 1.105–3.631; P = 0.022). The p53-overexpressing patients with breast cancer between 35 and 50 years of age who received tamoxifen following chemotherapy had the greatest adverse effect on outcome. Overexpression of p53 is significantly associated with tamoxifen resistance in premenopausal women with breast cancer.     

A Two-Gene Prognostic Classifier for Early-Stage Lung Squamous Cell Carcinoma in Multiple Large-Scale and Geographically Diverse Cohorts

IntroductionThere are no validated molecular methods that prospectively identify patients with surgically resected lung squamous cell carcinoma (SCC) at high risk for recurrence. By focusing on the expression of genes with known functions in development of lung SCC and prognosis, we sought to develop a robust prognostic classifier of early-stage lung SCC.MethodsThe expression of 253 genes selected by literature search was evaluated in microarrays from 107 stage I/II tumors. Associations with survival were evaluated by Cox regression and Kaplan-Meier survival analyses in two independent cohorts of 121 and 91 patients with SCC, respectively. A classifier score based on multivariable Cox regression was derived and examined in six additional publicly available data sets of stage I/II lung SCC expression profiles (n = 358). The prognostic value of this classifier was evaluated in meta-analysis of patients with stage I/II (n = 479) and stage I (n = 326) lung SCC.ResultsDual specificity phosphatase 6 gene (DUSP6) and actinin alpha 4 gene (ACTN4) were associated with prognostic outcome in two independent patient cohorts. Their expression values were utilized to develop a classifier that identified patients with stage I/II lung SCC at high risk for recurrence (hazard ratio [HR] = 4.7, p = 0.018) or cancer-specific mortality (HR = 3.5, p = 0.016). This classifier also identified patients at high risk for recurrence (HR = 2.7, p = 0.008) or death (HR = 2.2, p = 0.001) in publicly available data sets of stage I/II and in meta-analysis of stage I patients.ConclusionsWe have established and validated a prognostic classifier to inform clinical management of patients with lung SCC after surgical resection.     

Prognostic effect of p53 expression in patients with completely resected colorectal cancer

The p53 protein is closely involved in the carcinogenesis of many kinds of cancers. Though the prognostic role of p53 expression for the survival of colorectal cancer (CRC) patients has been preliminarily identified, the prognostic effect of p53 expression in patients with completely resected CRC is still unclear. Therefore, a retrospective cohort study was performed to assess the prognostic role of p53 expression for overall survival in patients with completely resected CRC. A total of 153 patients (mean age 50.9 years) with completely resected CRC was finally included in the retrospective cohort study. Kaplan-Meier product-limit methods and log-rank test were used to estimate overall survival distribution and test the difference. In addition, multivariable analysis by Cox regression model was also used to test the prognostic role of p53 expression on overall survival by adjusting for other confounding factors. Of those 153 CRC patients, 62 (40.5 %) were positive for p53 protein expression in the tumor tissues. The log-rank test showed that there was an obvious difference in the overall survival between the p53-positive group and the p53-negative group (P?P?=?0.009). Therefore, p53 protein expression in the tumor tissue is an independent predictor of shorter overall survival in patients with completely resected CRC.     

Significance of p53, Bcl-2, and HER-2/<Emphasis Type="Italic">neu</Emphasis> protein expression in Omani Arab females with breast cancer

Recial disparity in the presentation of breast cancer and the outcome of its treatment is well established. However, the causes remain unexplained. The scarcity of reports about the prognostic significance of p53, bcl-2, and HER-2/neu in Arab females with breast cancer has been the impetus to this study. We evaluated the prognostic significance of altered expression of p53, bcl-2,HER-2/neu in Omani Arab females with non-metastatic breast cancer with correlation to other established prognostic factors. We have retrospectively analyzed the immunohistochemical expression of p53, HER-2/neu and bcl-2 in paraffin embedded blocks of 72 females diagnosed with invasive breast cancer between 1992 and 2002. The expression of the above proteins was correlated with other prognostic factors and univariate and multivariate analysis was carried out for all prognostic factors. Overexpression of p53 significantly correlated with younger age (<40), pre-menopausal status, poor differentiation with inverse correlation with bcl-2 expression. Expression of bcl-2 immunopostivity significantly correlated to low histological grade and positive estrogen and progesterone receptor status. On univariate and multivariate p53 overexpression and lack of bcl-2 immunostaining resulted in worse survival outcome, but notHer-2/neu overexpression. Expression patterns of p53 and bcl-2 are independent predictors of survival in Omani Arab population which may help to stratify these patients into different risk groups.     

myc/bcl-2及myc/p53共表达与弥漫大B细胞淋巴瘤预后的相关性研究

目的 探讨myc/bcl-2和myc/p53共表达与弥漫大B细胞淋巴瘤(DLBCL)预后的关系.方法 选择山西省肿瘤医院2010年1月至2014年10月有详尽随访记录的DLBCL 148例.运用免疫组织化学(IHC)技术检测石蜡样本myc、bcl-2、p53蛋白的表达.结果 148例DLBCL患者myc、bcl-2和p53阳性表达率分别为35.1%(52/148)、60.1%(89/148)和24.3%(36/148).myc/bcl-2共表达37例(25.0%),与Hans分型(χ2=4.749,P=0.029)、国际预后指数(IPI)评分(χ2=4.894,P=0.027)、骨髓侵犯(χ2=4.751,P=0.029)、疗效评价(χ2=9.140,P=0.003)有关;myc/p53共表达17例(11.5%),与Hans分型(χ2=5.349,P=0.021)、乳酸脱氢酶(LDH)水平(χ2=11.1,P=0.001)有关.单因素分析结果显示,myc[总生存期(OS):χ2=6.044,P=0.014;无进展生存期(PFS):χ2=6.212,P=0.013]、bcl-2(OS:χ2=5.812,P=0.016;PFS:χ2=4.878,P=0.027)、p53(OS:χ2=20.092,P<0.0001;PFS:χ2=18.492,P<0.0001)、myc/bcl-2共表达(OS:χ2=11.277,P=0.001;PFS:χ2=9.024,P=0.003)、myc/p53共表达(OS:χ2=21.150,P<0.0001;PFS:χ2=18.655,P<0.0001)均是影响预后的不良因素.此外,共表达组的生存率比单表达组的生存率更低,myc/p53共表达组生存率低于myc/bcl-2共表达组.多因素分析示,纳入myc、bcl-2、p53、myc/bcl-2、myc/p53及治疗方案6个独立变量,p53表达是影响患者OS(95%CI0.172~0.763,P=0.008)及PFS(95%CI 0.172~0.773,P=0.009)的独立不良预后因素.结论 myc、bcl-2、p53均为DLBCL的不良因素;myc/bcl-2、myc/p53共表达具有协同作用,提示预后更差.     

Identifying the survival subtypes of glioblastoma by quantitative volumetric analysis of MRI

This study was to project a powerful volumetric-related parameter on magnetic resonance imaging (MRI) for classifying patients with glioblastoma multiforme (GBM) into distinct subgroups objectively. The preoperative MRIs of 147 patients with primary GBM were analyzed. Volumetric-related parameters, including V1 (tumor volume), V2 (peritumoral T2/FLAIR hyperintense volume) and V2/V1 (the volume ratio), were estimated by an ellipsoid model. Log-rank analysis and Cox regression methods were used to compare Kaplan–Meier plots and identified prognostic parameters. Log-rank analysis revealed that V1 and V2 were correlated with survival, but the P value was marginally significant (P = 0.082, P = 0.091, for progression-free survival [PFS]; P = 0.120, P = 0.073, for overall survival [OS], respectively). V2/V1 was a potential prognostic factor for both PFS and OS (P < 0.001 and P < 0.001, respectively). Cox regression analysis documented that higher V2/V1 (ratio ≥ 7.0) was independent unfavorable prognostic factor. The odd ratio (OR) of higher V2/V1 was 2.662 (95 % confidence interval [CI], 1.782–3.975; P < 0.001) for PFS and 3.450 (95 % CI, 2.079–5.725; P < 0.001) for OS, respectively. The volumetric-related parameters of V1, V2 and V2/V1 were helpful for predicting the prognosis of patients with GBM. V2/V1 was a more comprehensive and systematic prognostic factor in GBM patient, especially for those with small tumor but large peritumoral T2 hyperintense or large tumor but small peritumoral T2 hyperintense.