Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In vitro studies suggest that p53 codon 72 genotype alters the apoptotic capacity of p53 protein, with the 72 arginine (R) form of wild-type p53 harboring a greater apoptosis-inducing potential than the 72 proline (P) variant. The aim of this study was to investigate whether the association between the p53 codon 72 genotype and breast cancer survival was modified by p53 gene status. In our study, we examined the p53 codon 72 genotype and p53 mutations (through exons 4-9) in paraffin-embedded specimens from 414 breast cancer patients with a median follow-up of 8.2 years. We report that the p53 codon 72 genotype was significantly associated with disease-free survival (DFS, p = 0.02) but not with disease-specific survival (DSS, p = 0.24) in the entire study population (n = 414). In contrast, the codon 72 genotype was strongly associated with both DFS (p = 0.001) and DSS (p = 0.04) among patients with a wild-type p53 tumor (n = 346), patients with the P/P variant had worse DFS and DSS than did those with the P/R or R/R variant in this subgroup of patients. More importantly, as compared with the P/R or R/R variant, the P/P variant remained an independent prognostic factor of DFS among patients with a wild-type p53 tumor (HR = 2.5; 95%CI = 1.4-4.4; p = 0.003). We conclude that the effect of p53 codon 72 genotype on breast cancer survival is dependent on p53 gene status, the P/P variant is strongly associated with poor prognosis among patients with a wild-type p53 tumor.
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PMID:Effect of p53 codon 72 genotype on breast cancer survival depends on p53 gene status. 1834 41

Low gene expression of folylpolyglutamate synthase (FPGS) in colorectal mucosa correlates with low folate levels and poor survival of colorectal cancer (CRC) patients. Because gene-specific hypermethylation is affected by the folate level, the hypermethylation status in mucosa may also be linked to clinical outcome of CRC patients. The tumor suppressor gene p16INK4a (p16) regulates the cell cycle and angiogenic switch. In human neoplastic tissues, the main mechanism of p16 inactivation is promoter methylation. The aim of the study was to determine whether hypermethylation of the p16 promoter could be detected in mucosa of CRC patients (n = 181) and to analyze if hypermethylation was related to survival. The relation between p16 hypermethylation and expression of FPGS and two other folate-associated genes, reduced folate carrier 1 (RFC-1), and thymidylate synthase (TS), was analyzed (n = 63). The results showed that p16 was hypermethylated in 65 (36%) of the mucosa samples and that hypermethylation was age-related (P = 0.029). After adjustment for known risk factors, Cox regression analysis showed that Dukes' A-C patients with p16 hypermethylation in mucosa had an increased risk of cancer-related death (hazard ratio = 2.9, P = 0.007) and shorter disease-free survival (hazard ratio = 2.5, P = 0.015) compared with patients with no p16 hypermethylation. RFC-1 and FPGS gene expression levels were significantly correlated in patients lacking p16 hypermethylation in mucosa (P = 0.0003), but not at all correlated in patients having hypermethylation in mucosa (P = 1.0). In conclusion, p16 hypermethylation in mucosa of CRC patients was identified as an independent prognostic parameter for cancer-specific survival as well as an independent predictor of DFS. The results suggest that there might be a connection between folate-associated gene expression and p16 methylation status.
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PMID:p16INK4a gene promoter hypermethylation in mucosa as a prognostic factor for patients with colorectal cancer. 1841 63

The purpose of our study was to analyze the indicators of loco-regional failure in a large cohort of patients with gingivobuccal complex tumors treated at a single institution. A retrospective review of 2275 patients diagnosed with tumors of the gingivobuccal complex was conducted from January 1997 to December 1999; 642 patients who fulfilled our inclusion criteria were analyzed. A univariate analysis, multivariate analysis, and disease-free survival are reported. During a median follow up of 2.51 years, there were 228 (35.5%) recurrences with a median post-recurrence survival of 2.7 months. The incidence of occult neck metastasis was 29%. The 2- and 5-year DFS rates were 63.8% and 53.3%, respectively. On multivariate analysis, tumor depth and metastatic lymphadenopathy were found to be independent prognostic factors for disease-free survival. Advanced gingivobuccal cancers fail loco-regionally. Cervical metastasis and tumor depth influence disease-free survival. Elective neck dissection due to a high incidence of occult neck disease is recommended.
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PMID:Squamous cell carcinoma of the gingivobuccal complex: predictors of locoregional failure in stage III-IV cancers. 1862 71

Invasive ductal carcinomas (IDC) of the breast with the triple negative phenotype (steroid hormone receptor absent, negative HER2 status) are characterized by poor clinical outcome. Additional tumor markers might allow identification of patients at higher risk. We evaluated clinical and biological features of 284 consecutive patients with pT1-3, pN1-3 M0 triple-negative IDC. Median follow-up was 70 months (interquartile range 59-94 months). Statistically significant worse disease-free and overall survival were observed in multivariate analysis, for patients with EGFR immunoreactivity in >or=50% invasive tumor cells (HR 2.39, 95% CI, 1.32-4.34, P = 0.004 for DFS; HR 2.34, 95% CI, 1.20-4.59 P = 0.01 for OS). Age >or= 70 years and PVI were additional independent predictors of reduced overall survival. EGFR immunoreactivity significantly correlates with worse prognosis in patients with triple-negative IDC, supporting further studies on the correlation between the degree of EGFR expression and outcome of triple negative breast cancer.
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PMID:Invasive ductal carcinoma of the breast with the "triple-negative" phenotype: prognostic implications of EGFR immunoreactivity. 1883 7

Colorectal cancer (CRC) cell lines displaying microsatellite instability (MSI) are resistant to 5-fluorouracil in vitro, which can be overcome by restoring DNA mismatch repair (MMR) competence. Furthermore, elevated levels of Bcl-2 protein confers cytotoxic drug resistance to tumour cell lines. We examined the expression of Bcl-2 and two MMR proteins (hMLH1 and hMSH2) in advanced CRC patients, to determine their mutual relationship, association to therapeutic response and impact on disease outcome. Tumour samples from 73 CRC patients who were treated in advanced stage with either irinotecan alone or in combination with 5-FU/leucovorin, were analysed for expression of Bcl-2, hMLH1 and hMSH2 using immunohistochemistry. Bcl-2 expression was closely correlated with hMLH1 and hMSH2 expression (negative-weak/moderate-strong) (p=0.01). Bcl-2/MMR expression was significantly (p=0.030 for whole series; p=0.018 for the 5-FU-treated cases) related to the response to treatment; tumours with low levels of both Bcl-2 and MMR responded better (n=18/31, 58%) than those with high Bcl-2 and MMR (n=3/16, 18%). Patients with high Bcl-2/MMR expression had a significantly longer DFS (47 vs. 11 months, n=26) than those with low Bcl-2/MMR index (p=0.005). Bcl-2/MMR index was not significantly related to disease-specific survival or survival with metastases. The present data suggest that MSI patients with low Bcl-2/MMR demonstrate a significantly shorter DFS, whereas patients with high expression of the two markers obtain the greatest benefit from 5-FU-based chemotherapy.
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PMID:Oncoprotein Bcl-2 and microsatellite instability are associated with disease-free survival and treatment response in colorectal cancer. 1894 93

The outcome of Ewing's sarcoma depends on the anatomical site of the tumor. Studies conducted in high-risk patients are limited. We evaluated the outcome of high-risk Ewing's sarcoma patients that received long-term treatment protocol. Twenty-five patients (22 males, 3 females) with poor prognostic features were treated according to long-term Ewing's sarcoma protocol. Central-axis localization, inadequacy or unavailability of surgical resection, older than 15 years of age, are accepted as high-risk factors. The median age of patients was 23 years (range, 18-55). The tumor localization was pelvis (9), femur (1), tibia (1), fibula (1), maxilla (1), clavicle (1), vertebrae (5), metatarse (1), and ribs (5). Neoadjuvant chemotherapy was applied between weeks 0 and 6, local therapy on week 9, and adjuvant maintenance chemotherapy between weeks 11 and 41. All patients received neoadjuvant and adjuvant maintenance chemotherapy. Local therapy consisted of radiotherapy (32%), surgery alone (12%), or surgery and radiotherapy (56%). The median total treatment period was 10 months. The median follow-up was 25 months (range, 7-89). Three-year cumulative OS and DFS rates were 43% (95% CI, 28.5-57.85) and 40% (95% CI 23.63-52.19), respectively. The most common grade III/IV toxicities observed during the treatment protocol were neutropenia (16%) and gastrointestinal toxicities (16%). Our study indicated that long-term multiagent combination chemotherapy may result in better outcome in adult high-risk patients undergoing adequate surgical resection of the tumor and local radiotherapy. Further randomized studies are needed to assess the efficacy of this treatment protocol in patients with adequate surgical margins.
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PMID:Long-lasting multiagent chemotherapy in adult high-risk Ewing's sarcoma of bone. 1898 98

Hepatocellular carcinoma (HCC) is an aggressive cancer with a poor prognosis. The role of autophagy and the prognostic value of autophagic genes are largely unknown in HCC. Here, we showed decreased expression of autophagic genes and their corresponding autophagic activity and increased expression of the antiapoptotic gene Bcl-xL in HCC cell lines compared with a normal hepatic cell line. We also found decreased expression of the autophagic gene Beclin 1 in 44 HCC tissue samples compared with adjacent nontumor tissues. In addition, we found that the most aggressive malignant HCC cell lines and HCC tissues with recurrent disease displayed much lower autophagic levels, especially when Bcl-xL was overexpressed. Interestingly, in a tissue microarray study consisting of 300 HCC patients who underwent curative resection, the expression of Beclin 1 was only significantly correlated with disease-free survival (DFS; P < 0.0001) and overall survival (OS; P < 0.0001) in the Bcl-xL(+) group. Multivariate and univariate analyses also revealed that Beclin 1 expression was an independent predictor for DFS and OS in Bcl-xL(+) patients. In addition, we found a significant correlation between Beclin 1 expression and tumor differentiation in Bcl-xL(+) but not in Bcl-xL(-) HCC patients. In conclusion, our data showed expression of autophagic genes and their corresponding autophagic activities were suppressed in HCC. The autophagy defects synergized with altered apoptotic activity might facilitate tumor malignant differentiation, which results in a more aggressive cancer cell phenotype and poor prognosis of HCC.
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PMID:Association of autophagy defect with a malignant phenotype and poor prognosis of hepatocellular carcinoma. 1901 Aug 88

To evaluate whether HER2 mRNA could be used as a marker of circulating tumor cells (CTCs) in women with operable breast cancer. A nested RT-PCR assay was developed and used for the detection of HER2 mRNA-positive CTCs. Blood from 216 women with early breast cancer obtained before adjuvant treatment was tested for HER2 mRNA-positive cells to assess their prognostic value. Nested RT-PCR for HER2 mRNA showed high sensitivity whereas no HER2 mRNA-positive cells could be identified in the blood of healthy donors. HER2 mRNA-positive CTCs were detected in 53 (24.5%) of 216 patients and HER2 mRNA detection was associated with reduced disease-free survival (DFS; P < 0.0001) and overall survival (OS; P = 0.004). In multivariate analysis, detection of HER2 mRNA-positive CTCs emerged as independent prognostic factor for DFS (P = 0.0001) and OS (P = 0.003). HER2 mRNA could be a valuable prognostic marker for the detection of CTCs in early breast cancer patients.
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PMID:Detection of occult HER2 mRNA-positive tumor cells in the peripheral blood of patients with operable breast cancer: evaluation of their prognostic relevance. 1911 5

Matrix-producing carcinoma (MPC) of the breast is a subtype of metaplastic carcinoma defined as an invasive breast carcinoma with a direct transition of carcinoma to cartilaginous or osseous matrix without an intervening spindle cell component. Our aims were (1) to evaluate specific histologic characteristics of MPC and correlate these with disease recurrence; and (2) to determine whether rates of locoregional and distant recurrence for MPC are significantly different from those of invasive ductal carcinoma. Thirty-two cases of MPC were identified. Fourteen patients (44%) were < or =50 years of age; 10 (31%) had tumors of size < or =2 cm, and 6 (19%) had tumors > or =5 cm. In this series, all tumors contained chondromyxoid or chondroid matrix, and 1 (3.1%) also contained focal (<5%) osseous matrix. High-grade matrix was present in 9 cases (28%), and low-grade matrix was present in 23 (72%). Matrix comprised < or =10% of the tumor in 14 cases (44%), >10% but <40% in 9 (28%), and > or =40% in 9 (28%). The carcinomatous component was high grade in 30 cases (94%), and 19 tumors (59%) had central necrosis. Seven patients (22%) had positive axillary lymph nodes, and 8 (25%) had lymphovascular space invasion (LVSI). LVSI was the only factor independently associated with locoregional recurrence-free survival in multivariate analysis (P=0.043). Although > or =40% matrix was associated with improved distant recurrence-free (DFS) survival in univariate analysis (P=0.044), only LVSI and tumor stage were independently associated with DFS survival in multivariate analysis (P=0.027 and P=0.001, respectively). Compared with matched controls with invasive ductal carcinoma, patients with MPC had decreased locoregional recurrence-free survival (P=0.001) and decreased DRF survival (P=0.001). In summary, MPC is an aggressive subtype of metaplastic carcinoma with a worse clinical outcome than invasive ductal carcinoma.
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PMID:Matrix-producing carcinoma of the breast: an aggressive subtype of metaplastic carcinoma. 1995 60

As with other solid tumor types, head and neck squamous cell carcinoma (HNSCC) has been identified as an epigenetic, as well as genetic, disease. Consequently, promoter hypermethylation, being the most important aberrant epigenetic characteristic, has been intensively investigated for its biomarker potential in this cancer type. As many of these evaluations are obscured by a heterogeneity of treatments, the current study aimed to evaluate the incidence and prognostic value of the promoter hypermethylation of TIMP3, CDH1, DAPK, RASSF1A, p16INK4A and MGMT in HNSCC treated solely by radiotherapy. In 46 patients with advanced HNSCC treated with a hybrid accelerated fractionation radiotherapy schedule, DNA extracted from pretreatment paraffin-embedded tumor biopsies was used to determine the methylation status of the genes of interest by methylation-specific PCR (MSP). The detected epigenetic silencing was related with outcome in terms of locoregional control (LRC), and overall (OS), disease-free (DFS) and disease-specific survival (DSS). Tumor biopsies revealed the epigenetic silencing of MGMT in 42.5% (17 of 40) of patients and of TIMP3 in 40.5% (17 of 42) of cases. For the remaining investigated genes, a lower methylation percentage was detected: 13.2% (5 of 38) for CDH1, 11.4% (4 of 44) for DAPK, 4.8% (2 of 42) for p16INK4A and 2.4% (1 of 41) for RASSF1A. The promoter hypermethylation of TIMP3 and CDH1 was significantly related with better LRC (p=0.009 and p=0.02, respectively), OS (p=0.005 and p=0.002, respectively), DFS (p=0.02 and p=0.004, respectively) and DSS (p=0.12 and p=0.007, respectively). In conclusion, in this representative group of 46 patients with advanced HNSCC treated by radiotherapy only, the epigenetic silencing of TIMP3 and CDH1 predicted a better outcome.
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PMID:Promoter methylation of TIMP3 and CDH1 predicts better outcome in head and neck squamous cell carcinoma treated by radiotherapy only. 1914 29


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