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At least 847 records · Page 47Linked to original sources
PubMed2003

Reduced bikunin gene expression as a factor of poor prognosis in ovarian carcinoma.

BACKGROUND: In previous studies, the authors showed that various types of cultured tumor cells treated with exogenous bikunin protein or ovarian carcinoma cells transfected with bikunin cDNA have low invasiveness and diminished metastatic potential. This study was carried out to clarify the relation between the expression of individual bikunin mRNA and tumor progression. METHODS: Forty-one newly diagnosed ovarian carcinomas were investigated using a semiquantitative reverse transcriptase-polymerase chain reaction. RESULTS: The authors found that 24 patients had tumors that overexpressed bikunin and that gene expression was reduced in the tumors of the remaining 17 individuals. Bikunin mRNA expression was independent of age, surgical stage, tumor size, degree of differentiation, histologic subtype, and serum CA 125 levels. There was a significant correlation between low expression of bikunin mRNA and lymph node status (P=0.035) or peritoneal status (P=0.042). Multivariate analysis indicated that bikunin was an independent prognostic marker (P=0.013; hazard ratio, 2.30; 95 % confidence interval, 1.13-4.19), even after controlling for lymph node metastasis and the degree of peritoneal dissemination. In addition, low expression was a significant predictor for poor prognosis compared with high expression (2-year survival rate; 75.0 % vs. 47.1 %, respectively; P<0.05). CONCLUSIONS: The data suggest that low bikunin mRNA expression by ovarian carcinoma cells may be associated with poor prognosis. It is conceivable that testing for bikunin mRNA may identify patients with ovarian carcinoma who are at high risk for early disease recurrence and a poor prognosis.

Adenocarcinoma↗
PubMed2003

Myoid differentiation and prognosis in adult pleomorphic sarcomas of the extremity: an analysis of 92 cases.

BACKGROUND: The results of a recent study demonstrated an association between myoid differentiation and an adverse prognosis in adult patients with pleomorphic sarcoma, as determined by 5-year metastasis-free survival rates. METHODS: To confirm the importance of muscle differentiation on prognosis in a well controlled clinical context, 92 samples from patients with pleomorphic sarcoma of the extremity from a single institution were immunostained with 4 monoclonal antibodies believed to be correlated with myoid differentiation: alpha-smooth muscle actin, muscle-specific actin, desmin, and myoglobin. RESULTS: Forty-two cases were positive for at least 1 muscle marker and 50 cases were uniformly negative. Between the two groups, there was no significant difference in tumor size, tumor extent, or patient age found; however, histologic grade was significantly higher (P = 0.038) in the myoid tumors. The 5-year survival differed significantly between patients with myoid tumors (35%) and those without myoid tumors (65%) (P = 0.0054). Myoid differentiation remained an adverse prognostic indicator after adjusting for clinically significant factors (i.e., histologic grade, tumor size, tumor extent, and patient age) (P = 0.01) (hazard ratio, 2.39; 95% confidence interval, 1.24-4.63). Furthermore, there was an inverse relation found between the number of myoid markers present and survival (P = 0.004). CONCLUSIONS: Myoid differentiation was found to be an independent indicator of adverse prognosis in adult patients with pleomorphic spindle cell sarcoma of the extremity.

Actins↗
PubMed2004

Follicular thyroid carcinoma: histology and prognosis.

BACKGROUND: Follicular thyroid carcinoma (FTC) is the second most common thyroid malignancy after papillary thyroid carcinoma. The authors studied the clinical course of 132 patients with FTC to determine whether there was a direct relation between the histologic degree of invasion, tumor recurrence, and patient survival. METHODS: The 132 patients in the study population underwent 182 thyroid carcinoma-related operations, and their mean follow-up was 7.5 years (median:,6 years; range, 0-39 years). The following criteria were used to define malignant follicular neoplasms: 1) minimally invasive, tumor invasion through the entire thickness of the tumor capsule; 2) moderately invasive, tumor with angioinvasion (with or without capsular invasion); and 3) widely invasive, broad area or areas of transcapsular invasion of thyroid and extrathyroidal tissue. Forty-five of 119 patients (37.8%) presented with minimally invasive FTC (capsular invasion only), 50 patients (42%) presented with moderately invasive FTC (angioinvasion with or without capsular invasion), and 24 patients (20%) presented with widely invasive FTC. At presentation, 12 patients (9%) had distant metastases, and 8 patients (6%) had lymph node metastases. RESULTS: Excluding 12 patients who presented with distant metastases, 21 patients (16%) developed recurrent metastases 6 months after their initial treatment. Among 45 patients with capsular invasion only, 6 patients (13%) developed recurrent or persistent disease, and 5 patients (11%) died. Of the 50 patients who had angioinvasion with or without capsular invasion, 10 patients (20%) developed recurrent or persistent disease, and 7 patients (14%) died. Patients who had angioinvasion with or without capsular invasion had a less favorable prognosis compared with patients who had capsular invasion only (P < 0.0001). Among patients who had widely invasive FTC, 9 of 24 patients (38%) developed recurrent disease, and 8 patients (33%) died; in addition, 7 of the other 24 patients (29%) had persistent disease and died. The overall death rate for patients with widely invasive FTC was 62%. Patients with persistent disease had a poorer prognosis compared with patients who had recurrent disease (P < 0.0001). Twenty-eight patients (21%) in the entire group died of FTC. CONCLUSIONS: In the current retrospective investigation, the authors demonstrate that patients with minimally invasive FTC (capsular invasion only) had a slightly better survival rate at 5 years (98%) compared with patients who had angioinvasion with or without capsular invasion (80%) and had better survival compared with patients who had widely invasive FTC (38%). Other (but not all) reports in the literature support the findings that FTC with angioinvasion is more aggressive than FTC with only capsular invasion yet is less aggressive than widely invasive FTC. The authors conclude that FTC no longer should be classified as either minimally invasive or widely invasive; rather, they recommend classifying FTC as minimally invasive, moderately invasive, or widely invasive, because prognosis varies according to these groupings.

Adenocarcinoma, Follicular↗
PubMed2004

Breast carcinoma diagnosis, treatment, and prognosis before and after the introduction of mass mammographic screening.

BACKGROUND: The introduction of breast carcinoma screening leads to early detection and is believed to reduce mortality and increase the proportion of patients for whom breast-conserving surgery is possible. METHODS: In 1992, a population-based mammographic screening program was introduced in the Dutch city of Tilburg and its surroundings; the program achieved total coverage in 1996. The authors examined the effects of this screening program by investigating disease stage, treatment, and survival among women diagnosed with breast carcinoma at a teaching hospital in Tilburg during the periods 1985-1991 and 1992-1999. RESULTS: Between January 1, 1985, and December 31, 1999, 1400 patients were diagnosed with breast carcinoma. Among patients ages 50-69 years, the proportion of TNM Stage I breast carcinoma increased from 24% in 1985-1991 to 45% in 1992-1999 (P<0.001). The proportion of patients age <50 years with invasive breast carcinoma who underwent breast-conserving surgery decreased from 45% to 33% (P=0.011). Among patients ages 50-69 years, the overall survival rate during the period from 1992 to 1999 was significantly greater than the corresponding rate during the period from 1985 to 1991 (P=0.0009). Even after adjustments were made for tumor stage and patient age, a slight reduction in mortality risk was observed in this age group. No difference in stage distribution or prognosis was found among patients age <50 years or among patients age > or =70 years. Of the 168 invasive malignancies found in patients ages 50-69 years between 1997 and 1999, 68 (40%) were detected by the screening program, 47 (28%) were interval malignancies, and 53 (32%) were detected in nonparticipants or in women who did not participate in 1 or more screening rounds. Patients with screen-detected tumors had a much more favorable prognosis than did patients with interval malignancies (P=0.0018) or patients with clinically detected breast carcinoma (P<0.0001). CONCLUSIONS: Between 1992 and 1999, after the introduction of breast carcinoma screening, improved prognosis and more favorable tumor stage were observed among patients ages 50-69 years. Even after the screening program was fully implemented in 1996, the majority of invasive malignancies still were detected between screening rounds or in patients who did not participate in the program.

Adult↗
PubMed2004

alpha1-acid glycoprotein fucosylation as a marker of carcinoma progression and prognosis.

BACKGROUND: Serum alpha1-acid glycoprotein (AGP), an acute-phase protein secreted by the liver, carries alpha(1,3)-fucosylated structures on its 5 highly branched, N-linked sugar chains. METHODS: Serum AGP levels in patients with various types of malignancies (n=214 patients) were measured using an enzyme-linked immunosorbent assay with anti-AGP antibody. To investigate glycoforms that differed in their degree of branching and extent of fucosylation, serum AGP samples were analyzed by crossed affinoimmunoelectrophoresis (CAIE) with concanavalin A, and Aleuria aurantia lectin (AAL), and anti-AGP antibody. RESULTS: A significant difference (P <0.001) in serum AGP levels was observed in preoperative patients compared with levels in the healthy control group, but the levels in individual patients did not reflect their clinical status. Conversely, it was found not only that the patterns of AGP glycoforms differed widely in the patient group compared with the healthy control group, but they also changed depending on each patient's clinical status. Furthermore, AGP glycoforms seemed to be appropriate markers of disease progression and prognosis according to follow-up studies of 45 patients during prolonged preoperative and postoperative periods. CONCLUSIONS: Patients with advanced malignancies who had AGP glycoforms that contained highly fucosylated triantennary and tetraantennary sugar chains for long periods after surgery were likely to have a poor prognosis. However, patients who had AGP glycoforms without such changes were expected to have a good prognosis.

Biomarkers, Tumor↗
PubMed2005

Overexpression of macrophage migration inhibitory factor induces angiogenesis and deteriorates prognosis after radical resection for hepatocellular carcinoma.

BACKGROUND: Macrophage migration inhibitory factor (MIF) is a pivotal cytokine that regulates inflammatory and immune responses. Recently, many investigators reported that MIF is expressed highly in several tumors, including hepatocellular carcinoma (HCC). However, the role of MIF in tumor angiogenesis and patient prognosis has not been examined in patients with HCC. METHODS: The authors evaluated MIF expression in 56 samples of HCC by Western blot analysis, and the results were correlated with clinicopathologic factors and patient prognosis. MIF localization was determined by immunohistochemical methods, and the results were compared with tumor microvessel density (MVD), as assessed by anti-CD34 antibody. Furthermore, to validate the role of MIF in angiogenesis, both MIF expression during culture of HCC cells (using the Hep3B, HepG2, and Huh7 cell lines) under hypoxic condition and the angiogenic potential of recombinant MIF in an in vitro angiogenic model were examined. RESULTS: Tumors with high MIF expression had high alpha-fetoprotein levels (P = 0.049) and frequent intrahepatic recurrence (P = 0.043). Immunohistochemical MIF scores had a significant correlation with MVD (P = 0.007). Patients who had tumors with high MIF expression levels had a significantly worse (P = 0.025) disease-free survival, and this finding remained significant as an independent prognostic factor in the multivariate analysis. Hep3B cells had high expression of MIF at 6 hours and 12 hours after hypoxic stress and exogenous MIF stimulated endothelial tube formation in in vitro angiogenesis. CONCLUSIONS: The current findings suggest that MIF expression may play a pivotal role in the dismal prognosis of patients with HCC that may be attributable to the modulation of angiogenesis.

Aged↗
PubMed2005

Noninvasive assessment of tumor vascularity by contrast-enhanced ultrasonography and the prognosis of patients with nonresectable pancreatic carcinoma.

BACKGROUND: Studies have shown that angiogenesis is one of the factors that influences the prognosis of patients with solid tumors, including pancreatic carcinomas. However, none have assessed noninvasively the relation between angiogenesis and prognosis in patients with pancreatic carcinoma. Contrast-enhanced ultrasonography (US) not only is a convenient, harmless, and noninvasive imaging modality, but it also provides detailed information on tumor vascularity. The objectives of this study were to assess the vascularity of pancreatic carcinoma noninvasively by contrast-enhanced US and to clarify the prognostic value of tumor vascularity in patients with nonresectable pancreatic carcinoma. METHODS: Thirty-five consecutive patients with pathologically confirmed, nonresectable pancreatic carcinoma were examined with contrast-enhanced US before systemic chemotherapy. The correlations among tumor vascularity, clinicopathologic factors, and clinical outcomes then were analyzed statistically to investigate prognostic indicators. RESULTS: The median time to progression (TTP) was longer in patients who had avascular tumors compared with patients who had vascular tumors (110 days vs. 28 days, respectively; P=0.0072; log-rank test). The median survival also was longer in patients who had avascular tumors (267 days vs. 115 days, respectively; P=0.0034; log-rank test). A multivariate analysis using a Cox proportional hazards model revealed that tumor vascularity was a significant, independent factor that influenced TTP (P <0.001) and survival (P=0.022) along with primary tumor size and serum lactate dehydrogenase (LDH) level, which are well known as prognostic factors in patients with pancreatic carcinoma. CONCLUSIONS: The current results indicated that contrast-enhanced US may be useful in assessing the prognosis of patients with nonresectable pancreatic carcinoma who receive systemic chemotherapy.

Adult↗
PubMed2006

Central nervous system recurrence in adult patients with acute lymphoblastic leukemia: frequency and prognosis in 467 patients without cranial irradiation for prophylaxis.

Recurrence of acute lymphoblastic leukemia (ALL) in the central nervous system (CNS) confers a poor prognosis, although to the authors' knowledge, only a few studies have analyzed this issue in adults. For the current study, the authors analyzed the frequency, predictive factors, and prognosis of CNS involvement and recurrence in adult patients with ALL who did not receive cranial irradiation for CNS prophylaxis. Four hundred sixty-seven adult patients (age > or = 15 years) with ALL were treated on 4 protocols: ALL-89 (standard-risk and high-risk ALL; n = 108 patients), ALL-93 (high-risk ALL; n = 222 patients), ALL-96 (standard-risk ALL; n = 84 patients), and ALL3-97 (Burkitt leukemia; n = 53 patients). CNS prophylaxis consisted of intrathecal methotrexate, cytarabine, and hydrocortisone together with high-dose systemic methotrexate and cytarabine. The mean age (+/- standard deviation) was 33 years (+/- 16 years), and 272 patients were males. ALL subtypes included an early pre-B phenotype (15%), a common phenotype (45%), a pre-B phenotype (5%), a mature B phenotype (11%), and a T phenotype (24%). CNS involvement at diagnosis was observed in 18 patients (3.9%). Of 159 recurrences, 22 occurred (5.8%) in the CNS (14 isolated and 8 combined). A lactate dehydrogenase level > 1000 U/L was the only factor associated with the risk of CNS recurrence. A complete remission was attained in 7 of 22 patients (32%). The median overall survival after recurrence was 0.7 years for patients with isolated CNS recurrence, 0.13 years for patients with combined recurrence, and 0.41 years for patients with bone marrow recurrence (P = .11). The only 2 survivors underwent stem cell transplantation. The frequency of CNS recurrence in adult patients with ALL who do not receive radiotherapy for CNS prophylaxis was similar to the frequency observed in protocols that included cranial irradiation. A lactate dehydrogenase value >1000 U/L was the only factor found to be associated with CNS recurrence. The prognosis for patients who develop CNS recurrence is poor, identical to that for patients who develop bone marrow recurrence.

Adolescent↗
PubMed2006

Prognosis of late life depression: a three-year cohort study of outcome and potential predictors.

BACKGROUND: Late-onset depression (LOD) has a poor prognosis which may be worsened by the presence of cerebrovascular disease. Few studies have explored prospectively the influence of vascular risk factors on longer term prognosis. METHODS: The original study involved 50 patients with LOD and 35 healthy age matched controls. Follow-up was at three years. Baseline measures included clinical, neuroradiological and neuropsychological variables. Outcome was assessed by mortality, progression to dementia and clinical course of depressive disorder. RESULTS: Sixty-two (73%) of the original cohort agreed to be re-interviewed. Seven participants had died (all from the depressed group) and six developed dementia, all but one from the depressed group. Vascular dementia predominated (although not significantly so) among those with dementia at follow-up. For 28 depressed patients with complete follow-up data (56% of the original sample), poor outcome was predicted by lower High Density Lipoprotein (HDL), raised Erythrocyte Sedimentation Rate (ESR) and a higher score on the Hachinski Index scale and one test of immediate memory. Initial response to treatment was not associated with later outcome. CONCLUSION: Late-onset depressive disorder is associated with a high rate of mortality and possibly dementia. Biochemical and inflammatory markers may be important in prognosis and their role should be confirmed in future studies.

Age of Onset↗
PubMed2006

Prognosis as a determinant of free flap utilization for reconstruction of the lateral mandibular defect.

BACKGROUND: The purpose of this study was to determine whether patients with a poor prognosis for survival were more likely to undergo reconstruction with a pectoralis flap versus a free flap and whether the use of a pectoralis flap offered any perioperative advantage, such as a reduction in medical complications. METHODS: Fifty-five consecutive patients who underwent immediate reconstruction after a lateral mandibulectomy were retrospectively reviewed. RESULTS: Age >or=70 years (p = .03), moderate or severe comorbidity (p = .02), and involvement of the base of tongue by tumor (p = .04) were significantly associated with decreased utilization of a free flap (n = 36). Comorbidity was the main determinant of medical complications (p = .001) and length of hospital stay (p = .03). CONCLUSIONS: Expectations of prognosis bias the surgeon's decision regarding flap selection. Reconstruction with a pectoralis flap does not necessarily contribute toward the desired outcome of reduced medical complications. Any functional comparison between reconstructive groups needs to account for those differences in health status and prognosis that might explain any observed postoperative differences.

Age Factors↗
PubMedDate not supplied

Prognosis of primary hepatocellular carcinoma.

Prognosis of 600 consecutive patients with hepatocellular carcinoma was analyzed in relation to treatment. They were divided into three stages based on four parameters of advanced disease: ascites, tumor greater than 50% of the two-dimensional size of the liver, serum albumin below 3 gm per dl, and serum bilirubin above 3 mg per dl. Stage I had none of these signs; Stage II one or two signs, and Stage III three or all signs. Of 600 patients, 98 had resection, 333 had nonsurgical treatment (158 treated by intraarterial chemotherapy, 94 systemic chemotherapy, 77 transcatheter embolization, and 4 others) and 169 no treatment. The median survival of untreated patients was only 1.6 months from diagnosis, and no untreated Stage III patient lived more than 3 months; there was a median survival of 0.7 month. Surgically treated patients lived significantly longer than nonsurgical patients of comparable stages; median survival was 19.6 months in the former and 2.8 months in the latter. Whereas Stage I patients did fairly well without treatment, chemotherapy significantly prolonged survival of patients of Stages II and III. These results suggest that early diagnosis and hepatic resection improve prognosis in patients with hepatocellular carcinoma in the areas where this cancer frequently emerges unicentrically. In view of the generally poor prognosis, liver transplantation is recommended when resection is not possible or indicated, and before extrahepatic metastasis occurs.

Adolescent↗
PubMedDate not supplied

The value of the immunological subtypes and individual markers compared to classical parameters in the prognosis of acute lymphoblastic leukemia.

The value of the immunophenotypical subtypes and individual markers was compared with classical parameters in the prognosis of 150 patients with acute lymphoblastic leukemia (ALL). Regarding the immunophenotype, common-ALL had a better prognosis than T-ALL in the children's group. However, in adults the situation was different since both null and T-ALL patients had longer survival rates than the common pre-B group. Moreover, several individual markers add interesting prognostic information, either in ALL as a whole group or within the different immunophenotypes. Thus, the expression of CD10 and TdT had a significantly favourable influence in the outcome of the whole series of patients; within the T-ALL, those cases positive for CD10 also had a longer median survival (33 versus 17 months). In addition, in the common ALL patients group the expression of a relatively mature B marker--CD20--appeared to have a favourable prognosis (27 versus 13 months). Other non lineage specific markers, such as CD9 and CD38 did not seem to influence survival. Regarding the more conventional parameters, our data suggest that the classical age prognostic classification in children (less than 15 years) and adults can be improved using two cut-off points at 11 and 35 years. Moreover, the multivariate analysis showed that this variable, together with FAB morphology and WBC counts were the best combination of parameters for predicting survival. The present study shows that although the immunophenotype helps us in understanding the biological heterogeneity of ALL, having also prognostic implications, there are other clinical and hematological features that yield stronger prognostic information.

Adolescent↗
PubMed2007

The role of MDR-related proteins in the prognosis of adult acute myeloid leukaemia (AML) with normal karyotype.

Cytogenetic abnormalities are among the most important factors affecting the outcome of patients with acute myeloid leukaemia (AML), but approximately 40-50% of AML cases display a normal karyotype at diagnosis. Multidrug resistance (MDR) proteins overexpression is associated with worse prognosis in acute leukaemias, but its role in normal karyotype AML is less defined. We analysed the expression of P-glycoprotein (PGP), MDR-related protein (MRP) and lung resistance protein (LRP) in 135 adult patients with normal karyotype AML and its correlation with other biological features of the disease, to evaluate the impact of MDR proteins on response to therapy and on survival. Increased PGP expression was associated with lower rate of complete remission (CR; p = 0.006), similarly to advanced age. Cases overexpressing PGP displayed also a shorter event-free survival (EFS; 4 vs. 10 months, p = 0.035) and the increased expression of at least one MDR protein was associated with a reduced overall survival (OS; p = 0.038). Also age was predictive of worse prognosis. Our data confirm the prognostic role of MDR proteins, in particular of PGP, also in AML patients with normal karyotype at diagnosis. This finding could be used to stratify patients with different prognosis and to design risk-adapted therapeutic strategies.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2007

Changes in clinical characteristics, course, and prognosis of inflammatory bowel disease during the last 5 decades: a population-based study from Copenhagen, Denmark.

BACKGROUND: It remains uncertain whether the increasing incidence of inflammatory bowel disease (IBD) during the last decades has been accompanied by an alteration in the presentation, course, and prognosis of the disease. To answer this question, 3 consecutive population-based IBD cohorts from Copenhagen, Denmark (1962-2005), were assessed and evaluated. METHODS: Phenotype, initial disease course, use of medications, cumulative surgery rate, standardized incidence ratio of colorectal cancer (CRC), and standardized mortality ratio (SMR) were compared in the 3 cohorts, which had a total of 641 patients with Crohn's disease (CD) and 1575 patients with ulcerative colitis (UC). RESULTS: From 1962 to 2005, the proportion of IBD patients suffering from CD increased (P < 0.001), time from onset of symptoms to diagnosis of CD decreased (P = 0.001), and median age at diagnosis of UC increased (P < 0.01). The prevalence of upper gastrointestinal involvement and pure colonic CD varied significantly between cohorts. UC patients diagnosed in the 1990s had a higher prevalence of proctitis, received more medications, and had a milder initial disease course than did previous patients. The surgery rate decreased significantly in CD but not in UC. The risk of CRC in IBD was close to expected over the entire period, whereas the mortality of patients with CD increased (overall SMR, 1.31; 95% CI, 1.07-1.60). CONCLUSIONS: Despite variations in the presentation and initial course of IBD during the last 5 decades, its long-term prognosis remained fairly stable. Treatment of IBD changed recently, and future studies should address the effect of these changes on long-term prognosis.

Adolescent↗
PubMed2002

Recent thymic emigrants and prognosis in T- and B-cell childhood hematopoietic malignancies.

The concentration of T-cell receptor rearrangement excision DNA circles (TRECs) in peripheral blood mononuclear cells (PBMCs) is currently known to be a marker of recent thymic emigrants. We evaluated the hypothesis that TREC values would be lower in childhood T-cell hematopoietic malignancies than in childhood B-cell acute lymphoblastic leukemia (ALL) or healthy controls because the former category may reflect compromised thymic function. From the Greek national childhood leukemia/lymphoma database we obtained all 30 available T-cell leukemia/non-Hodgkin's lymphoma cases, 30 age- and sex-matched childhood B-cell origin cases of ALL and 60 healthy hospital controls. We compared TREC levels in PBMCs using a real-time PCR assay. There was highly significant reduction of TREC values in children with T-cell malignancies (median 3,100 TRECs/10(6) PBMCs), whereas children with B-cell origin ALL had slightly but nonsignificantly lower TREC values compared to healthy children (medians 19,300 and 22,500 TRECs/10(6) PBMCs, respectively). During a median follow-up period of about 19 months, only 4 children died. All of them had a T-cell hematopoietic malignancy and relatively low TREC values. The number of TRECs was higher among healthy girls than among healthy boys, and a similar pattern was evident in T-cell malignancies. It appears that there is a pattern of concordance of high TREC values with better disease prognosis in hematologic childhood malignancies. This applies to specific disease entities with better prognosis (B-cell origin ALL having higher TREC values than T-cell leukemia/lymphoma) and to gender, another important predictor of prognosis conditional on disease entity (girls having higher TREC values than boys); however, it may also be true for the survival of individual patients. These preliminary findings can be used as hypothesis-generating indications that should be confirmed in larger data sets.

Age of Onset↗
PubMed2003

Multigene analysis of Rb pathway and apoptosis control in esophageal squamous cell carcinoma identifies patients with good prognosis.

Deregulation of cell-cycle G(1)-restriction point control by disruption of Rb-pathway components is a frequent event in cancer. In concert with the inactivation of cell death pathways, such events not only contribute to tumor development but also determine the intrinsic and acquired resistance to cancer therapy and, ultimately, disease prognosis. We previously observed that the cyclin-dependent kinase inhibitor p16(INK4a) and the proapoptotic Bcl-2 homolog Bax are positive prognostic factors and identify patients with good prognosis in esophageal squamous cell carcinoma (SCC). In the present study, we therefore extend our analysis to additional genes controlling the G(1) restriction point and apoptosis, respectively. This retrospective analysis was performed in a cohort of 53 patients undergoing surgery for esophageal SCC with curative intent, i.e., R0 resection. Protein expression profiles of cyclin D1, p16(INK4a), Rb, p21(CIP/WAF-1), p53, Bax and Bcl-2 were analyzed by immunohistochemistry and compared to p53 mutational status, as determined by SSCP-PCR of exons 5-8. Loss of p16(INK4a), Rb, p21(CIP/WAF-1) or Bax and overexpression of cyclin D1 were associated individually with shorter overall survival, while Bcl-2 expression and p53 mutation were not of prognostic relevance. The longest survival was observed in a subgroup of patients whose tumors bore a combination of favorite genotypes, i.e., low cyclin D1 and high Rb, p21(CIP/WAF-1), p16(INK4a) and Bax protein expression. These results show that multigene analyses based on limited sets of functionally linked genes reliably identify patients with good vs. poor prognosis.

Adult↗
PubMed2005

Lower levels of nuclear beta-catenin predict for a poorer prognosis in localized prostate cancer.

Beta-catenin in its role as a nuclear signaling molecule has been implicated in prostate carcinogenesis primarily through modulation of androgen receptor activity. We defined the pattern of beta-catenin protein expression in the nuclei of normal, hyperplastic and malignant human prostate tissue and determined whether differences in expression were associated with disease progression and prognosis. Five normal prostates, 26 benign prostatic hypertrophy specimens, 232 radical prostatectomy specimens from patients with clinically localized prostate cancer (PC) and 20 cases of advanced PC were assessed for beta-catenin expression using immunohistochemistry. Nuclear beta-catenin expression in localized PC was significantly lower than that in benign prostate tissue (p < 0.001) and significantly higher than that in advanced PC tissue (p < 0.001). In addition, lower levels of nuclear beta-catenin expression (< 10% of cancer cells) predicted for a shorter biochemical relapse-free survival in patients with localized PC (p = 0.008) and were inversely correlated with preoperative prostate-specific antigen (PSA) levels (p = 0.01). Analysis of the low-risk subgroup of patients with preoperative PSA levels < 10 ng/ml demonstrated that lower levels of nuclear beta-catenin expression (< 10% of cancer cells) again predicted for a poorer prognosis (p = 0.006). In conclusion, lower levels of nuclear beta-catenin expression are found in malignant compared to benign prostate tissue. In addition, lower nuclear beta-catenin expression is associated with a poorer prognosis in localized PC, in particular, in the low-risk subgroup of patients with preoperative PSA levels < 10 ng/ml. Thus, the level of nuclear beta-catenin expression may be of clinical utility as a preoperative prognostic marker in low-risk localized PC.

Adolescent↗
PubMed2006

Akt is frequently activated in HER2/neu-positive breast cancers and associated with poor prognosis among hormone-treated patients.

Akt/PKB is a serine/threonine kinase that plays an important role in survival when cells are exposed to different apoptotic stimuli. Aberrant activation of Akt/PKB in breast carcinoma is associated with poor prognosis and resistance to endocrine therapy and chemotherapy. The Akt signaling pathway currently attracts considerable attention as a new target for effective therapeutic strategies. We therefore investigated the relationship between activation of Akt and clinicopathologic variables including hormone receptor and HER2/neu status. Breast cancer tissues obtained from 252 patients were utilized for this study. We evaluated Akt activation by immunohistochemical assessment of the expression of phosphorylated Akt (pAkt) at Ser-473. Eighty-four cases (33.3%) were diagnosed as positive for pAkt expression. pAkt was significantly associated with HER2/neu overexpression (p < 0.0001). There was an inverse correlation between pAkt and PR expression (p = 0.0321); however, there was no association between pAkt and ER expression. Survival analysis showed that pAkt positivity was associated with poor disease-free survival in cases with postoperative hormone therapy; however, there was no association in cases without hormone therapy. Our results indicate that Akt activation induced poor prognosis in patients who received adjuvant hormone therapy. This finding suggests that inhibition of the Akt signaling pathway may increase the efficacy of hormone therapy and improve the prognosis of patients who receive adjuvant hormone therapy.

Adult↗