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PubMed2004

Matrix metalloproteinase/tissue inhibitors of matrix metalloproteinase phenotype identifies poor prognosis colorectal cancers.

PURPOSE: The matrix metalloproteinases (MMPs) are a family of proteolytic enzymes involved in tumor invasion; several individual members of which have been implicated in tumor prognosis. These enzymes and their physiologic inhibitors, the tissue inhibitors of matrix metalloproteinases (TIMPs), act in a coordinated manner to form an integrated system. Therefore, to understand their role in tumor invasion, it is necessary to evaluate them collectively. EXPERIMENTAL DESIGN: In this study all of the major members of the matrix metalloproteinase (MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, MT1-MMP and MT2-MMP)/tissue inhibitor of matrix metalloproteinase (TIMP-1, TIMP-2, and TIMP-3) system have been investigated by immunohistochemistry in a series (n = 90) of stage III (Dukes' C) colorectal cancers. An immunohistochemical score based on the intensity of immunoreactivity and proportion of immunoreactive cells was established for each MMP and TIMP. RESULTS: The MMP/TIMP profile defined by hierarchical cluster analysis of the immunohistochemical score identifies a distinct group of colorectal cancers with poor prognosis (log-rank test, 12.22, P = 0.0005). The median survival time of patients in this survival group was 18 months compared with a median survival of 49 months in the "good" survival group. Multivariate analysis showed that this profile was independently the most significant prognostic factor (P = 0.001). CONCLUSIONS: This study has identified that the MMP/TIMP profile is an independent indicator of poor prognosis in colorectal cancer.

Adenocarcinoma↗
PubMed2005

Shc family expression in neuroblastoma: high expression of shcC is associated with a poor prognosis in advanced neuroblastoma.

The biological features and prognosis of neuroblastoma, a neural crest-derived pediatric tumor, are closely associated with expression of the Trk receptor. Because the Shc family proteins (ShcA, ShcB, and ShcC) are adaptors for various receptors, including Trk receptors, and are regulators of neuronal cell development, we speculated that they may play a role in neuroblastoma. Therefore, in this study, we used semiquantitative reverse transcription-PCR to examine the expression of these three genes in 15 neuroblastoma cell lines, an all-trans-retinoic acid-treated neuroblastoma cell line, and 52 tumor samples. In neuroblastoma cell lines and tumor samples, shcA was ubiquitously and highly expressed. Little expression of shcA was observed. Also, shcB was hardly expressed in neuroblastoma cell lines, but its expression in RT-BM-1 cells was enhanced after all-trans-retinoic acid-induced differentiation, and it was highly expressed in low-stage tumors (P = 0.0095). This suggests that ShcB participates in cellular differentiation and may correlate with a favorable prognosis in neuroblastoma. Finally, the expression of shcC was observed in most of the neuroblastoma cell lines and in some stage 4 patients. Patients with a high expression of shcC had a very poor prognosis (P < 0.0001) and amplification of MYCN, and all died within 31 months after diagnosis. Therefore, ShcC seems to be associated with an aggressive tumor phenotype, perhaps by enhancing TrkB signals. Our results suggest that the expressions of shcB and shcC are important biological factors in neuroblastoma and are useful prognostic indicators.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Prognosis and gene expression profiling of 20q13-amplified breast cancers.

PURPOSE: Amplification of chromosomal region 20q13 occurs in breast cancer but remains poorly characterized. EXPERIMENTAL DESIGN: To establish the frequency of 20q13 amplification and select the amplified cases to be studied, we used fluorescence in situ hybridization of bacterial artificial chromosome probes for three 20q13 loci (MYBL2, STK6, ZNF217) on sections of tissue microarrays containing 466 primary carcinoma samples. We used Affymetryx whole-genome DNA microarrays to establish the gene expression profiles of 20q13-amplified tumors and quantitative reverse transcription-PCR to validate the results. RESULTS: We found 36 (8%) 20q13-amplified samples. They were distributed in two types: type 1 tumors showed ZNF217 amplification only, whereas type 2 tumors showed amplification at two or three loci. Examination of the histoclinical features of the amplified tumors showed two strikingly opposite data. First, type 1 tumors were more frequently lymph node-negative tumors but were paradoxically associated with a poor prognosis. Second, type 2 tumors were more frequently lymph node-positive tumors but were paradoxically associated with a good prognosis. Type 1 and type 2 showed different gene expression profiles. No 20q13 gene could be associated with type 1 amplification, whereas several 20q13 genes were overexpressed in type 2 tumors. CONCLUSIONS: Our results suggest that amplified tumors of types 1 and 2 are two distinct entities resulting from two different mechanisms and associated to different prognosis.

Breast Neoplasms↗
PubMed2006

Increased expression of Wiskott-Aldrich syndrome protein family verprolin-homologous protein 2 correlated with poor prognosis of hepatocellular carcinoma.

PURPOSE: Because of its role in cell migration, the Wiskott-Aldrich syndrome protein family verprolin-homologous protein (WAVE) 2 has been implicated in cancer metastasis. Evidence to support such a role of WAVE2 in human cancer, however, is lacking. We thus examined the expression of WAVE2 in hepatocellular carcinoma (HCC) tissues to test whether the levels of WAVE2 expression correlated to the progression of HCC. EXPERIMENTAL DESIGN: Samples of 112 HCC patients were determined immunohistochemically for WAVE2 expression and the correlation of WAVE2 levels with prognosis was analyzed. Among the 112 cases, 31 paired HCC and paracarcinomatous liver tissue specimens were analyzed for WAVE2 levels by reverse transcription-PCR and Western blotting, respectively. RESULTS: Among 112 cases of HCCs, the immunohistochemistry data indicated significant increase of WAVE2 expression levels in 71 cases. Importantly, the increased WAVE2 expression correlated with the multiple tumor nodules (P = 0.008), the absence of capsular formation (P = 0.035), Edmondson-Steiner grade (P = 0.009), vein invasion (P = 0.023), and a shortened median survival time (326 versus 512 days; P = 0.003). Multivariable Cox regression analysis revealed the WAVE2 expression level was an independent factor for prognosis. The immunohistochemistry data were further confirmed by results of reverse transcription-PCR and Western analysis of 31 HCC cases, in which the WAVE2 mRNA and protein in HCC tissues were significantly elevated when compared with paracarcinomatous liver tissue (P < 0.001). CONCLUSIONS: WAVE2 expression is elevated in HCC tissues, which correlates with a poor prognosis, suggesting WAVE2 as a candidate prognostic marker of HCC.

Adolescent↗
PubMed2004

Tissue array-based predictions of pathobiology, prognosis, and response to treatment for renal cell carcinoma therapy.

Renal cell carcinoma is the most lethal of the common urologic malignancies, with approximately 40% of patients eventually dying of cancer progression. Approximately one third of patients present with metastatic disease, and up to 40% treated for localized disease have a recurrence. Historically, clinical factors have been used as prognostic markers for patients with renal cell carcinoma. Recent advances in the understanding of the pathogenesis, behavior, and molecular biology of renal cell carcinoma have paved the way for developments that may enhance early diagnosis, better predict tumor prognosis, and improve survival for renal cell carcinoma patients. Furthermore, reliable predictive factors are essential for the stratification of patients into clinically meaningful categories, which can be used to provide patients with counseling regarding prognosis, select treatment modalities, and determine eligibility for clinical trials. This has led to the creation of integrated staging systems that predict outcome by combining pathological and clinical variables. Although staging has been improved with the development of integrated systems, molecular tumor markers are expected to revolutionize the staging of renal cell carcinoma in the future. The development of methods based on gene and tissue arrays has created a powerful tool for evaluating hundreds to thousands of tumors simultaneously with histologic, immunohistochemical, and chromosomal analyses. Gene array analysis permits rapid molecular profiling, and tissue arrays enable the analysis of protein expression profiles on specimens to determine their potential clinical significance and role in renal cell carcinoma biology. This article reviews the tissue array-based predictors of pathobiology, prognosis, response to treatment, and potential molecular targets for therapy of renal cell carcinoma.

Algorithms↗
PubMed2000

Loss of p27(KIP1) expression predicts poor prognosis in patients with esophageal squamous cell carcinoma.

Immunohistochemical studies of cell cycle-regulating proteins were conducted on tissue samples from 106 patients with esophageal squamous cell carcinoma. Reduction of p27(KIP1) was observed in 41 (39%) cases and was significantly associated with a poor prognosis by univariate and multivariate analyses (p = 0.015). In contrast, p16(INK4) expression was reduced in 55 (52%) of the cases and was not correlated with prognosis. p27(KIP1) was not correlated with the PCNA index, while p16(INK4) expression was inversely correlated with the PCNA index (p = 0.01). The expression of these two proteins was not correlated with the clinicopathological parameters of the patients. Nodal status was shown by univariate analysis (p = 0.01) to be a prognostic factor, and poorly differentiated tumors were significantly associated with a poor prognosis by multivariate analysis (p = 0.027). Thus, reduction of p27(KIP1) plays an important role in the progression of esophageal squamous cell carcinomas and is considered to be an independent prognostic indicator of this disease.

Adult↗
PubMed2000

Prognosis factors in carcinoma of the head of the pancreas.

BACKGROUND: Due to a low survival rate even after a R0 resection of cancer of the head of the pancreas, a strict indication for a pancreaticoduodenectomy seems to be sensible. We have therefore analyzed our patients for possible prognosis factors. METHODS: In a retrospective trial the courses of disease of all patients (1981-1996) with resected histologically proven carcinoma of the head of the pancreas were analyzed. The following patient-specific parameters were evaluated and examined in a single or multivariate analysis of prognosis factors: age, gender, tumor size (T status), lymph node involvement (N status), dimension of resection, operation method, time of operation, morbidity, clinic lethality and survival rate. RESULTS: Between 1981 and 1996, 500 patients with ductal adenocarcinoma of the head of the pancreas were treated surgically. The rate of resection increased from 32.1% (1981-1986) to 37.8% (1991-1996) whereas the mortality rate decreased from 13.3 to 7.3%. The 5-year survival rate after resection was 11.8% with a median survival time of 13.8 months. In a multivariate analysis, only small tumors (T1, p < 0.016), the R0 status (p < 0.017) and the resection had a significant influence on the survival rate. CONCLUSION: Prognosis factors in the treatment of pancreatic cancer were tumor size (T1), tumor resection and R0 status.

Adenocarcinoma↗
PubMed2000

Quality of life of patients with newly diagnosed poor prognosis M1 prostate cancer undergoing orchiectomy without or with mitomycin C. Results from the EORTC Phase-III trial 30893.

OBJECTIVES: To compare the quality of life (QL) of patients with poor prognosis M1 prostate cancer treated with orchiectomy alone (ORCH) or orchiectomy combined with adjuvant mitomycin C (MMC; 15 mg/m(2) i.v. q 6 weeks: ORCH+MMC; EORTC trial 30893). METHODS: Patients with newly diagnosed M1 poor prognosis prostate cancer completed a truncated version of the EORTC QLQ-C30 (V 1.0) at randomization (baseline) and every 6-12 weeks thereafter until going off the protocol. Five ad hoc questions assessing lower urinary tract symptoms were included in the QL questionnaire. RESULTS: At least one QL form was completed by 177 of the 189 patients included in the trial, with baseline questionnaires available for 113 patients (ORCH n = 52; ORCH+MMC n = 61). In both arms, pain and urinary dysfunction improved during treatment. Compared with patients from the ORCH arm, the use of adjuvant MMC was associated with a significant reduction in global health status/QL and with impairment in 7 of 11 QL dimensions covered by the questionnaire. Some improvement in QL was observed after discontinuation of MMC. A survival benefit was not observed in the ORCH+MMC arm. CONCLUSIONS: Intravenous MMC (15 mg/m(2) q 6 weeks) cannot be recommended as adjuvant treatment in M1 poor prognosis prostate cancer due to its negative impact on QL and lack of efficacy. In general, QL assessments should be mandatory when adjuvant chemotherapy is evaluated in patients with metastatic prostate cancer.

Aged↗
PubMed1998

[Menstrual cycle anomalies in young girls--prognosis concerning later fertility].

Menstrual disorders in adolescents should be investigated promptly to avoid or alleviate possible long-term sequelae, including impaired fertility. Patients with uterine amenorrhea cannot become pregnant. The prognosis for later fertility in patients with oligoamenorrheas depends on the pathogenesis and degree of the condition. Hypothalamic oligoamenorrheas generally resolve when the offending stimuli are removed, and the prognosis for future fertility is good. In patients with pituitary lesions, even those with complete loss of pituitary function, pregnancies can be achieved and maintained with exogenous gonadotropins. Menstrual disorders due to hyperprolactinemia can be treated effectively. Hyperandrogenemic oligoamenorrheas, especially the polycystic ovary syndrome, are common. Future fertility has been improved with preventive measures in adolescence and later interventions. Patients with primary ovarian insufficiency and persisting hypergonadotropic amenorrhea have a poor prognosis. A new aspect is the restitution of ovarian function after treatments for malignant diseases.

Adolescent↗
PubMed2000

Metabolic and clinical markers of prognosis in the era of CT imaging in children with acute epidural hematomas.

Acute epidural hematoma (AEH), a relatively common complication of head injury in children, persists in bearing high morbidity and mortality. Early establishment of prognosis could guide optimal patient allocation, and early identification of predictive signs could assist in choosing appropriate therapeutic interventions. This study aimed to delineate expeditiously obtainable prognostic markers for determining outcome in a subset of children with AEH. We reviewed our 11-year experience with 61 consecutive children <16 years old with head trauma and isolated AEH. Treatment followed a standard advanced trauma life support protocol. A medical history was obtained, and all patients underwent neurosurgical and physical evaluations. CT scans were performed, as were laboratory tests which included arterial blood gases, glucose, electrolytes (K(+), Na(+)), hemoglobin and coagulation studies. Evaluation of the data collected on cause of injury, interval between trauma occurrence and presentation, clinical symptoms, Glasgow Coma Scale (GCS) scores, vital signs, laboratory test results, physical findings and surgical versus conservative management revealed that the best single predictors of outcome following AEH were the GCS and focal neurological deficits. Of all laboratory data obtained on admission, the blood potassium, pH and glucose test results correlated significantly with prognosis. Prognosis can be adequately and expeditiously estimated by selected markers within a comprehensive evaluation of children with AEH.

Acute Disease↗
PubMedDate not supplied

Immunohistochemical detection of H-ras protooncoprotein p21 indicates favorable prognosis in node-negative breast cancer patients.

We tested primary breast carcinoma tissues from 297 patients using a monoclonal antibody (clone 235-1.7.1.) for the expression of p21(ras). 58% of tumors were p21(ras)-positive. When calculated in a univariate fashion, p21 expression correlated with proliferation activity (proliferating cell nuclear antigen) only. Using the log-rank test (median observation time 94 months) a significantly worse prognosis (disease-free survival, overall survival) relation was found with larger tumors, nodal involvement, anaplasia, rising proliferation activity, and lack of steroid receptors. Detection of p21(ras) correlated with a more favorable prognosis but only in node-negative patients. Stepwise correlation according to the Cox hazard model ranked p21 expression as a most significant predictor of prognosis second only to nodal status. These data suggest that detection of p21(ras) indicates the presence of a parameter which may act as tumor suppressor and benefit patients' survival.

Adult↗
PubMed2002

Validation of a central review board of staging prior to surgery for non-small-cell lung cancer--impact on prognosis: a multicenter study.

BACKGROUND: In non-small-cell lung cancer (NSCLC), the evaluation of anatomic tumor extension [tumor, node, metastasis (TNM) stage] is indispensable for the exchange of scientific information or determining prognosis. OBJECTIVE: To quantify changes in TNM stages (numerical migration) and survival (prognostic migration) resulting from the application of classificatory certainty criteria to patients with NSCLC who had undergone surgical treatment. METHODS: The study population included 1,844 patients registered by the Bronchogenic Carcinoma Cooperative Group of the Spanish Society of Pneumology and Thoracic Surgery (GCCB-S). For every patient, two evaluations were made of each component of the TNM classification: an initial classification, defined by a local representative, and a confirmed classification resulting from the application of stricter classificatory criteria by the GCCB-S Central Review Board. RESULTS: The results revealed scant numerical migration in the cT category (11.5% of the study population) and a general tendency toward a downstaging. In contrast, the initial cN1 category experienced a complete numerical migration and the initial cN2 category a very large numerical migration (from 200 to 22 cases). In the small group of patients for whom there was a classificatory change in cT (n = 212), the migration for the cT2 category was accompanied by a less favorable prognosis (p = 0.039, log-rank test). However, the migration of this small subset of patients did not affect the general prognosis of the study population for cT2. In cN2, the 3-year survival rate migrated from 0.42 to 0.29. CONCLUSIONS: Numerical migration resulting from the application of stricter classificatory criteria was relevant, but had little, although unfavorable, global prognostic impact.

Biopsy, Needle↗
PubMed2003

Loss of p27 expression is associated with poor prognosis in stage I-II pancreatic cancer.

OBJECTIVE: p27 is a cyclin-dependent kinase inhibitor that prevents progression of the cell cycle from G1 phase. Postranscriptional loss of p27 correlates with poor prognosis in various solid tumors. In pancreatic cancer, the loss of p27 expression has been correlated with high tumor grade and advanced clinical stage, but data on its prognostic value are lacking. METHOD: In this retrospective study, the association between immunohistochemical p27 expression and prognosis was evaluated in 147 patients with pancreatic cancer using a commercial anti-Kip1/p27 monoclonal antibody. RESULT: p27 expression was generally low; in 103 of the 147 pancreatic cancer tumors examined, no nuclear staining was observed and in only 5 specimens did more than 50% of the nuclei stain, probably reflecting the aggressive nature of the disease. Loss of p27 expression was associated with poor prognosis in stage I-II pancreatic adenocarcinoma; the 5-year survival for p27 negative patients was 3.6% compared with 20% for p27-positive patients (p = 0.03). In a multivariate survival analysis in patients with stage I-II disease, p27 (HR 1.8) was a significant prognostic factor, independent of grade (RR 2.9). There was no association between p27 and other clinical variables. In conclusion, tissue expression of p27 is a significant predictor of 5-year survival in stage I-II pancreatic adenocarcinoma.

Aged↗
PubMed2004

CA19-9 as a serum marker for poor prognosis in urothelial carcinoma.

INTRODUCTION: To evaluate the role of serum carbohydrate antigen 19-9 (CA19-9) in the prognosis and follow-up evaluation of patients with urothelial carcinoma, the authors studied the association of the serum level and positive rate with clinical features such as infiltration and metastasis in 164 patients admitted to the authors' department. PATIENTS AND METHODS: This study included 164 cases of patients with urohelial carcinoma. The absolute value of the serum CA19-9 level and its positive rate were tested. Simple variant analysis and logistic regression analysis were used for estimation of statistical significance. Kaplan-Meier's test and Cox's proportional hazard model were used for analysis of survival. RESULTS: Significant differences in the serum CA19-9 levels were found with regard to the following parameters: the presence or absence of metastasis, clinical stage, depth of invasion, and degree of differentiation. The positive rate displayed a significant difference only for the presence or absence of metastasis. With regard to the presence of metastasis, serum CA19-9 was a significant risk factor along with depth of invasion in logistic regression analysis. Comparison of the survival rate indicated the prognosis to be significantly poor in the positive group and serum CA19-9 was regarded to be a prognostic risk factor in analysis via the regression model. CONCLUSIONS: Serum CA19-9 is thought to serve as a significant marker for advanced cancer and tumors with highly malignant potential and is useful for predicting prognosis of the disease.

Adult↗
PubMed2004

Impact of different diagnostic criteria on prognosis of delirium: a prospective study.

A 2-year follow-up study was performed to compare the prognosis of delirium defined according to 4 different diagnostic classifications (DSM-III, DSM-III-R, DSM-IV and ICD-10 clinical criteria) among 425 elderly geriatric hospital patients and nursing home residents. The proportion of delirium varied from 24.9% (DSM-IV) to 10.1% (ICD-10). The prognoses were similar particularly according to all DSM classifications: 31.3-36.3% of the delirious patients died within 1 year and 57.8-62.5% within 2 years. The number of subjects diagnosed as delirious according to the ICD-10 was small, and their prognosis did not differ significantly from the others either. The DSM-IV has simplified the criteria of delirium. It identifies new, acutely ill and relatively nondependent subjects as delirious who share the poor prognosis of patients diagnosed with the previous criteria.

Aged↗
PubMed2004

Characteristics and prognosis of Chinese patients with anti-glomerular basement membrane disease.

BACKGROUND: Patients with anti-glomerular basement membrane (GBM) disease were predominantly reported in Caucasian population and reports from Chinese were lacking. The general picture of Chinese patients with anti-GBM disease was still unclear. This study is to investigate the characteristics and prognosis of Chinese patients with anti-GBM disease. METHODS: Data from 105 patients with anti-GBM disease diagnosed in our hospital, between 1997 and 2002, were analyzed retrospectively. All the 105 sera were screened by enzyme-linked immunosorbent assay (ELISA) using highly purified bovine alpha(IV)NC1 as solid phase ligands. Clinical and pathological data of 69 patients with complete clinical remission (n = 5), partial remission (n = 10), and treatment failure (n = 54) were compared and the prognostic factors were evaluated. RESULTS: Patients increased chronologically and three quarters of the 105 patients were diagnosed in the last 3 years. Most of the patients were between 20 and 29 years (n = 31) and a smaller second peak was found in patients over 60 years. 25/105 (24%) were also ANCA-positive. Patients with both anti-GBM antibodies and ANCA positive were elder (50 +/- 19 vs. 34 +/- 15 years, p < 0.01) and female predominant (15/25 vs. 16/80, p < 0.05). 56/97 (58%) patients presented as Goodpasture syndrome, 40/97 (41%) patients presented as rapidly progressive glomerulonephritis and one patient had pulmonary hemorrhage only. The following factors predict poor prognosis: (1) serum creatinine more than 600 micromol/l on diagnosis (p < 0.01); (2) oliguria or anuria on diagnosis (p < 0.01); (3) a high percentage (>85%) of glomeruli had crescents (p < 0.01), and (4) renal involvement before pulmonary hemorrhage (p < 0.05). Patients with serum creatinine over 600 micromol/l on diagnosis had higher levels of anti-GBM antibodies (106 +/- 48% vs. 73 +/- 40%, p < 0.01). Intensive plasma exchange therapy predicts a better prognosis in the patients with serum creatinine less than 600 mumol/l (p < 0.05). CONCLUSIONS: Anti-GBM disease is not rare in China and behaves similarly to elsewhere. Early diagnosis and intensive plasmapheresis might be the most promising approaches to improve the outcome.

Adolescent↗
PubMed2005

Immunohistochemical expression of multidrug resistance proteins as a predictor of poor response to chemotherapy and prognosis in patients with nodal diffuse large B-cell lymphoma.

BACKGROUND/AIMS: The aim of this study was to determine whether expression of P-glycoprotein (P-gp), multidrug-resistance-related protein 1 (MRP1), and lung resistance protein (LRP) was related to the response to induction chemotherapy and prognosis in untreated diffuse large B-cell lymphoma (DLBCL). METHODS: We assessed immunohistochemical expression of P-gp, MRP1 and LRP, using formalin-fixed and paraffin-embedded specimens of lymph node in 41 patients with DLBCL. Association between expression of these three proteins and their impact on clinical outcome and prognosis was statistically evaluated. RESULTS: P-gp was positive in 37% of subjects, MRP1 in 63%, and LRP in 68%. The complete remission rates achieved in the group expressing these multidrug resistance (MDR) proteins was significantly lower than in the group not expressing them (20 versus 58%; p = 0.025 in P-gp, 23 versus 80%; p < 0.001 in MRP1 and 32 versus 69%, p = 0.043 in LRP, respectively). Furthermore, the patients expressing LRP had a shorter overall survival rate than those that did not (median of 26 months versus median not reached; p = 0.013). CONCLUSIONS: These findings suggest that the three MDR proteins are important predictive factors for the clinical outcome and prognosis in patients with DLBCL.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1987

Perinatal distress and prognosis of psychotic illness.

The medical histories of a group of 511 patients hospitalized for schizophrenia were examined for the occurrence of perinatal distress. These patients were part of a 40-year follow-up study, so that their prognostic outcome was known at the time of this study. In this way, 200 cases of chronic schizophrenia were compared with 311 cases of psychotics with good prognosis. It was found that a history of perinatal distress was much more common in the poor prognosis group than in the good prognosis group. This difference could not be accounted for by age or family history of psychiatric illness.

Adult↗