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Prognostic factors in ovarian cancer.

There is obvious merit in being able to accurately predict outcome and tailor treatment according to individual risk and potential for benefit. Epithelial ovarian cancers are characterized by a broad spectrum of biological behavior ranging from tumors that have an excellent prognosis and high likelihood of cure to those that progress rapidly and have a very poor prognosis. This wide clinical spectrum is partly reflected by a number of clinicopathological prognostic variables which include International Federation of Gynecology and Obstetrics stage, histologic subtype and grade, volume of residual tumor remaining after surgical resection, performance status, and age. There has been increasing interest by many groups to incorporate the independent prognostic variables into multivariate models that could better predict outcome. This approach does appear to allow the identification of different prognostic subsets and requires confirmation in prospective studies. There has been, and there continues to be a lot of effort in identifying new prognostic factors that have a biologic rationale and these will be discussed. Most of these new prognostic factors have not been subjected to rigorous testing and this will be clearly necessary before they find clinical application. This is an area that is rapidly evolving with the increased understanding of the molecular basis for ovarian carcinogenesis and progression coupled with technological advances such as DNA arrays and automated polymerase chain reaction. We are at the threshold of developing a new and more objective as well as rational approach to predict prognosis and response to therapy.

Drug Resistance, Neoplasm↗

Prognostic factors in renal cell carcinoma.

In this study we evaluated some morphological and clinical prognostic factors in 166 patients with renal cell carcinoma (RCC). Patients' ages, sex and localization of the tumor had no effect on survival. Tumor diameter and the weight of the nephrectomy specimen revealed prognostic value. Stage of the tumor, especially the presence of metastasis, is the most important prognostic factor for RCC (p < 0.001). Tumor grade had prognostic value (p = 0.0146). The survival difference between cell types was not significant (p > 0.05). Renal vein invasion, the presence of pseudocapsules and tumor in the intravascular space, mitotic rate, the presence and the number of lymphocytes and macrophages, along with the presence of calcifications had no prognostic value (p > 0.05). The presence of necrotic areas was significant (p = 0.0102). The patients with "infiltrative growth pattern" showed poorer prognosis than patients with "pushing type growth pattern", regardless of the existence of a pseudo capsule (p = 0.0045).

Adenocarcinoma, Clear Cell↗

Serum albumin: a prognostic indicator in patients with colorectal cancer.

Various prognostic factors for survival have been identified in patients with colorectal cancer. However, although it has been suggested that the pre-treatment serum albumin concentration is a prognostic indicator in certain malignant diseases (melanoma, prostate cancer, leukaemia), its value in patients with colorectal cancer remains unclear. This study investigated the prognostic value of serum albumin in this patient group. A total of 431 patients presenting to the Professorial Surgical Unit between 1972 and 1985 were analysed in this study. Using the Cox proportional hazard model, age, tumour stage (Dukes' stage) and tumour differentiation were shown to be independent prognostic factors for survival in patients with localized colorectal cancer. In addition, the pre-treatment serum albumin concentration was found to be an independent prognostic indicator. This is the first such documentation for patients with 'curable' colorectal cancer.

Adult↗

The prognostic value of alpha-thymosins in breast cancer.

The prognosis of breast cancer is of major clinical importance and several histopathological, biochemical and immunological variables have been reported to be useful prognostic factors. In the present study, we investigated the clinical significance of the levels of alpha-thymosins in relation to established prognostic factors, both in breast cancer and non-malignant breast lesions, alpha-thymosin levels were measured in breast tissue extracts by specific radioimmunoassays (RIAs) developed for human prothymosin alpha (ProT alpha) and parathymosin alpha (ParaT alpha) and were found to be significantly higher (up to 17.2-fold) in malignant but not in benign breast lesions, as compared to the values of the neighbouring tissues. When alpha-thymosin levels of the tumor samples were correlated with various known prognostic parameters a statistically significant correlation (p < 0.05) was observed between the levels of ProT alpha in malignant tissues to the grade of cancer and the lymph node status of the patient. An association between ProT alpha levels with increase in risk of death from breast cancer was also noticed. These results suggest that the expression of alpha-thymosins in human breast cancer a) depends on the proliferation status of the tumor, b) associates with established prognostic factors describing the metastatic potential of the tumor and c) is related to the overall survival of the patient. The fact that such relationships hold only for cancer tissues encourages the future use of alpha-thymosins as potent prognostic factors in breast cancer.

Adult↗

Prognostic impact of morphometric nuclear grade of endometrial carcinoma.

BACKGROUND: The identification of high risk patients with endometrial carcinoma is considered essential for individualized therapy to improve prognosis and avoid overtreatment. The goal of the current study was to investigate the prognostic value of nuclear morphometry, particularly for patients with localized endometrial carcinoma. METHODS: In a prospective study including 115 patients primarily treated for endometrial carcinoma at Haukeland University Hospital in Bergen, Norway between 1981-1990, data regarding clinical variables, histologic type, histologic grade, DNA index, estrogen and progesterone receptor concentration and nuclear morphometry were collected. The median follow-up period for the survivors was 9 years (range, 5-15 years). RESULTS: International Federation of Gynecology and Obstetrics (FIGO) stage, histologic type, histologic grade (World Health Organization), DNA index, progesterone receptor concentration, mean nuclear area, greatest and smallest nuclear diameter, nuclear perimeter, and standard deviation to mean nuclear area all influenced survival significantly in univariate analyses. In multivariate analyses, FIGO stage and morphometrically determined mean nuclear size were identified as independent prognostic factors, whereas histologic grade had borderline significance. Histologic type, DNA index, progesterone receptor concentration, and standard deviation of mean nuclear area were not significantly associated with prognosis. The nuclear perimeter was identified as the most powerful prognostic morphometric factor, and in a separate multivariate analysis that included patients with localized disease only, it was also an independent prognostic factor. This also was the case for the subgroup of patients with endometrioid carcinoma, adenoacanthoma, or adenosquamous carcinoma. CONCLUSIONS: Morphometric nuclear grade was a stronger prognostic factor than subjective histologic grade, histologic type, DNA index, and hormone receptor concentration in endometrial carcinoma patients, including those patients with localized disease.

Adenocarcinoma↗

[Prognostic factors in low-grade lymphoma].

PURPOSE: Prognostic factors in low grade non-Hodgkin's lymphoma (LGL) are not well established. The aim of this study is to investigate prognostic factors on LGL treated in our institution during the last decade. PATIENTS AND METHODS: The study was carried out on 70 cases of newly diagnosed LGL, most treated with CVP or clorambucil and prednisone. The median follow-up was 37 months (1-132). Variables reported as prognostic factors in previous series were subjected to bivariate and multivariate analysis. RESULTS: Relevant clinical features were: Ann Arbor III-IV stage 74%, ECOG > or = 2-17%, bone marrow involvement 60% and large tumor burden according to MD Anderson criteria 21%. Complete response (CR) was achieved in 50% and partial response in 29%. In bivariate analysis factors related with poor CR were B symptoms, large tumor burden, high LDH and more than one extranodal site involvement. Logistic regression showed that large tumor burden (p = 0.02; OR = 0.07) and B symptoms (p = 0.07; OR = 0.14) were the best prognostic factors of poor CR. Five year global survival (GS) was 55%, with a median of 76 months. In univariate analysis factors related with GS were ECOG > or = 2, B symptoms, bulky, large tumor burden, retroperitoneo involvement and absence of CR. In multivariate analysis the only factor related with poor GS was large tumor burden (p < 0.00001; RR = 5.93). When therapeutic response was included in the model, absence of CR (p = 0.008; RR = 3.40) and large tumour burden (p = 0.005; RR = 3.86) were the factors selected. CONCLUSIONS: In LGL tumor burden was the most important prognostic variable. Tumor response showed less importance than in high grade lymphomas.

Adult↗

Prognostic patch testing: the other kind of patch test.

Prognostic patch testing differs from diagnostic patch testing. Clinicians routinely perform diagnostic patch testing, but prognotic patch testing is the province of corporate research and development departments and, in the United States, contract laboratories. The three types of prognostic patch testing are described and referenced in the scientific and medical literature. A comparison among the three types of prognostic patch testing and diagnostic patch testing is provided. In addition, the variables in both prognostic and diagnostic patch testing are listed, as well as the types of ingredients and products routinely tested in prognostic patch testing.

Consumer Product Safety↗

Prognostic value of pleural effusion in patients with non-small cell lung cancer.

This study was performed to determine whether pleural effusion in patients with advanced non-small cell lung cancer (NSCLC) has a negative impact on survival. We evaluated 12 prognostic factors in 197 patients with stage IIIB or IV NSCLC. Each factor was dichotomized, and survival curves calculated by the Kaplan-Meier technique were compared using the log-rank test. The Cox proportional hazards regression model was used to confirm the significance of each prognostic factor selected by univariate analysis. We compared the survival times for stage IIIB with pleural effusion with those of stage IIIB without effusion and stage IV. To determine the impact of the cytological results of the effusion on survival, we compared the survival times for cytologically positive and negative effusions. Univariate analysis identified eight significant prognostic factors: pleural effusion, node status, stage, performance status, weight loss, hemoglobin, albumin, and lactate dehydrogenase. Pleural effusion was selected as a prognostic factor in the multivariate analysis, together with stage, performance status, albumin, and node status. Median survival times for stage IIIB without effusion, stage IIIB with effusion, and stage IV were 15.3, 7.5, and 5.5 months, respectively (P < 0.0001). Survival time for stage IIIB with effusion was significantly different from that of stage IIIB without effusion (P = 0.0129) but not from that of stage IV (P = 0.0797). Among patients with effusion, no significant difference in survival time was observed between cytologically positive and negative effusions. We conclude that pleural effusion in advanced NSCLC is a prognostic factor. Survival time for stage IIIB with pleural effusion is more similar to that of stage IV rather than that of stage IIIB without effusion.

Adult↗

Lack of prognostic significance of histological grade in node-negative invasive breast carcinoma.

Histological grade (HG), as modified by Elston and Ellis (Histopathology, 19: 403-410, 1991), was shown to be a significant prognostic indicator in a large group of women with invasive breast cancer, who had node-negative as well as node-positive tumors and included special types of breast cancer. The aim of this study was to determine the utility of HG as a prognostic indicator in node-negative invasive breast cancer, no special type (NN-BCA-NST), which represents the majority of cases seen in clinical practice. One hundred eighty-two women with NN-BCA-NST and who had 28-106 months follow-up (mean, 73 months; median, 71 months) were entered in the study. Bilateral and multifocal cancers, and cancers with distant metastases, were excluded. Nuclear grade (NG), tubule formation (TF), mitotic index (MI), and HG were determined and scored as described by Elston and Ellis (Histopathology, 19: 403-410, 1991). Survival analysis was performed by the Kaplan-Meier method and the log-rank test. Regression analysis was used to determine the relationship between NG, TF, and MI. There was significant correlation between NG and MI (R = 0.667, P < 0.0001) and between TF and MI (R = 0.416, P < 0.0001). NG, TF, MI, and HG did not have significant prognostic value (P = 0.3771, P = 0.7972, P = 0.2953, and P = 0.7946, respectively). HG was of no significant prognostic value even after women who received adjuvant therapy were excluded from the analysis (P = 0.3917). Our data show that the HG is not a reliable prognostic indicator in NN-BCA-NST.

Age Factors↗

Prognostic significance of cyclin D1 and retinoblastoma expression in combination with p53 abnormalities in primary, resected non-small cell lung cancers.

This study was conducted to evaluate the prognostic significance of cyclin D1 and retinoblastoma (Rb) expression in combination with abnormal p53 accumulation in primary, resected non-small cell lung cancers (NSCLCs). We evaluated immunohistochemically the expression of cyclin D1 and Rb in 208 NSCLC patients whose resections were consecutively performed between January 1984 and December 1988 and determined their prognostic significance by comparison with follow-up data. Expression of cyclin D1 and Rb was detected immunohistochemically in 39 and 80% of the 208 NSCLCs, respectively. The Kaplan-Meier survival curve demonstrated that absence of cyclin D1 expression was significantly associated with shortened survival (P = 0.01 by the log-rank test), particularly in adenocarcinomas (n = 100; P = 0.004). Expression status of the Rb protein was not significantly associated with clinical outcome in any of the cohorts. The predictive power of these prognosticators was also assessed in combination with findings for abnormal p53 accumulation by multivariate analysis using the Cox proportional hazards modeling. Patients with cyclin D1-negative tumors had a significantly greater risk of earlier death than those with cyclin D1-positive tumors (risk ratio, 1.61; P = 0.03), particularly in adenocarcinomas (risk ratio, 2.49; P = 0.002). Cases showing abnormal p53 accumulation tended to have a shortened survival only when the tumors were adenocarcinomas (risk ratio, 1.75; P = 0.06). Absence of cyclin D1 expression may be a useful prognosticator for shortened survival in primary, resected NSCLCs with particular significance for adenocarcinomas. In contrast, Rb expression status is not a useful prognostic factor for any type of NSCLC.

Adenocarcinoma↗

Proteases as prognostic markers in cancer.

It is the ability to invade and metastasize that ultimately determines the prognosis in cancer. Comprising one of the key groups of molecules involved in invasion and metastasis are proteases such as urokinase plasminogen activator and cathepsins B, D, and L, as well as various metalloproteases. These proteases catalyze degradation of the interstitial matrix and basement membranes, allowing cancer cells to invade locally and metastasize to distant sites. If proteases are directly and causally involved in cancer spread, they have the potential to be new prognostic markers in cancer. One of the best examples of a correlation between high levels of a protease in a primary tumor and poor prognosis is urokinase plasminogen activation in breast cancer. In this malignancy, the urokinase plasminogen activator is a strong and independent prognostic marker and may be a marker for axillary node-negative disease. The urokinase plasminogen activator may also be a prognostic marker in other cancers such as gastric, colorectal, lung, bladder, cervical, and ovarian cancers. In a number of studies, cathepsin D has been shown to be a prognostic factor in breast cancer. However, results with cathepsin D, especially when immunocytochemistry is used for its detection, are conflicting. Levels of cathepsin B, cathepsin L, and certain metalloproteases may also supply prognostic data in certain cancers, but results with these proteases are still preliminary.

Animals↗

The fucosylation index of alpha-fetoprotein as a possible prognostic indicator for patients with hepatocellular carcinoma.

BACKGROUND: The aim of this study was to elucidate the usefulness of measuring the fucosylation index (FI) of alpha-fetoprotein (AFP) before the initiation of therapy as a new prognostic indicator for patients with hepatocellular carcinoma (HCC). METHODS: One hundred twelve patients with HCC who underwent transcatheter arterial embolization, chemoembolization, and/or percutaneous ethanol injection were examined in the current study. FI was determined by crossed immunoaffino-electrophoresis in the presence of Lens culinaris agglutinin. RESULTS: When the tentative discriminating value of FI was set at 18%, the mean survival rate for the group whose FI was higher than 18% was significantly lower than that for the group whose FI was equal to or less than 18%, according to the generalized Wilcoxon test (P = 0.0117) and the log rank test (P = 0.0183). The survival rate for HCC patients with AFP concentrations of more than 200 ng/mL was also significantly lower than that for patients with AFP in the range of 21-200 ng/mL, according to the generalized Wilcoxon test (P = 0.0017) and the log rank test (P = 0.0018). When FI was combined with AFP concentration, a highly significant difference was observed between the group with FI >18% and AFP >200 ng/mL and another group with FI < or =18% and AFP < or =200 ng/mL, as determined by the generalized Wilcoxon test (P < 0.0001) and the log rank test (P = 0.0003). An analysis of multiple covariates in the prognostic factors with the Cox proportional hazards model showed that FI was one of the independent prognostic factors. CONCLUSIONS: The current study indicates that measuring FI from sera before the initiation of treatment serves as a new prognostic factor and may improve prognostic estimates and appraisal of therapeutic outcomes for patients with HCC.

Analysis of Variance↗

Overview of prognostic factors in non-Hodgkin's lymphoma.

The non-Hodgkin's lymphomas are a biologically heterogeneous group of diseases with varying clinical presentations and outcomes. A number of studies have identified variables that carried independent prognostic significance. Although several staging systems had evolved that incorporated these prognostic variables, they were still unable to predict outcome. Ideally, the object of a staging system is to predict the likelihood of treatment response, time to progression or disease-free survival, and overall survival, and to provide a way to compare the outcome of similar groups of patients among various clinical trials. The need for such a system led to the creation of prognostic models such as the M.D. Anderson Tumor Score and, more recently, the International Prognostic Index. These prognostic models may identify those patients at highest risk for treatment failure, thereby identifying those patients who may require different therapeutic approaches.

Biomarkers, Tumor↗

The FRISC experience with troponin T. Use as decision tool and comparison with other prognostic markers.

Early prognostic evaluation is essential for the application of appropriate treatment and further management in the heterogeneous population with unstable coronary artery disease. Among the variety of prognostic indicators that have been suggested, biochemical markers of myocardial damage, especially the troponins, have gained increasing interest. The FRISC troponin T (TnT) substudy has validated and provided additional insights into the use of biochemical markers for prognostic evaluation. Nine hundred and seventy-eight patients were enrolled and followed for 5 months. An increase in the rate of cardiac death or myocardial infarction was seen during follow-up, with increasing levels of TnT. The TnT level separated low and high risk patients better than the conventional division of unstable angina and myocardial infarction. In the comparison with other early available risk indicators TnT was an independent risk indicator and gave additive prognostic information to both inclusion ECG and the result of a predischarge exercise test. TnT was superior to CK-MB for risk stratification, while TnT and troponin I showed comparable results. In patients with elevated TnT, treatment with dalteparin significantly decreased the risk for death or myocardial infarction compared to placebo, while there was no benefit from dalteparin in patients without Tn-T elevation. Based on the experiences of the FRISC study and the literature we suggest that the use of troponins should be included in the diagnostic and prognostic evaluation of patients with suspicion of unstable coronary artery disease.

Aged↗

Relevance of the expression of bcl-2 in combination with p53 as a prognostic factor in breast cancer.

BACKGROUND: Both the proto-oncogene bcl-2 and the tumour suppressor gene p53 are involved in the regulation of apoptosis. PATIENTS AND METHODS: We have investigated the prognostic value of the immunohistochemical expression of p53 and bcl-2 separately and in combination in a group of 345 breast cancer patients from one hospital with a long median follow-up of more than 10 years. RESULTS: Bcl-2 expression was not a prognostic factor. p53 was an independent prognostic factor for overall survival (p = 0.005) and for post-relapse survival (p = 0.006). Looking at bcl-2/p53 subgroups in the bcl-2 positive subgroup there was a large difference in both disease-free and overall survival between p53 negative and p53 positive patients. In the bcl-2 negative subgroup the p53 status was not a prognostic factor at all. CONCLUSIONS: p53 is an independent prognostic factor for overall survival and post-relapse survival. However, p53 status is only important in the bcl-2 positive subgroup.

Adult↗

Prognostic factors in head and neck oncology: a critical appraisal for use in clinical practice.

BACKGROUND: An ideal prognostic factor would provide information about the biological behaviour of a tumour, permitting the prediction of the outcome and response to therapy. Nowadays there is a considerable confusion concerning the value, significance and use of the know prognostic factors in head and neck cancer. MATERIAL AND METHODS: A meta-analysis of works published in literature between 1993 and August 1997 on prognostic factors in head and neck oncology was carried out. RESULTS: Prognostic factors were analysed and classified according to Wennenberg in the following groups: patient-related factors, tumour-related factors and factors predicting response to therapy. CONCLUSIONS: We propose a classification of prognostic factors in head and neck cancer according to their significance and reliability: factors of proven significance and experimental factors. This classification might be useful to select guidelines to use in clinical practice.

Biomarkers, Tumor↗

Identification of key genes related to bone metastasis of breast cancer using bioinformatics methods and construction of a prognostic model.

Breast cancer (BC) ranks among the most prevalent cancers in females, with bone metastasis significantly compromising patients' quality of life and survival rates. Enhancing our comprehension of BC bone metastasis mechanisms at the molecular level holds promise for improving BC treatment and prognosis. Leveraging bioinformatics tools, we integrated multiple datasets, conducted comprehensive analyses across various databases, identified biomarkers associated with BC bone metastasis, and constructed a prognostic model. Firstly, 3 BC bone metastasis-related datasets were downloaded from gene expression omnibus, the data were merged, and batch effects were removed, followed by identification of differentially expressed genes (DEGs). Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the DEGs. A protein-protein interaction network was constructed using the STRING database to screen hub genes. Then, survival analysis of hub genes was performed using the Cancer Genome Atlas (TCGA) database. A prognostic model was constructed using key genes with survival differences, and the model was evaluated. Two hundred ninety-two DEGs were identified. Gene ontology and KEGG pathway enrichment analysis yielded 769 biological processes (BPs), 78 cellular components, 43 molecular functions, and 50 KEGG pathways. Fifteen hub genes were selected from the protein-protein interaction network. Survival analysis revealed 6 genes related to BC survival. The prognostic model identified 4 genes with important predictive value for BC prognosis. Our study utilized bioinformatics analysis to identify a series of DEGs related to BC bone metastasis. Based on further selection of hub genes, we constructed a relatively ideal prognostic model for BC, and identified 4 genes (DLGAP5, TPX2, PLK1, and CENPN) with valuable predictive value for BC prognosis.

Humans↗

MS4A3 as a potential prognostic biomarker for colon cancer: integrated analysis of expression patterns and immune cell infiltration.

BACKGROUND: Membrane Spanning 4-Domains A3 (MS4A3) has been confirmed to possess significant tumor-suppressive potential in various malignancies. However, its expression characteristics and clinical prognostic value in colon cancer (CC) still lack systematic and in-depth investigation. This study aimed to systematically investigate the expression pattern, prognostic value, immune microenvironment association, and biological function of MS4A3 in CC through integrated bioinformatics analyses and experimental validation. METHODS: This study utilized The Cancer Genome Atlas-Colon Adenocarcinoma (TCGA-COAD) cohort to screen for genes significantly associated with CC and combined multiple independent Gene Expression Omnibus (GEO) datasets to validate the expression patterns and prognostic significance of MS4A3. Key biological pathways were identified through gene set enrichment analysis (GSEA), and tumor immune infiltration characteristics were evaluated using the CIBERSORT algorithm. Additionally, the expression of MS4A3 and its impacts on cellular functions were validated at the cellular level through quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, Cell Counting Kit-8 (CCK-8), EdU, Transwell, and TUNEL assays. RESULTS: Analysis of public datasets revealed that MS4A3 is significantly downregulated in CC tissues, and its low expression is an independent risk factor for shortened overall survival (OS). GSEA indicated that MS4A3 downregulation is closely associated with the aberrant activation of the pentose phosphate pathway. Immune infiltration analysis showed that low MS4A3 expression is closely linked to the enrichment of M2 macrophages and neutrophils, as well as the upregulation of multiple immune checkpoint genes. In vitro experiments further confirmed that MS4A3 was lowly expressed in CC cell lines. Its overexpression significantly inhibited CC cell viability, proliferation, migration, and invasion, while simultaneously promoting cell apoptosis. CONCLUSIONS: MS4A3 expression is significantly decreased in CC tissues and is significantly correlated with poor prognosis, suggesting that this gene may serve as a potential prognostic biomarker.

MS4A3↗