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PubMed2005

Prognostic and clinical relevance of the World Health Organization schema for the classification of thymic epithelial tumors: a clinicopathologic study of 108 patients and literature review.

STUDY OBJECTIVES: Controversy has ensued about the prognostic relevance of the new World Health Organization (WHO) schema for the classification of thymoma. In this study, we present the clinical and histologic features of 108 thymomas and evaluate the usefulness of this histologic schema in view of the prognosis. DESIGN: Retrospective, clinicopathologic analysis of our experience and a review of recent literature. SETTING: Department of Thoracic and Cardiovascular Surgery of a university hospital. METHODS: A series of 108 thymomas were reviewed and classified by the new WHO schema. The clinical characteristics and the survival outcome were investigated in reference to the WHO subtypes. The Cox proportional hazards model was applied to determine the factors affecting the tumor-related survival. Recent literature on the prognostic relevance of the WHO schema was reviewed. RESULTS: There were 7 type A tumors, 25 type AB tumors, 12 type B1 tumors, 32 type B2 tumors, 20 type B3 tumors, and 12 type C tumors. The histologic subtype closely correlated with the Masaoka stage (p = 0.00). The tumor-related survivals at 5 years and 10 years were 88.0% and 77.9%, respectively. Stage III and IV tumors had a significantly worse prognosis than stage I or II tumors (p < 0.05). Type B3 tumors had an intermediate prognostic ranking in comparison with the carcinomas and with the other groups. On multivariate analysis, the WHO subtype (A-B2 vs B3 vs C) could predict the tumor-related survival, but the Masaoka stage was the most important prognostic factor affecting the postoperative survival (p = 0.026). CONCLUSION: The Masaoka stage is the most important determinant of survival in surgically resected cases of thymoma. To clarify the prognostic relevance and clinical usefulness of the WHO schema, consistent parameters reflecting the surgical outcome and development of the diagnostic tools that could improve the interobserver agreement within type B are needed.

Adult↗

PubMed2005

Prognostic significance of vascular endothelial growth factor, tumor necrosis, and mitotic activity index in malignant pleural mesothelioma.

OBJECTIVES: Tumor growth and metastasis are angiogenesis-dependent events, and several prognostic factors have been determined in malignant mesothelioma. In this study, we investigated the prognostic significance of vascular endothelial growth factor (VEGF), tumor necrosis (TN), and mitotic activity index (MAI) in malignant mesothelioma. For the first time (to our knowledge), we also demonstrated the association between VEGF staining, TN, and MAI in malignant mesothelioma. METHODS: Decortication and VATS materials of 40 patients were investigated. The routinely processed formalin-fixed, paraffin-embedded, hematoxylin-eosin-stained tumor sections that had been used for the original diagnostic purposes were retrieved. Hematoxylin-eosin sections were selected for VEGF immunostaining, TN, and mitotic count. Clinicopathologic data, stage of disease, and survival of patients were all determined. The correlations between variables were evaluated by Spearman rank correlation test. Both univariate analysis using the log-rank test and multivariate analysis using Cox regression model were performed for survival analysis. RESULTS: There was a significant correlation between VEGF staining and TN (r = 0.42, p = 0.006). In univariate analysis, both VEGF staining (p = 0.0002) and TN (p = 0.0055) showed significant correlation with short survival. Also, there was a positive correlation between VEGF and tumor stage (p = 0.046). In multivariate analysis, only VEGF was determined as an independent prognostic factor in malignant mesothelioma (p = 0.001). There was no association between MAI and survival (p = 0.504). CONCLUSIONS: VEGF, known as an important angiogenic peptide, is an independent prognostic factor in malignant pleural mesothelioma. TN stimulates angiogenesis, and we observed a significant correlation between VEGF and TN. However, further studies are needed to evaluate the prognostic significance of angiogenic properties in malignant mesothelioma.

Adult↗

PubMed2006

Severe heart failure at intensive therapy unit--is there an ideal prognostic index?

OBJECTIVE: To assess the applicability of three prognostic indexes--APACHE II, SAPS II and UNICAMP II--in a subgroup of critical heart failure (HF) patients. METHODS: Ninety patients were studied, being 12 females and 78 males. Mean age was 56 (18-83). Patients were ranked in functional class IV (NYHA) or cardiogenic shock secondary to cardiomyopathies: dilated (44%), chagasic (25.5%), ischemic (18%), hypertensive (1.1%), hypertrophic (1.1%), alcoholic (1.1%), and secondary to valvopathies after surgical correction (7.7%). Tables with frequency of categorical variables and descriptive statistics of continuous variables were created in order to describe sample profile for the different variables under study. In order to analyze the relationship between prognostic indexes levels and course towards death, an analysis of the ROC curve, as well as Hosmer and Lemeshow Test of Goodness of Fit calculated, and Standardized Mortality Ratio (SMR) were carried out. RESULTS: The statistical analysis showed low sensitivity, specificity, and accuracy of the three prognostic indexes for HF patients. Mortality was underestimated in this group. Pulmonary thromboembolism (PTE) was a major factor of mortality rate in severe HF. CONCLUSION: The three prognostic indexes under study did not prove to be appropriate for the assessment of cardiopathy patients at Intensive Care Unit (ICU). For HF patients, PTE played a major role in mortality of heart failure. Specific prognostic indexes for cardiopathy patients with severe HF should be proposed, and the discussion on anticoagulation on those patients should be expanded.

Adolescent↗

PubMed2005

Prognostic factors and survival in endocrine tumor patients: comparison between gastrointestinal and pancreatic localization.

Since gastro-entero-pancreatic endocrine tumors are rare and heterogeneous diseases, their prognosis and long-term survival are not well known. This study aimed at identifying prognostic factors and assessing long-term survival in gastro-entero-pancreatic endocrine tumors. A total of 156 patients enrolled. Prognostic factors were determined by univariate/multivariate analysis; survival rates were assessed by the Kaplan-Meier method. The tumors were non-functioning in 59.6% of patients, and originated from the pancreas in 42.9%. At diagnosis, 64.3% of patients had metastases. The tumors were well differentiated in 89.6% of patients. Ki67 was >2% in 39.6% of patients. Primary tumor size was >3 cm in 49.6% of cases studied. For the univariate analysis, the negative prognostic factors were: pancreatic origin (rate ratio 4.64, P = 0.0002), poorly differentiated tumor (rate ratio 7.70, P = 0.0001), primary tumor size >3 cm (rate ratio 4.26, P = 0.0009), presence of distant metastases (liver: rate ratio 5.88, P = 0.01; distant extra-hepatic: rate ratio 13.41, P = 0.0008). The pancreatic site, the poor degree of differentiation and the distant metastases were confirmed as negative prognostic factors at multivariate analysis. Overall 5-year survival rate was 77.5%. Survival rates differed according to: primary tumor site (62% for pancreatic vs 89.9% for gastrointestinal tract, P = 0.0001) and size (65.7% for >3 cm vs 88.8% for < or = 3 cm, P = 0.0003), degree of differentiation (22% for poor vs 86.8% for good, P < 0.0001), Ki67 (53.5% for > 2% vs 90.1% for < or = 2%, P = 0.003), metastases (96.1, 77, 73.3 and 50.1% for absent, local, liver and distant extra-hepatic metastases respectively), age at diagnosis (85.3% for < or = 50 years vs 70.3% for > 50 years, P = 0.03). Although 64.3% of gastro-entero-pancreatic endocrine tumors present metastases at diagnosis, the 5-year survival rate is 77.5%. Pancreatic site, a poor degree of tumor cell differentiation and distant extra-hepatic metastases are the major negative prognostic factors.

Adolescent↗

PubMed2026

PSMB8: an immune-related prognostic marker for low-grade gliomas.

BACKGROUND: Glioma is the most common primary intracranial tumor in adults. As a subunit of immune proteasome, proteasome subunit beta type-8 (PSMB8) may regulate the progression of glioma via participating in degradation and presentation of tumor antigenic peptides, but its prognostic and clinical applicant usage is under investigation. Therefore, this study aimed to comprehensively evaluate the prognostic significance of PSMB8 in low-grade glioma (LGG) and to elucidate its association with the tumor immune microenvironment and potential as a predictor for immunotherapy response. METHODS: Transcriptome data were downloaded from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), Gene Expression Omnibus (GEO) repositories. The correlations between PSMB8 expression and the clinicopathological features of LGG were investigated in our study, and the prognostic role of PSMB8 in LGGs was assessed fully and comprehensively. Furthermore, we evaluated the correlation between PSMB8 expression and LGG immune environment via the experiments and bioinformatic analysis. RESULTS: Our results indicated that, PSMB8 were highly expressed in most tumor tissues, including LGG. Lower expression of PSMB8 was significantly correlated with lower World Health Organization (WHO) grade and isocitrate dehydrogenase (IDH) mutation status. Moreover, PSMB8 showed a promising prognostic ability for LGG patients via nomogram model and receiver operating characteristic (ROC) curves. Association analysis showed that PSMB8 expression was associated with immune cell infiltration in a variety of tumors, including LGG. Our experiments validated the positive correlation between PSMB8 expression and M2-macrophage infiltration level in clinical LGG tissues and invasive ability of LGG cell. CONCLUSIONS: PSMB8 could be used as one of the prognostic indicators of LGG and it could regulate the LGG cell migratory and invasive ability. Besides, PSMB8 is expected to be a promising biomarker of cancer immunotherapy.

Low-grade glioma (LGG)↗

PubMedDate not supplied

[Comparison of prognostic value of high-dose dobutamine stress-echocardiography and exercise testing in patients with idiopathic dilated cardiomyopathy].

INTRODUCTION: It is of the utmost importance to make an accurate assessment of prognosis in patients with idiopathic dilated cardiomyopathy. Both high-dose dobutamine stress-echocardiography and exercise testing have been used for prognostic stratification of these patients. OBJECTIVE: To make head-to-head comparison of high-dose dobutamine stress-echocardiography and exercise testing in prognostic stratification of patients with idiopathic dilated cardiomyopathy. METHODS: A total of 63 consecutive patients (55 men, mean age 50.1 +/- 9.6 years, mean ejection fraction 19.2 +/- 8.4%) with idiopathic dilated cardiomyopathy, left ventricular end-diastolic diameter >60mm, ejection fraction <35%, and adequate echocardiographic window have been studied. Dobutamine stress echocardiography was performed using 5, 10, 20, 30 and 40 mcg/kg/min infusions, in progressive stages lasting 5 minutes each. Wall motion score index and ejection fraction were considered the indices of the left ventricular contractility. Contractile reserve was defined as the difference between the values of these indices obtained at peak dobutamine dose during the test and the baseline values. Exercise testing was performed as supine bicycle ergometry in progressive stages of 25 W lasting 120 seconds each. Patients were followed one year for combined end-point consisting of cardiac death, partial left ventriculectomy and hospitalization for congestive heart failure. RESULTS: Out of 61, 19 (31%) patients met combined end-point during follow-up [cardiac death in 6/61 (10%), partial left ventriculectomy in 4/61 (7%) and hospitalization for heart failure in 9/61 (15%) patients]. Kaplan-Meier survival analysis demonstrated that dobutamine-induced change of wall motion score index was the best parameter for separation of patients in terms of prognosis during the follow-up (log rank=25.34, p<0.001), followed by change of ejection fraction (log rank=16.83, p<0.001) and duration of exercise testing (log rank 13.85, p=0.002). Cox model identified dobutamine-induced change of wall motion score index as the only independent predictor (p<0.001) of combined end-point during one-year follow-up. DISCUSSION: There is a number of studies dealing with the left ventricular contractile indices. These studies are different with respect to studied population, method used to elicit the left ventricular contractile response and the indices of contractile reserve. A number of studies has suggested that the amount of pharmacologically or physically induced change of wall motion score index and ejection fraction can identify patients with dismal prognosis. Peak oxygen consumption is traditionally considered the most accurate prognostic index, but its usefulness has been recently questioned. Our data suggest that high-dose dobutamine stress-echocardiography may be superior to exercise testing for prognostic stratification of patients with idiopathic dilated cardiomyopathy. The reasons for such observation are not clear, but it can be hypothesized that this may be due to multifactorial nature of the exercise tolerance. The most serious potential drawback of methodology is that, because of technical limitations, we did not test peak oxygen consumption in our patients, but since it has been shown that oxygen consumption correlates well with the duration of exercise, we believe that our methodology is valid. CONCLUSION: Both high-dose dobutamine stress-echocardiography and exercise testing can identify patients with dismal prognosis during one-year follow-up, but it appears that dobutamine stress-echocardiography may yield better prognostic significance.

Cardiomyopathy, Dilated↗

PubMedDate not supplied

[New cytogenetic prognostic markers in breast cancer].

BACKGROUND: The aim of this study was to identify chromosomal imbalances in a series of invasive ductal carcinomas. In order to characterize the prognostic value of the chromosomal aberrations, we determined the association between genetic changes, overall survival, recurrences and some well-known prognostic and diagnostic parameters. MATERIAL AND METHODS: We included in this study 70 ductal invasive carcinomas diagnosed at the Hospital of Navarra during 1991-1994. We used the Comparative Genomic Hybridization Technique (CGH) for the molecular cytogenetic analysis of formalin-fixed, paraffin embedded specimens. RESULTS: We obtained successful results in 57 out of 70 cases (81.4%). The most frequent recurring findings were DNA gains on 8q, 17q, 1q, 20q, 11q and 6q and losses on 16q, Xp, Xq, 13q, 11q and 8p. In the survival study, gains on 1q and 11q13 were more frequent in patients with recurrence (41.3% vs. 18.5% and 50% vs. 23.7%). Loss of 16q appears as a prognostic factor of good outcome because of its association with good pathological prognostic features: 100% of tumors with this aberration showed overexpression of Bcl-2, and 75% of them were node negative. Besides, 46.7% of the positive cases for the expression of estrogen receptors also showed this imbalance. CONCLUSIONS: The CGH is a useful technique for the study of paraffin embedded tumors. Our results confirm that the cytogenetic aberrations of tumors could be considered as prognostic factors contributing to a better knowledge of tumor outcome.

English Abstract↗

PubMed2003

Development and application of a scoring system for prognostic evaluation of equine liver biopsies.

REASONS FOR PERFORMING STUDY: The study was designed to investigate the prognostic value of liver biopsy during investigation of cases of suspected liver disease in mature horses. HYPOTHESIS: That liver biopsy is the most prognostically useful technique in common usage in the investigation of suspected liver disease. METHODS: This study examined the prognostic value of liver biopsy during the investigation of suspected liver disease in 73 mature horses. Histopathological variables comprising fibrosis, irreversible cytopathology, inflammatory infiltration, haemosiderin accumulation and biliary hyperplasia were found to be significant predictors of nonsurvival and were used to formulate a weighted biopsy score representing a prognostically useful broad comparative index of histopathological severity. Minimum and maximum possible scores were 0 and 14 points, respectively. RESULTS: Retrospective application of the biopsy scoring system to the study population indicated that horses with scores of 0 or 1 were equally likely to survive to 6 months with a combined mortality of 4%. Horses with biopsy scores between 2 and 6 had a combined mortality of 33% and were at a 12-fold increased risk of nonsurvival within 6 months (hazard ratio = 12.04, 95% CI 134-107.81, P = 0.026) compared to horses with a biopsy score of 0. Horses with biopsy scores between 7 and 14 had a combined mortality of 86% and were at a 46-fold increased risk of nonsurvival (hazard ratio = 46.01, 95% CI 5.92-357.5, P < 0.001) compared to horses with biopsy score 0. CONCLUSIONS: Application of the biopsy scoring system to histopathological findings in liver biopsy specimens was very useful in predicting survival of cases of suspected liver disease. POTENTIAL RELEVANCE: Application of the findings in this study may not be directly applicable to other case populations. However, liver biopsy appears to be the most valuable prognostic technique employed during the investigation of suspected cases of liver disease in mature horses.

Animals↗

PubMed1996

Overview on human breast cancer with focus on prognostic and predictive factors with special attention on the tumour suppressor gene p53.

A long list of potential prognostic markers has been analysed for breast cancer, some of them will be reviewed in this article. The lymph node status is still the best prognostic marker. The lymph node status combined with information on tumour size, receptor- and proliferation status of the tumour should be analysed as standard for all breast cancer patients. Prognostic information for breast cancer patients has also been described for the membrane protein c-erbB2, the protease cathepsin D, plasminogen activators and inhibitors, certain oncogenes and tumour suppressor genes. Some of these factors also give potential additional information on the response to different oncological therapies, and are better denoted predictive factors. In this overview we shortly describe the above mentioned prognostic factors with major focus on the tumour suppressor gene p53 and its prognostic value and potential predictive value.

Apoptosis↗

PubMed1993

Large-cell lymphoma: a study of prognostic factors and assessment of five recently proposed predictive systems.

The main initial and evolutive variables of 133 patients with large-cell lymphoma treated with adriamycin-containing regimens were evaluated for prognostic significance. At the time of analysis, 66 patients had died with the median survival of the series being 48.9 months. Variables associated with poor prognosis in the univariate study were: lymphoma of immunoblastic subtype, advanced Ann Arbor stage, presence of B-symptoms, poor performance status, bulky disease (> or = 10 cm), involvement of two or more extranodal sites, bone marrow infiltration, and high serum LDH levels. In the multivariate analysis, Ann Arbor stage (p < 0.001), bulky disease (p = 0.004), performance status (p = 0.018), and histologic subtype (p = 0.021) retained their prognostic value. After excluding those patients with localized disease (stage I), the Ann Arbor staging system lost prognostic significance in favor of bone marrow infiltration (p = 0.009) and serum LDH (p < 0.001). However, when response to treatment was included in the regression model, it proved to be the most important prognostic factor (p < 0.001), followed by serum LDH (p = 0.004). On the other hand, when the analysis was restricted to complete responders, serum LDH at diagnosis was the only parameter useful to predict survival (p = 0.008). Finally, five recently proposed prognostic classifications were useful to separate different risk-groups of patients when applied to the series.

Aged↗

PubMed1999

Evaluation of the proliferative index as a prognostic factor in diffuse large cell lymphoma: correlation with the International Index.

The reasons for differences in outcome between groups of patients with diffuse large cell lymphoma (DLCL) defined by clinical prognostic factors are largely unknown. Measures of cell proliferation may offer a biological explanation for these differences. This study tested the hypothesis that these survival differences between the groups defined by established prognostic factors were due to the proliferative index. The bromodeoxyuridine labeling index (LI), a measure of the S-phase fraction, was prospectively determined on fresh tumor specimens obtained at initial diagnosis in 80 patients with DLCL seen between 1986-1993 at a single institution. Patients were grouped using prognostic factors that were significant in a univariate analysis as well as the International Index (IPI). The LI in each of these groups was compared to determine whether the differences in outcome between the groups could be explained by differences in the LI. The median LI for all patients was 5.1% (range: 0.1-25%). When the predictive effect of the LI on response and survival was analyzed, the LI did not correlate with complete response or disease-free survival (DFS). There was a trend, however, for patients with a lower LI to have a poorer overall survival (p=0.06). When the patients were analyzed using the International Index (IPI), the mean LI for patients in the low-risk, low-intermediate, high-intermediate and high risk groups was 7.1%, 10.0%, 6.4% and 6.6% respectively (p=0.41). When analyzed separately, there was no significant difference in the LI for any of the patient groups defined by significant prognostic factors. The only difference in the LI was that the median LI in patients with T-cell DLCL was significantly lower than the LI in patients with B-cell DLCL (p=0.001) and these patients had an inferior complete response rate (p=0.001), disease-free survival (p=0.003) and overall survival (p=0.015). In this study, the LI, a measure of lymphoma cell proliferation, was not a significant prognostic factor for response, disease-free survival or overall survival. Furthermore, the LI did not explain the differences in outcome between patient groups defined by the IPI. However, a lower LI seen in patients with T-cell DLCL may account for their poorer response to therapy and inferior survival when compared to patients with B-cell DLCL.

Adolescent↗

PubMed2005

Surgical management of spinal metastases: analysis of prognostic factors during a 10-year experience.

OBJECT: Refinement of surgical techniques, especially anterior approaches, for the management of spinal metastases has improved patient outcomes, despite the fact that a complete analysis of the prognostic factors that would inform patient selection has not been undertaken. The authors sought to identify such prognostic factors for neurological outcome and life expectancy in patients with spinal metastases. METHODS: The authors used Kaplan-Meier techniques, log-rank comparisons, and a multivariate model stratified by tumor type to identify prognostic factors for duration of ability to walk and survival in patients who underwent surgical treatment for spinal metastases during a decade when all current treatment options were available. Preoperatively, 53 (87%) of the 61 patients in the study population suffered neurological symptoms (for example, weakness) and 52 (85%) were ambulatory. Postoperatively, 59 (97%) were ambulatory. Most patients who survived 6 months (81%) remained ambulatory, as did 66% of those alive at 1.6 years. The median postoperative survival was 10 months. The risk factors for loss of ambulation were preoperative loss of ambulatory ability, recurrent or persistent disease after primary radiotherapy of the operative site, a procedure other than corpectomy, and tumor type other than breast cancer. Prognostic factors for reduced survival were surgical intervention extending over two or more spinal segments, recurrent or persistent disease after primary radiotherapy involving the operative site, diagnosis other than breast cancer, and a cervical spinal procedure. CONCLUSIONS: The results of this analysis allowed the authors to create a simple prognostic factor scoring system that can be applied to individual patients. The positive experience derived from this study supports an expanded role for the surgical treatment of metastatic spinal disease.

Adolescent↗

PubMed2006

Building and validating a prognostic index for biomarker studies.

An important aspect of modern cancer research is identifying molecular and genetic markers that predict an individual's risk of recurrence and response to treatment. Increasingly, a large number of biomarkers are included in studies, even though at most a small proportion of them will be prognostic. This article considers the selection and validation of prognostic biomarkers, and proposes a method for building and validating a prognostic index based on potentially many markers. We use simulation to show that our proposed method controls false-positive rate while retaining reasonable power. The prognostic index gets its power from combining prognostic biomarkers. It can be very powerful even when there are few markers that are predictive.

Biomarkers↗

PubMed2002

Prognostic value of the urokinase-type plasminogen activator, and its inhibitors and receptor in breast cancer patients.

Urokinase-type plasminogen activator (uPA), its inhibitors (PAI-1 and PAI-2), and its receptor (uPAR) play a key role in tumor invasion and metastasis. This study was designed to evaluate the prognostic impact of uPA, PAI-1, PAI-2, and uPAR and the combination of these factors in a group of 460 primary breast cancer patients. Concentrations of all 4 components of the uPA system were measured in tumor extracts using enzyme-linked immunosorbent assays (American Diagnostica, Inc, Greenwich, CT). After a median follow-up of 33 months, 18.5% of the patients had relapsed. The Cox proportional hazards model was applied for both univariate and multivariate analyses of disease-free survival (DFS). PAI-1 and PAI-2 were shown to provide independent prognostic information in breast cancer. Patients with either low levels of PAI-1 or high levels of PAI-2 were found to have better DFS (relative risk was 2.08 and 1.78, respectively). The prognostic value could be even further improved by a combination of both inhibitors. Aside from the uPA inhibitors, only nodal status and hormonal receptor status retained independent prognostic value. The other 2 invasion markers, uPA and uPAR, showed no statistically significant impact on DFS. In our patients, who were mostly treated with adjuvant therapy, uPA was not found to be an independent prognostic marker for DFS; this could be a consequence of the predictive value of uPA for response to adjuvant therapy and should be further investigated.

Adult↗

PubMed2006

Sex differences in the predictive power of the molecular prognostic factor HER2/neu in patients with non-small-cell lung cancer.

BACKGROUND: Recent studies imply that HER2/neu is a potential prognostic factor in patients with non-small-cell lung cancer (NSCLC). Whereas considerable evidence indicates sex differences in epidemiologic, hormonal, biologic, and genetic factors in this disease, it has remained unknown whether HER2/neu has a diverse function as a prognostic factor in men and women. PATIENTS AND METHODS: We investigated the association between gene expression levels of HER2/neu in the primary tumors of 90 patients with curable resected NSCLC and survival, especially analyzing whether there is a different potential of this molecular factor in its prognostic impact between men and women. RESULTS: High HER2/neu gene expression levels were found in 62 patients (68.9%), and low HER2/neu gene expression levels were found in 28 patients (31.1%). High HER2/neu messenger RNA expression levels were associated with inferior survival (P = 0.09) compared with lower HER2/neu expression. Survival analysis was then carried out separately for men and women in this group of patients. An HER2/neu gene expression cutoff point was identified that separated women, but not men, into good and poor prognostic groups. CONCLUSION: These findings suggest that HER2/neu as a prognostic factor is strongly sex specific, indicating that it is not useful for men but highly predictive for women.

Adult↗

PubMed1998

Prognostic factors for survival after enucleation for choroidal melanoma.

To evaluate the prognostic value of DNA content-ploidy, agoraphilic nucleolar organizing regions (AgNORs) and proliferating cell nuclear antigen (PCNA) for survival among patients with choroidal melanoma choroidal melanomas managed by enucleation in 55 patients with a follow-up of 5 years were studied. AgNor counts were evaluated by two examiners after sections were specifically processed. Immunohistochemistry was performed to evaluate PCNA expression. Kaplan-Meier estimation of survival curves, the log-rank test, and Cox regression analysis were used to compare survival according to the above mentioned factors. Five years after enucleation 62% of patients had died. Patients with spindle cell type melanomas had the best and those with epithelioid cell type had the worst survival (p=0.004). Patients with small tumors had better survival than those with medium or large tumors (p=0.02). Patients having tumors with aneuploid nuclear DNA content had worse survival than those having tumors with diploid DNA content (p=0.004). A high PCNA level correlated with lower survival rates (p=0.02). Patients having a high AgNor count had a worse survival than those with lower counts (p=0.02). DNA content, PCNA level, and AgNOR count each showed a clinically significant influence on patient survival. However, each of these new evaluated prognostic factors was strongly related to one or both of the classic prognostic factors. It is therefore difficult to separate the effects of the two categories of prognostic factors. Results of the Cox regression analysis suggested that these newer evaluated prognostic factors provided little additional information about patient prognosis.

Adult↗

PubMed1999

Prognostic value of estrogen receptor status can be improved by combined evaluation of p53, Bcl2 and PgR expression: an immunohistochemical study on breast carcinoma with long-term follow-up.

Steroid receptor analysis is the only widely accepted prognostic/predictive marker in breast cancer (BC) treatment. In the present study we evaluated the prognostic role of ER/PgR with p53 and Bcl2, in a series of 277 BC (153 pN1/2, 122 pNO, 2 pNx) with a long-term follow-up (67 months for DFS, 75 months for OS). Our results, besides confirming the usefulness of ER immunohistochemical expression as a prognostic marker, showed that PgR expression alone had a borderline/not significant prognostic value in the whole series (p=0.08 for DFS and p=0.09 for OS), while showed to be prognostic in N+ cases (p=0.02 for DFS and p=0.03 for OS). PgR prognostic value, however, was not independent at the multivariate analysis. By combining ER with PgR, p53 and Bcl2, we showed that ER/p53 and ER/Bcl2 phenotypes had a better discriminant role than ER/PgR phenotype. The ER+/p53+ phenotype was at higher risk of relapse/death as compared with ER+/p53- phenotype. Conversely ER-/p53+ phenotype showed the most unfavourable prognosis. Similar results could be observed concerning ER/Bcl2 phenotypes. Our study showed that the combined evaluation of ER/PgR weakly enhanced the prognostic/predictive power of ER status alone. On the contrary, the combined evaluation of ER/p53 and ER/Bcl2, improved this prognostic/predictive capability and allowed the separation of ER positive and ER negative cases into subgroups with different prognosis.

Breast Neoplasms↗

PubMed2000

Uterine smooth muscle tumors: utility of classification by proliferation, ploidy, and prognostic markers versus traditional histopathology.

CONTEXT: Accurate categorization of uterine smooth muscle neoplasms by light microscopic examination is difficult. Multiple classification schemes have been proposed based on mitotic rate, nuclear atypia, and the presence or absence of necrosis. None of these classification systems has been entirely successful. Multiple ancillary techniques have been tested for their ability to predict behavior of uterine smooth muscle tumors. OBJECTIVE: We assayed 45 smooth muscle neoplasms for a variety of proliferation markers, oncogene protein products, and DNA ploidy level to determine if these markers supplied prognostically useful information over and above that obtained by routine light microscopic assessment. STUDY DESIGN: Forty-five uterine smooth muscle neoplasms were assessed for DNA ploidy; silver-staining nucleolar organizer regions (AgNORs); percent nuclear proliferating cell nuclear antigen (PCNA); expression of p53, Her-2/neu, and MDM-2 protein; mitotic rate; and nuclear grade. These markers were correlated with histologic diagnosis and the occurrence of a clinically adverse event (death, metastasis, or recurrence). RESULTS: Diagnostic category (P <.001), nuclear grade (P <.002), mitotic activity (P <.001), mean AgNORs (P <.001), percent nuclear PCNA (P =.02), and expression of p53 (P =.02) all correlated with clinical outcome. No statistically significant correlation between clinical outcome and the categories MDM-2 expression, Her-2/neu expression, or DNA ploidy was seen. Nuclear grade, p53 expression, mitotic rate, AgNORs, and percent nuclear PCNA correlated with diagnosis. CONCLUSIONS: Diagnostic category, mitotic rate, AgNOR counts, PCNA, and p53 expression dichotomized uterine smooth muscle neoplasms into prognostically favorable and unfavorable groups. Although highly significant, the category AgNORs was no more successful than mitotic rate in dividing uterine smooth muscle neoplasms into prognostically favorable and unfavorable groups. Expression of p53 and percent nuclear PCNA dichotomized uterine smooth muscle neoplasms into prognostic groups, but neither technique reached the level of significance achieved by mitotic rate. Our data indicate that mitotic rate and the classification system of Kempson and Bari are at least as effective as the tested markers in separating uterine smooth muscle neoplasms into prognostic categories.

Aneuploidy↗