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PubMed1994

From Dukes through Jass: pathological prognostic indicators in rectal cancer.

In the recently described Jass staging system for resected adenocarcinoma of the rectum, peritumoral lymphocytic infiltration and tumor growth pattern are introduced as significant indicators of prognosis in conjunction with depth of tumor invasion and lymph node metastasis. The authors of this study have tested the applicability of the Jass system by reviewing 348 resected rectal cancers for 12 pathological variables, including two newly recognized features, namely the Crohn's-like lymphoid reaction and metastatic tumor nodules in pericolic fat. By univariate analysis improved 5-year survival rate was associated with tubular-type adenocarcinoma, low tumor grade, retention of tubule configuration and nuclear polarity, expanding tumor growth pattern, prominent peritumoral lymphocytic infiltration, absence of extramural vein invasion by tumor, all levels of intramural and extramural invasion short of widespread local tumor dissemination, a Crohn's-like lymphoid reaction pattern, and absence of both nodal metastasis and tumor nodules in perirectal fat. By Cox stepwise proportional hazards analysis, depth of tumor invasion, lymph node metastasis, Crohn's-like lymphoid reaction, and extramural venous invasion retained independent prognostic significance. Peritumoral lymphocytic infiltration and tumor growth pattern of the Jass staging system failed to compete successfully with other variables in the proportional hazards model, in part because of their correlation with the model's selected variables. Both intramural and extramural extent of tumor invasion coupled with lymph node metastasis form the cornerstones of rectal cancer staging. However, other factors do refine prognostication. From this study the Crohn's-like lymphoid reaction emerges as a significant new independent indicator of prognosis for survival from rectal cancer. Although the Crohn's-like lymphoid reaction and extramural vein invasion took precedence as staging variables in this study, a complex interrelationship with other parameters was observed.

Adenocarcinoma↗

PubMed1986

Prognostic indices for bladder cancer: an analysis of patients with transitional cell carcinoma of the bladder primarily treated by radical megavoltage X-ray therapy.

A group of 889 patients who completed radical X-ray therapy for transitional cell carcinoma of the bladder during a 12 year period were analysed by a multivariate technique. The patient's age, tumour category, tumour size and haemoglobin level were shown to be independent prognostic covariates. A prognostic index was derived and four prognostic subgroups were identified. The prognostic index could divide patients within each T category into those with good, moderate, fair or poor prognosis. The 5 year actuarial survival rate for patients in the poor prognosis group was 5.8% compared to 69.8% for patients in the good prognosis group. Durable local tumour control after radical radiotherapy was also analysed by a multivariate technique. Tumour category, grade, haemoglobin and urea level were found to be significant covariates. A tumour control index was derived and two groups were identified corresponding to a high probability of lasting local control after radical radiotherapy (47.8% of patients) or a low probability of control (52.2%).

Adult↗

PubMed2005

Claudin-1 is a strong prognostic indicator in stage II colonic cancer: a tissue microarray study.

Tight junction associated proteins are key molecular components governing cellular adhesion, polarity and glandular differentiation. Tight junction proteins also play critical roles in cellular proliferation and neoplastic pathways via their functions as couplers of the extracellular milieu to intracellular signaling pathways and the cytoskeleton. Neoplastic cells frequently exhibit structural and functional deficiencies in the tight junction. The purpose of this study was to determine the pattern of expression and prognostic value of four tight junction associated proteins, claudin-1, claudin-4, occludin and ZO-1 in a cohort of TNM stage II colon cancer using tissue microarray technology. In this study, we retrospectively analyzed, resected and otherwise untreated paraffin embedded specimens from 129 consecutive patients with TNM stage II colonic carcinomas for claudin-1, claudin-4, occludin and ZO-1 protein expression by immunohistochemistry. Seventy-five, 58, 56 and 44% of the tumors exhibited normal to elevated expression levels (+2 and +3 immunopositivity) of claudin-1, claudin-4, occludin and ZO-1 respectively. Low expression levels of claudin-1 and ZO-1 were directly associated with higher tumor grade (P=0.05 and 0.03 respectively). Multivariate analysis indicated that lymphovascular invasion (P=0.01) and low levels of claudin-1 (P=0.0001) expression were independent predictors of recurrence and that reduced claudin-1 expression (P=0.0001) was associated with poor survival. This study is the first to comprehensively examine the expression of several tight junction associated proteins in colonic neoplasms and to correlate their expression with disease progression. Loss of claudin-1 expression proved to be a strong predictor of disease recurrence and poor patient survival in stage II colon cancer.

Adult↗

PubMed1988

A multivariate analysis of pathologic prognostic indicators in large bowel cancer.

A multivariate analysis of the pathologic data of 350 patients with primary colorectal cancer was performed. In addition to conventional parameters such as shape and size of the primary tumor, central node involvement, angioinvasive growth, grade, and stage, new variables such as the immunoreactivity patterns of carcinoembryonic antigen (CEA), CA 19-9, mucin, serotonin, secretory component (SC), and the DNA index were tested for their potential prognostic value. Every variable except CA 19-9, serotonin, and DNA showed significant prognostic information in univariate analysis. However, in the multivariate analysis stage was the predictive factor with the highest hazard ratio, but absence of central node involvement, tumors with diameters between 3.5 cm and 6 cm, exophytic tumor growth, well-differentiated tumors, tumors with CEA immunoreactivity, absence for staining with serotonin, and diploid tumors also were included in the relative risk model. Thus, the aforementioned variables appear to play a role in the establishment of a prognostic index.

Aged↗

PubMed2003

Pituitary tumor transforming gene and fibroblast growth factor-2 expression: potential prognostic indicators in differentiated thyroid cancer.

Differentiated thyroid cancers are the most common endocrine cancers, but there are no reliable molecular markers of prognosis. Pituitary tumor transforming gene (PTTG) plays several potential roles in tumor initiation and progression, including regulating mitosis and stimulating expression of fibroblast growth factor (FGF)-2. Increased expression of PTTG has been demonstrated in follicular thyroid lesions, and expression of this oncogene has been identified as a potential prognostic marker in pituitary adenomas and colon carcinomas. We assessed the expression of PTTG and FGF-2 and its receptor FGF-R-1 in 27 differentiated thyroid cancers, and we compared this with expression in 11 normal thyroids, 25 multinodular goiters, and 13 Graves' disease specimens. We also examined the relationship between gene expression and clinical markers of tumor behavior. PTTG and FGF-2 were overexpressed in thyroid carcinomas (9.5-fold increase, P = 0.003, and 5.0-fold increase, P < 0.001, respectively) compared with normal thyroid. Increased FGF-2 mRNA expression was independently associated with the findings of lymph node invasion (R(2) = 0.71; P < 0.001) and distant metastasis (R(2) = 0.55; P = 0.009) at tumor presentation, after taking into account known prognostic factors such as age and gender of the patient and size and type of the tumor. High PTTG expression was independently associated with tumor recurrence (R(2) = 0.64; P = 0.003). We conclude that PTTG and FGF-2 expression are potential prognostic markers (and perhaps therapeutic targets) for differentiated thyroid cancer.

Adult↗

PubMed2006

Quantitative prognostic indices in peritoneal carcinomatosis.

Five different descriptions quantitating peritoneal carcinomatosis are available: the Lyon staging system, the Peritoneal Cancer Index (PCI), the Japanese Research Society for Gastric Cancer carcinomatosis staging (JRSGS), the Dutch simplified peritoneal carcinomatosis assessment and the Completeness of Cytoreduction Score (CCR). These five staging systems are described and discussed. Combinations of these to achieve a complete description of peritoneal lesions prior to and following treatment assist in a correct prognostic assessment for these patients and in a selection of treatment options.

Humans↗

PubMed1997

[The prognostic indices in congenital diaphragmatic hernia. Its management].

The reported mortality for prenatally detected congenital diaphragmatic hernia is high. We retrospectively reviewed 18 cases of congenital diaphragmatic hernia diagnosed prenatally in our hospital and analyzed several high-risk factors adversely affecting outcome. The diagnosis before 32 weeks gestation is associated with high mortality than in cases detected later. Polyhydramnios and underdevelopment of left-side cardiac structures were found to be helpful prognostic factors. These should be taken into account when the management of these cases is planed.

Bulgaria↗

PubMed1997

Canine monocytic ehrlichiosis: a retrospective study of 100 cases, and an epidemiological investigation of prognostic indicators for the disease.

One hundred cases of monocytic ehrlichiosis diagnosed in Israeli dogs were confirmed by the presence of anti-Ehrlichia canis indirect immunofluorescent antibody titres greater than 1:40. The disease occurred in all age groups and there was no sex predilection. German shepherd dogs were significantly over-represented whereas crossbreed dogs were significantly under-represented (P > 0.0005). The most common clinical signs were depression, lethargy, lymphadenomegaly, fever, anorexia, panting, pale mucous membranes and bleeding, of which epistaxis was most common. Thrombocytopenia, anaemia (mainly normocytic normochromic) and lymphopenia were the predominant haematological findings. Forty-nine of the 100 cases were followed up for a year. Thirty-two dogs survived and 17 died. A Cox proportional hazards regression model was used to examine the effect of host, environmental, and haematological prognostic factors on survival. It was concluded that severe anaemia, severe leucopenia, pancytopenia, a tendency to bleed (especially epistaxis) and being a German shepherd dog were important indicators of poor survival in cases of monocytic ehrlichiosis in dogs.

Animals↗

PubMed2004

WHO histologic classification is a prognostic indicator in thymoma.

BACKGROUND: The histologic classification of thymoma has remained a subject of controversy for many years. In 1999, the World Health Organization Consensus Committee published a histologic typing system for tumors of the thymus. METHODS: We reclassified a series of 100 thymomas resected at Tokushima University Hospital and four affiliated hospitals in Japan between 1973 and 2001 according to the World Health Organization histologic classification and reported its clinicopathologic relationship and prognostic relevance. RESULTS: There were 8 type A, 17 type AB, 27 type B1, 8 type B2, 12 type B3, and 28 type C thymomas. The frequency of invasion to neighboring organs increased according to tumor subtype in the order A (0%), AB (6%), B1 (19%), B2 (25%), B3 (42%), and C (89%). There was no recurrence in patients with type A, AB, or B2 thymoma. The recurrence rates of patients with B1, B3, or C thymoma were 15%, 36%, and 47%, respectively. The disease-free survival rates were 100% for types A and AB, 83% for types B1 and B2, 36% for type B3, and 28% for type C thymoma at 10 years. There were significant differences in disease-free survival between types A and AB and types B1 and B2 (p = 0.0436), and between type B3 and type C (p = 0.042). By multivariate analysis, only Masaoka clinical stage (p = 0.002) showed significant independent effects on disease-free survival. The 10-year survival rates of types A and AB, types B1 and B2, type B3, and type C thymoma were 100%, 94%, 92%, and 58%, respectively. CONCLUSIONS: The current study confirmed the World Health Organization histologic classification as a good prognostic factor.

Adolescent↗

PubMedDate not supplied

Gelatinases (MMP-2 and -9) and their natural inhibitors as prognostic indicators in solid cancers.

Neoplastic growth and dissemination involve increased proteolytic activity that is able to escape the regulative elements. Matrix metalloproteinases (MMPs), particularly gelatinases A and B (MMP-2 and -9), play a role in tumor invasion and angiogenesis, and they participate in cancer progression in several neoplasias. The expression of tissue inhibitors of gelatinases, TIMPs-1 and -2, has also been shown to be associated with the clinical course in some cancers. The prognostic value of these markers, however, seems to vary a great deal in different neoplastic diseases. In this review, the impact of the gelatinases and their inhibitors on the clinical course in several solid cancers is evaluated based on the growing data from recent clinical studies. The clinical data most often explore the overexpression of mRNA or immunoreactive protein in tumor tissue, or measure the concentration of the circulating proteinase or its inhibitor in pretreatment or follow-up serum samples. The growing amount of recent clinical data suggests that the impact of gelatinases on treatment decisions should be tested in clinical trials.

Clinical Trials as Topic↗

PubMed2001

Malignant peripheral nerve sheath tumours: high Ki67 labelling index is the significant prognostic indicator.

AIMS: We investigated p53, Ki67, MDM2, and p21WAF1/CIP1 in order to evaluate its relationship with prognosis in malignant peripheral nerve sheath tumours (MPNST). METHODS AND RESULTS: In 49 cases of MPNSTs, the immunohistochemical studies of Ki67, p53, MDM2, p21WAF1/CIP1 and polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) with direct sequencing of p53 were performed with the formalin-fixed paraffin-embedded tissue. In 43 cases with survival data available, an evaluation of the prognostic significance of clinicopathological factors was also carried out. A high Ki67 labelling index (LI) (>25%) was correlated with a reduced survival rate in the 43 cases of MPNST (P=0.0106, log-rank test). Furthermore, there was a significant correlation between the Ki67 LI and the immunohistochemical expression of p53 or MDM2. In 17 MPNST cases, PCR amplification of exons 5 through 8 of the p53 gene was successful. One case showed a base change of codon 240 (AGT-->AGC), but translated amino acid (Ser) remained unchanged. Multivariate Cox analysis of our series showed that the association of von Recklinghausen's disease, tumour depth, and the presence of rhabdomyoblasts (malignant triton tumour) each had an independent negative impact on overall survival. CONCLUSION: High Ki67 LI (>25%) was of significant prognostic value in MPNST.

Adolescent↗

PubMed1979

Carcinoembryonic antigen in breast-cancer tissue: a useful prognostic indicator.

Sections of breast carcinomas removed from 69 patients six to 13 years previously were examined using an immunoperoxidase technique to determine whether carcinoembryonic antigen (CEA) was present. Patients who had CEA-negative tumours had significantly higher five- and 10-year survival rates. The difference was not related to the stage of the disease, postoperative treatment, or histological type of tumour. These results suggest that immunohistological assessment of CEA in breast-cancer tissue may provide more precise prognostic information.

Adult↗

PubMed2006

Perinuclear leucine-rich repeats and immunoglobulin-like domain proteins (LRIG1-3) as prognostic indicators in astrocytic tumors.

We have previously characterized three human leucine-rich repeats and immunoglobulin-like domains (LRIG) genes and proteins, named LRIG1-3 and proposed that they may act as suppressors of tumor growth. The LRIG1 transmembrane protein antagonizes the activity of epidermal growth factor receptor family receptor tyrosine kinases. In this study, we evaluated the mRNA expression level of LRIG1-3 in human glioma cell lines and control-matched glioma tissues, characterized the sub-cellular localization of an LRIG3-GFP fusion protein, and analyzed the relationship between sub-cellular localization of LRIG1-3 and clinical parameters in 404 astrocytic tumors by immunohistochemistry. LRIG1-3 mRNA was detected in all human glioma cell lines and matched glioma samples, with large differences in the expression levels. Ectopically expressed LRIG3-GFP localized to perinuclear and cytoplasmic compartments, and to the cell surface of transfected glioma cells. Perinuclear staining of LRIG1-3 was associated with low WHO grade and better survival of the patients. Perinuclear staining of LRIG3 was associated with a lower proliferation index and was in addition to tumor grade, an independent prognostic factor. Furthermore, within the groups of grade III and grade IV tumors, perinuclear staining of LRIG3 significantly correlated with better survival. These results indicate that expression and sub-cellular localization of LRIG1-3 might be of importance in the pathogenesis and prognosis of astrocytic tumors.

Adolescent↗

PubMed2006

Serum albumin as a prognostic indicator for HIV disease progression.

Low albumin levels have been associated with HIV progression. The objective of this analysis was to confirm this association and to further examine the effect of albumin before and after HIV seroconversion on disease progression. The association was first examined among individuals already infected with HIV at entry into a community-based cohort (n = 453) and further assessed among HIV seroconverters with albumin concentrations measured after (n = 219) and before seroconversion (n = 138). The prognostic effect of albumin on AIDS, AIDS mortality, and all-cause mortality was examined using Cox regression. Among 453 HIV-infected individuals, albumin <35 g/liter was associated with faster progression to AIDS [adjusted relative hazard (ARH), 1.8; 95% confidence interval (CI), 1.2-2.8], AIDS mortality (ARH, 2.2; 95% CI, 1.3-3.8), and all-cause mortality (ARH, 2.4; 95% CI, 1.6-3.5). Analyses restricted to HIV seroconverters were similar. Preseroconversion levels of albumin did not predict outcomes, but HIV seroconversion appeared to lower albumin levels. These data show that albumin <35 g/liter after HIV seroconversion is associated with faster HIV disease progression and suggest that low albumin levels are probably a consequence of HIV infection rather than merely reflective of some individuals inherently having low albumin levels.

Adolescent↗

PubMed2004

High-dose therapy and autologous hematopoietic stem-cell transplantation for recurrent or refractory pediatric Hodgkin's disease: results and prognostic indices.

PURPOSE: To evaluate the outcome of pediatric patients with refractory or relapsed Hodgkin's disease (HD) who undergo high-dose therapy and autologous hematopoietic stem-cell transplantation (AHSCT). PATIENTS AND METHODS: From 1989 to 2001, 41 pediatric patients with relapsed or primary refractory HD underwent high-dose therapy followed by AHSCT according to one of four autologous transplantation protocols at Stanford University Medical Center (Stanford, CA). Pretreatment factors were analyzed by univariate and multivariate analysis for prognostic significance for 5-year overall survival (OS), event-free survival (EFS), and progression-free survival (PFS). RESULTS: At a median follow-up of 4.2 years (range, 0.7 to 11.9 years), the 5-year OS, EFS, and PFS rates were 68%, 53%, and 63%, respectively. Multivariate analysis determined the following three factors to be significant predictors of poor OS and EFS: extranodal disease at first relapse, presence of mediastinal mass at time of AHSCT, and primary induction failure. Two of these factors also predicted for poor PFS (extranodal disease at time of first relapse and presence of mediastinal mass at time of transplantation). CONCLUSION: More than half of children with relapsed or refractory HD can be successfully treated with the combination of high-dose therapy and AHSCT, confirming the efficacy of this approach. Further investigation is now required to determine the optimal timing of AHSCT, as well as to develop alternative regimens for those patients with factors prognostic for poor outcome after AHSCT.

Adolescent↗

PubMed2003

DNA methylation patterns in cancer: novel prognostic indicators?

DNA methylation is an epigenetic phenomenon influencing the normal function of DNA and its scaffolding proteins. Especially in cancer, aberrant methylation patterns may contribute to the disease process by the induction of point mutations, activation of inactive genes through hypomethylation of promoters, and transcriptional inactivation through a complex interplay with histone acetylation and other inhibitory mechanisms. Aberrant methylation patterns have been evaluated as tools in the management of patients with cancer. The predictive value, the therapeutic manipulation and the prognostic significance of aberrantly methylated gene loci have been tested in hematological as well as in solid neoplasias in adults and children. A seemingly insurmountable wealth of data has been generated, however, data on clinical associations are sometimes presented in an almost incautious fashion. Nevertheless, some genes like p15INK4B in myelodysplastic syndrome (MDS) and p16INK4A in some lung cancer subtypes have been shown to confer a certain prognosis. In selected cases the data have been confirmed by independent studies. Assays have been developed that can be used by almost any clinical laboratory (e.g. methylation-specific PCR) for the rapid and affordable screening of tumors for aberrant methylation. The study of aberrant methylation patterns has successfully entered the arena of relevant clinical applications. Importantly, methylation does not only hold the potential for being 'just another' biomarker, but also, as it can be reverted chemically, it is a phenomenon that holds great promise for therapeutic exploitation.

Animals↗

PubMed1984

A comparison of the Norris and Killip coronary prognostic indices.

Of the two most frequently used indices for classifying prognosis of patients with an acute myocardial infarction, the Killip index, because of its greater simplicity, is sometimes used instead of the more complicated and time consuming Norris index. The purpose of the current research was to correlate the classification of patients on the two indexes, and to determine reasons for disagreements in classification. Study patients for this comparison included 151 patients who died of a myocardial infarction and who were matched to each of 151 survivors for age, sex, race, and date hospitalization. Pertinent data were extracted from each patient's medical record by specially trained research technicians. The results indicate that many patients were "misclassified": 40% of the deaths were placed in the two lowest severity classes using the Killip scale, and 12% using the Norris index. Good agreement was found for comparisons between the 4-category Killip scale and the continuous scale Norris index ( Jaspen 's multiserial r = 0.67), but only fair agreement was noted when the Norris index was arranged into ordinal categories. Deficiencies in the Killip index included absence of crucial clinical features with prognostic power (e.g., age, systolic blood pressure, infarct location), while the Norris index was deficient in its requirement for a chest radiograph to estimate the presence of pulmonary edema and of cardiac enlargement. If future prospective studies confirm our analysis, research findings which have been based on one or the other of these indices should not be interpreted similarly.

Epidemiologic Methods↗

PubMed1998

Contrast-enhanced MR imaging as a prognostic indicator of breast cancer.

BACKGROUND: Using contrast-enhanced MR imaging in the diagnosis of breast cancer may provide additional information not only on tumor extension but also on the biological behavior of tumors. Thus certain characteristics such as tumor angiogenesis and the proliferating activity of the tumor, which have been shown to correlate significantly with prognosis, are both potentially amenable to analysis by MR imaging. MATERIAL AND METHODS: We compared contrast enhancement in 50 malignant breast tumors at MR imaging to several prognostic factors, such as tumor size, lymph-node status, histological grade of malignancy, tumor angiogenesis, and proliferating activity as shown by the mitotic count and PCNA immunoreactivity. RESULTS: There was significant correlation between contrast enhancement at MR imaging of breast cancer and both tumor angiogenesis and proliferative cellular activity as shown by PCNA immunoreactivity. Furthermore, there was a correlation between contrast enhancement and tumor malignancy grade as well as tumor invasiveness. CONCLUSION: These observations suggest that contrast enhancement at MR imaging may be influenced by factors that have prognostic value. If this assumption is correct, contrast-enhanced MR imaging may become a valuable prognostic tool in the pre-operative evaluation of breast cancers.

Breast Neoplasms↗