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Vascular integrin alpha(v)beta3: a new prognostic indicator in breast cancer.

Blood vessel density is a prognostic indicator of multiple tumor types. Recently, it has been established that tumor-associated blood vessels express elevated levels of integrin alpha(v)beta3. In fact, there is evidence that integrin alpha(v)beta3 identifies the most proliferative endothelial cells within human breast carcinomas. Therefore, we evaluated breast cancer tissue in terms of both blood vessel density and alpha(v)beta3 expression. We found that the antibody LM609 to integrin alpha(v)beta3 preferentially stains the blood vessels of small caliber. Furthermore, comparative studies between LM609 and anti-CD31 antibodies on normal breast indicate that very low and weak expression of integrin alpha(v)beta3 was found on vessels within normal tissue, whereas CD31 antigen was expressed in almost all vasculature. Indeed, expression of integrin alpha(v)beta3 was significantly higher in tumors of patients with metastasis than in those without metastasis. In a series of 197 consecutive patients with invasive breast cancer and long follow-up, vascular expression of integrin alpha(v)beta3 in tumor vascular "hot spots" was found to be the most significant prognostic factor predictive of relapse-free survival in both node-negative and node-positive patients. These findings support the contention that angiogenesis plays a critical role in breast cancer progression and suggest that integrin alpha(v)beta3 is an endothelial cell marker with significant prognostic value and potential usefulness as a target for specific antiangiogenic therapy.

Adult↗

Mammographic casting-type calcification associated with small screen-detected invasive breast cancers: is this a reliable prognostic indicator?

AIM: The aim of the present study was to establish whether mammographic casting-type calcification associated with small screen-detected invasive breast cancers is a reliable prognostic indicator. METHODS AND MATERIALS: We retrospectively identified 50 consecutive women diagnosed with an invasive cancer less than 15 mm who showed associated casting calcification on their screening mammograms. Controls were identified that showed no microcalcification and were matched for tumour size, histological type and lymph node status. A minimum of 5 years follow-up was obtained, noting recurrence and outcome. Conditional and unconditional logistic regression, depending on the outcome variable, were used to analyse the data, taking the matched design into account in both cases. Where small numbers prohibited the use of logistic regression, Fisher's exact test was used. RESULTS: Five deaths from breast cancer occurred out of the 50 cases, of which three were lymph node positive, two were lymph node negative and none were grade 3. None of the 78 control cases died from breast cancer. The difference in breast cancer death rates was significant by Fisher's exact test (p=0.02). Risk of recurrence was also significantly increased in the casting cases (OR=3.55, 95% CI 1.02-12.33, p=0.046). CONCLUSION: Although the overall outcome for small screen-detected breast cancers is good, our study suggests that casting calcification is a poorer prognostic factor. The advantage of a mammographic feature as an independent prognostic indicator lies in early identification of high-risk patients, allowing optimization of management.

Breast Neoplasms↗

Bone marrow eosinophilia as a prognostic indicator in acute myelogenous leukemia with 8;21 translocation.

The pretreatment characteristics of nine acute myelogenous leukemia (AML) patients with 8;21 translocation were evaluated to assess their value as prognostic indicators. All patients had AML-M2 according to French-American-British classification. The percentage of eosinophils in the bone marrow (EO/BM) correlated negatively with the percentage of blast cells in the peripheral blood (BL/PB) (p less than 0.05) and positively with complete remission duration (p less than 0.01). Three of the six patients with EO/BM under 5% showed aggressive clinical courses complicated with extra marrow lesions, while the patient with the highest EO/BM was the only one who survived for 5 years. These findings suggest that bone marrow eosinophilia could be useful as a prognostic indicator in AML patients with t(8;21).

Adult↗

The role of serum uric acid as a prognostic indicator of the severity of maternal and fetal complications in hypertensive pregnancies.

OBJECTIVE: To examine whether an elevated serum uric acid level in hypertensive pregnant women is a useful prognostic indicator of severe hypertension; hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome; and small for gestational age (SGA) infants. METHODS: A total of 459 women newly diagnosed with hypertension in pregnancy were categorized into "gestational hypertension" and "hypertension with proteinuria (preeclampsia)" groups. Their serum uric acid levels were correlated with the development of HELLP syndrome, severity of hypertension, and incidence of SGA newborns (< 10th percentile birth weight). HELLP syndrome was divided into 3 classes depending on the severity of the thrombocytopenia. Prior to this study, serum uric acid levels had been measured in a group of normotensive women. Mean and standard deviation of serum uric acid levels for each group were compared using analysis of variance and student t-tests, where necessary. RESULTS: Significant elevation in serum uric acid levels over normotensive pregnant women (285 +/- 72 micromol/L) was observed in both the gestational hypertensive group (341 +/- 83 micromol/L) and the preeclamptic group (384 +/- 93 micromol/L) of women (p < 0.001 and p < 0.05 respectively). Serum uric acid levels were also significantly elevated (p < 0.001) in women with gestational hypertension with HELLP syndrome (382 +/- 78 micromol/L) compared to those without HELLP syndrome (330 +/- 80 micromol/L). Preeclamptic women with HELLP syndrome (412 +/- 99 micromol/L) also demonstrated elevated uric acid levels (p < 0.05) over those without HELLP syndrome (374 +/- 87 micromol/L). However, the level of uric acid did not predict the severity of HELLP syndrome. The presence of SGA infants in the gestational hypertensive group was not associated with increased uric acid levels. CONCLUSION: Uric acid levels, although significantly elevated in women with gestational hypertension and preeclampsia as compared to normotensive pregnant women, are not good prognostic indicators of the severity of the maternal or fetal complications.

Biomarkers↗

The value of 6-phosphogluconate dehydrogenase (6-PGDH) activity as a marker of tumour cellularity and prognostic indicator in primary breast cancer.

The value of 6-phosphogluconate dehydrogenase (6-PGDH) activity as a cytosolic marker of tumour cellularity has been assessed, together with its use as a prognostic indicator for primary breast cancer in 87 patients over 4 years. 6-PGDH activity shows a good correlation with histologically-assessed tumour cellularity in a sample of 114 patients (correlation coefficient = 0.83). Patients whose primary breast tumour had a high 6-PGDH activity showed poor relapse-free survival times when compared to those with low 6-PGDH activities (Log Rank chi 2 = 6.87, P less than 0.01). This compared with a Log Rank chi 2 of 2.22, P less than 0.20 for oestrogen positive and negative patients. These results suggest that 6-PGDH activity is a better prognostic indicator in primary breast cancer than oestrogen receptor status.

Breast Neoplasms↗

Bioelectrical impedance phase angle as a prognostic indicator in advanced pancreatic cancer.

Bioelectrical impedance analysis (BIA) is an easy-to-use, non-invasive and reproducible technique to evaluate changes in body composition and nutritional status. Phase angle, determined by BIA, has been found to be a prognostic indicator in several chronic conditions, such as HIV, liver cirrhosis, chronic obstructive pulmonary disease and lung cancer, and in patients undergoing dialysis. The present study investigated the prognostic role of phase angle in advanced pancreatic cancer. We evaluated a case series of fifty-eight stage IV pancreatic cancer patients treated at Cancer Treatment Centers of America at Midwestern Regional Medical Center (Zion, IL, USA) between January 2000 and July 2003. BIA was conducted on all patients using a bioelectrical impedance analyser that operated at 50 kHz. The phase angle was calculated as capacitance (Xc)/resistance (R) and expressed in degrees. The Kaplan-Meier method was used to calculate survival. Cox proportional hazard models were constructed to evaluate the prognostic effect of phase angle independent of other clinical and nutritional variables. The correlations between phase angle and traditional nutritional measures were evaluated using Pearson and Spearman coefficients. Patients with phase angle <5.0 degrees had a median survival time of 6.3 (95% CI 3.5, 9.2) months (n 29), while those with phase angle >5.0 degrees had a median survival time of 10.2 (95% CI 9.6, 10.8) months (n 29); this difference was statistically significant (P=0.02). The present study demonstrates that phase angle is a strong prognostic indicator in advanced pancreatic cancer. Similar studies in other cancer settings with larger sample sizes are needed to further validate the prognostic significance of the phase angle.

Adult↗

The prognosis and main prognostic indicators of Guillain-Barré syndrome. A multicentre prospective study of 297 patients. The Italian Guillain-Barré Study Group.

To assess the prognosis of the Guillain-Barré syndrome and identify the main prognostic indicators, 297 patients with Guillain-Barré syndrome recruited through a network of Italian centres were followed up for 24 months or until clinical recovery, whichever was earliest. For each patient the time to plateau, improvement, clinical recovery, or death was calculated, and prognostic indicators (age, sex, antecedent events, disability at admission and nadir, electrophysiological patterns) and treatments were noted. The mean duration of follow-up was 309 days. During this period, 212 patients (71%) recovered, 48 (16%) had residua and 33 (11%) died. The mean times to nadir, improvement and clinical recovery were 12, 28 and 200 days. Using life-tables and survival curves, the cumulative probability of achieving the plateau of symptoms was 73% by 1 week and 98% by 4 weeks. Improvement started during the first week in 36% of cases and within 4 weeks in 85%. The rates of clinical recovery at 1 and 4 weeks, 6, 12 and 24 months were 4, 24, 57, 70 and 82%, respectively. The chance of recovery was significantly affected by age, antecedent gastroenteritis, disability, electrophysiological signs of axonopathy, latency to nadir and duration of active disease. The main treatments did not seem to affect the chance of recovery.

Adolescent↗

Significance of macroscopic tumor necrosis as a prognostic indicator for renal cell carcinoma.

PURPOSE: We investigated the prognostic significance of macroscopic tumor necrosis in renal cell carcinoma. MATERIALS AND METHODS: We retrospectively analyzed the records of 485 patients who underwent surgical treatment for organ confined or metastatic renal cell carcinoma. The presence or absence of tumor necrosis was evaluated based on macroscopic description of the tumor, and tumors were considered necrotic only if they exhibited more than 10% macroscopic necrosis. RESULTS: Macroscopic tumor necrosis was identified in 27% of total patients. Patients with macroscopic necrotic renal cell carcinoma were more likely to have larger tumor, metastatic disease, higher local stage and higher tumor grade (all p < 0.001). Pathological features of microvascular invasion (p = 0.026) and sarcomatoid differentiation (p = 0.002) along with several laboratory findings were also observed to be associated with macroscopic tumor necrosis. Among the total subjects those without macroscopic tumor necrosis had significantly higher progression-free (p < 0.0001) and disease specific survival (p < 0.0001). When survival analysis was limited to nonmetastatic tumors only, the same logic applied, which was not the case for the patients with metastatic disease (p > 0.05). Among the different histological subtypes of renal cell carcinoma, macroscopic tumor necrosis was observed to have a significant impact only for the clear cell subtype. In patients with nonmetastatic RCC multivariate analysis revealed that macroscopic tumor necrosis (p = 0.004) was an independent prognostic predictor of disease specific survival along with pathological T stage, tumor grade and tumor size. CONCLUSIONS: Our results suggest that macroscopic tumor necrosis may be a reliable prognostic indicator for nonmetastatic clear cell renal cell carcinoma which should routinely be examined for during pathological analysis.

Adult↗

Submersion in The Netherlands: prognostic indicators and results of resuscitation.

STUDY OBJECTIVES: To analyze prognostic indicators and the outcome of resuscitation in submersion victims (drowning and near drowning). DESIGN: Retrospective study. SETTING: Intensive and Respiratory Care Unit. Between January 1, 1979, and December 31, 1985, 87 submersion victims were admitted. The files of 83 victims were available for statistical analysis. There were 66 male victims and 17 female victims; the average age was 31.4 +/- 25.8 years. There were ten salt water and 73 fresh water submersions. MEASUREMENTS AND MAIN RESULTS: Predictors for better survival potentials were a young age, submersion of less than ten minutes, no signs of aspiration, and a central body temperature of less than 35 C at admission. We did not detect factors that accelerated a decrease in core body temperature at admission and assume that lethal hypoxia had preceded protective hypothermia in our submersion victims. The Orlowski score had a predictive value but at the same time we found nonindependent indicators in this score. Neurologic outcome in our patients, who were not treated according to a brain protection protocol, was not worse than the outcome published by authors who have used such a protocol. Thirty-three percent of the victims with a cardioventilatory arrest (15) and all victims with a ventilatory arrest (11) survived resuscitation and were discharged. Five nonarrest victims died due to late complications. CONCLUSION: This study shows that no indicator at the rescue site and in the hospital is absolutely reliable with respect to death or survival.

Adolescent↗

C-reactive protein is a prognostic indicator in patients with perihilar cholangiocarcinoma.

AIM: To evaluate prognostic indicators for the outcome of patients with perihilar extrahepatic cholangiocarcinoma in an unselected cohort. METHODS: We retrospectively analyzed 98 patients with perihilar cholangiocarcinoma. Twenty-three patients (23.5%) underwent tumor resection. Patients with non-resectable tumors underwent either transpapillary or percutaneous transhepatic biliary drainage. Additionally, 32 patients (32.7%) received photodynamic therapy (PDT) and 18 patients (18.4%) systemic chemotherapy. Predefined variables at the time of diagnosis and characteristics considering the mode of treatment were entered into a Cox's proportional hazards model. Included in the analysis were age, tumor stage following the modified Bismuth-Corlette classification, bilirubin, prothrombin time (PT), C-reactive protein (CRP), carbohydrate antigen 19-9 (CA19-9), history of weight loss, surgical resection, chemotherapy and PDT. RESULTS: The Kaplan-Meier estimate of overall median survival was 10.5 (95%CI: 8.4-12.6) mo. In the univariate analysis, low Bismuth stage, low CRP and surgical resection correlated significantly with better survival. In the multivariate analysis, only CRP (P = 0.005) and surgical resection (P = 0.029) were found to be independently predictive of survival in the cohort. Receiver operating characteristic (ROC) analysis identified a CRP level of 11.75 mg/L as the value associated with the highest sensitivity and specificity predicting a survival > 5 mo. Applying Kaplan-Meier analysis, patients with a CRP < 12 mg/L at the time of diagnosis had a significantly longer median survival than patients with higher values (16.2 vs 7.6 mo; P = 0.009). CONCLUSION: This retrospective analysis identified CRP level at the time of diagnosis as a novel indicator for the prognosis of patients with perihilar cholangiocarcinoma. It should be evaluated in future prospective trials on this entity.

Adult↗

Prognostic indicators for in vitro fertilization success.

To examine possible prognostic indicators for success and multiple pregnancy in a free-standing in vitro fertilization program, a chart review study based on 160 oocyte retrievals was undertaken. Evaluated factors included the woman's age, diagnosis, baseline follicle-stimulating hormone levels, peak estradiol levels, estradiol patterns, cycle day of oocyte retrieval, oocyte quality, and number of embryos transferred. Factors associated with a higher pregnancy rate and a higher multiple pregnancy rate may include age less than or equal to 35; diagnosis of unexplained infertility; pattern A early estradiol response; oocyte retrieval on cycle day 16; 2 or fewer fractured oocytes at retrieval; and transfer of 4 or more embryos.

Adult↗

Evaluation of a displacement assay with tamoxifen as prognostic indicator in breast-cancer patients with estrogen-receptor-positive tumors.

A displacement assay with tamoxifen, based on the relative binding affinity of tamoxifen and estradiol for the estrogen receptor (ER), was proposed in 1990 as prognostic indicator for breast-cancer patients. Validation of its predictive results in relation to the outcome of 73 patients with ER+ tumors is analyzed. ER, progesterone receptor (PgR) determinations and other conventional prognostic factors in relation to the displacement assay, were considered. Displacement assay results allowed ER+ tumors to be grouped as displaceable (D) or weakly displaceable (WD), with the implication that D tumors should respond better to tamoxifen (Tam) administration. Survival and disease-free interval curves showed highly significant differences between patients with ER+ D and ER+ WD tumors. For survival, including all tumor stages, 73.9% of patients were alive at 9 years after surgery in the group with D tumors and 37.0% in the group with WD tumors (p < 0.005); relative contribution of the different stages is analyzed. Addition of axillary-node number increased the prognostic significance of displacement categories for survival and disease-free interval. PgR determination as another ER functional expression failed to show significant differences for survival and disease-free interval between ER+ PgR+ and ER+ PgR- tumors. Thus, results from the displacement assay and from PgR determinations reflect 2 independent ER functional expressions. Displacement assay data appear as reliable prognostic indicators of breast-cancer outcome, and contribute to more appropriate treatment decisions in this pathology.

Antineoplastic Agents, Hormonal↗

Peritoneal cancer index: a prognostic indicator of survival in advanced ovarian cancer.

AIM: The peritoneal cancer index (PCI) has been used for the detailed evaluation of the peritoneal spread in tumors of gastrointestinal origin and has been found to be a prognostic indicator of survival. The aim of this study was the identification of the significance of the peritoneal cancer index in advanced ovarian cancer. METHODS: From 1990 to 2001, 60 women, mean age 65+/-10.84 (41-86), were treated for advanced ovarian cancer. The performance status (Karnofsky performance scale), age, prior surgery score (PSS), peritoneal cancer index (PCI), tumor volume, tumor grade, residual tumor, the presence of ascites, treatment with adjuvant chemotherapy, histopathologic subtype and FIGO stage were retrospectively correlated to survival using univariate model of statistical analysis. RESULTS: Hospital mortality and morbidity were 11.7 and 16.7% respectively. The recurrence rate was 23.3%. Overall 5-year survival rate was 41% and mean survival 63+/-8 months. The peritoneal cancer index was related to survival (P=0.0253). The other favorable clinical prognostic indicators of survival were low grade and small volume tumors, treatment with adjuvant chemotherapy and complete cytoreductive surgery (P<0.05). CONCLUSIONS: The peritoneal spread in advanced ovarian cancer can be assessed in detail using the peritoneal cancer index. It is a significant prognostic factor of survival and is useful in identifying subgroups.

Adult↗

Beta-microseminoprotein immunoreactivity as a new prognostic indicator of prostatic carcinoma.

Human beta-microseminoprotein (beta-MSP), isolated from seminal plasma, is one of the proteins secreted by the prostate gland. To determine whether the beta-MSP immunoreactivity can be a prognostic indicator of prostatic carcinoma, the beta-MSP immunohistochemical distribution has been examined in needle biopsy specimens taken from 96 patients with prostatic carcinoma. Although no significant correlation was found between the beta-MSP immunoreactivity and the histological grade (Gleason score), patients with a positive beta-MSP expression had a significantly better prognosis than those with a negative beta-MSP expression (P = 0.01). Further, a multivariate analysis of six possible parameters (age, clinical stage, histological grade, serum prostatic acid phosphatase, beta-MSP immunoreactivity, and the type of initial treatment) has shown the difference in the beta-MSP immunoreactivity to be a significant, independent, prognostic indicator of prostatic carcinoma (P = 0.04).

Aged↗

Serum LECT2 level as a prognostic indicator in acute liver failure.

In the present study, we investigated the relationship between serum leukocyte cell-derived chemotaxin2 (LECT2) levels and liver function in patients with acute liver failure, and its use as a prognostic indicator. We studied six acute liver failure patients (two women, four men; 49.8 +/- 20.7 years old) admitted to our hospital in 2002. These patients had diagnoses of fulminant hepatitis due to acute liver failure (1) from congestive heart failure; (2) from portal venous gas, and (3) from postoperative disseminated intravascular coagulation (DIC). We measured serum LECT2, GOT, and GPT levels, the last two being inversely proportionate to the serum LECT2 levels. When the serum GPT levels peaked, the serum LECT2 levels were the lowest. When the liver function recovered, serum LECT2 levels increased. Three of four patients died due to liver failure, one to congestive heart failure. Maximum serum LECT2 levels among the expired group were significantly lower than those among the alive group (0.96 +/- 0.8 ng/mL vs 12.9 +/- 4.3 ng/mL). Serum LECT2 levels may be a prognostic indicator of recovery from liver failure. The present study suggests that in clinical medicine LECT2 participates in regeneration after injury of hepatocytes.

Adult↗

Intense p53 staining is a valuable prognostic indicator for poor prognosis in medulloblastoma/central nervous system primitive neuroectodermal tumors.

UNLABELLED: Intense p53 immunostaining may predict for a poor prognosis in central nervous system primitive neuroectodermal tumor of childhood. BACKGROUND: Medulloblastoma is a common childhood primary brain tumor. Potential prognostic indicators for patients with local disease are age, extent of resection, and gender. However, none of these are well established. Immunohistologic staining is a potentially useful means to identify high-risk patients. The purpose of this clinical pathologic study was to investigate the prognostic significance of GFAP, synaptophysin, Ki-67, and p53 immunostaining in medulloblastoma/central nervous system primitive neuroectodermal tumors (CNS PNETs.) MATERIALS AND METHODS: The records of 40 patients with CNS PNETs were reviewed. Their surgical specimens were immunostained for p53, glial fibrillary acidic protein (GFAP), synaptophysin, and Ki-67. The p53 specimens were scored blindly for the intensity of staining of nuclei (intense vs weak) and the quantity of cells stained. The Ki-67, GFAP, and synaptophysin specimens were analyzed for quantity of cells stained. RESULTS: Ten patients' specimens stained intensely for the p53 protein. Eleven had weakly staining nuclei. Nineteen specimens had no staining. The patients with specimens that stained intensely had a statistically significant decreased disease free survival (P = 0.03). Mere presence or quantity of p53 nuclear staining did not correlate with disease free survival. Immunohistochemical staining for Ki-67, GFAP, and synaptophysin did not correlate with disease free survival. Clinical parameters of age, gender, and extent of resection also did not approach statistical significance for disease free survival. CONCLUSION: Intense nuclear staining for p53 was the only variable in this clinical pathologic study that reached statistical significance for disease free survival. This suggests that intense staining for p53 may be the most important prognostic indicator for non-metastatic CNS PNETs. p53 Immunostaining with antibodies against p53 in CNS PNETs should be studied in a multi-institutional setting with larger numbers of patients.

Adolescent↗

Apoptosis as an independent prognostic indicator in squamous cell carcinoma of the esophagus.

Apoptosis plays a crucial role in determining net cell proliferation and cell turnover in various tumors. The rate of apoptosis in tumor cells has been reported to be a useful prognostic indicator in colorectal carcinoma. We examined apoptosis in 72 specimens of esophageal squamous cell carcinoma, by the terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) digoxigenin-nick end labeling (TUNEL) method. We examined correlation of apoptosis with outcome, clinicopathological features, and expression of the apoptosis-related proteins p53 and Bcl-2. The percentage of apoptotic cells, or apoptotic index (AI), ranged from 0.8 to 9.4 (mean: 3.47; SD: 2.02). Overall, 5-year survival of patients with high AI (AI > or = 5.0; n = 18) tumors was significantly higher than that of patients with low AI tumors (AI < 5.0; n = 58; 76.9% versus 44.9%; P = 0.042). AI did not correlate significantly with the clinicopathological features of patient age and sex, depth of tumor and histological differentiation, lymph node metastasis, lymphatic invasion, or venous invasion. In p53-negative tumors, the AI was significantly higher than in p53-positive tumors. We concluded that AI may be a useful prognostic indicator in esophageal squamous cell carcinoma following curative surgery, and that apoptosis in this tumor is related to relative underexpression of p53 protein.

Adult↗

Expression of reversion-inducing-cysteine-rich protein with Kazal motifs (RECK) as a prognostic indicator in gastric cancer.

In this study the expression levels of reversion-inducing-cysteine-rich protein with Kazal motifs (RECK) in gastric cancer cell lines and tissues have been analysed in order to assess their value as a prognostic indicator. The expressions of RECK, activated matrix metalloproteinase (MMP)-7, and vascular endothelial growth factor (VEGF) in gastric cancer tissues and cell lines were evaluated by Western blot analysis; and MMP-2 and MMP-9 were evaluated by gelatin zymography. RECK expression in the context of gastric cancer was also compared with various clinicopathologic parameters and compared to the expression of activated MMP-7, MMP-2, and MMP-9. Fifty-two percent of the 102 gastric cancer tissues and 81.8% of the 11 gastric cancer cell lines exhibited reduced RECK expression. We also detected a significant inverse correlation between RECK expression and macroscopic tumour growth (P=0.018), lymphatic invasion (P=0.018), lymph node metastasis (P=0.000), stage (P=0.000), and MMP-9 (P=0.039). No correlation between RECK expression and MMP-7 and MMP-2, VEGF were detected. Our data strongly supports the hypothesis that RECK is a suppressor of malignancy, and constitutes a good prognostic indicator in gastric cancer.

Adult↗