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Prognostic significance of K-ras, p53, bcl-2, PCNA, CD34 in radically resected non-small cell lung cancers.

The aim of this study was to investigate the prognostic significance of a panel of biological parameters in patients with radically resected non-small cell lung cancers (NSCLC). 269 cases with pathological stage I-IIIA NSCLC were retrospectively analysed. Immunohistochemistry was performed to detect protein expression of p53, bcl-2, proliferating cell nuclear antigen (PCNA) and CD34. Polymerase chain reaction (PCR)/direct nucleotide sequencing method was used to detect mutations in K-ras (codons 12, 13, 61, exons 1-2). The Kaplan-Meier estimates of survival were calculated for clinical and biological variables using the Cox model for multivariate analysis. Histological subtype and the pathologic tumour extension (pT) were the most powerful clinical-pathological prognostic factors for survival (P=0.030 and P=0.031, respectively), whereas among the biological parameters, p53 overexpression (P=0.032) and K-ras mutation (P=0.078) had a negative prognostic role, as demonstrated by multivariate analysis. Conversely, bcl-2, PCNA and CD34 expression were not correlated with survival. Statistically significant associations between p53 expression and the squamous cell carcinoma (SCC) subtype, bcl-2 expression and SCC subtype, K-ras mutation and p53 negative expression, p53 and bcl-2, bcl-2 and PCNA overexpression were observed. In conclusion, some biological characteristics such as the K-ras and p53 status may provide useful prognostic information in resected NSCLC patients, in addition to the classical clinico-pathological parameters. However, further studies are needed to clarify the value of adopting biological prognostic factor into clinical practice.

Adult↗

Design of a prognostic index score for metastatic nasopharyngeal carcinoma.

The survival outcome of patients with systemic cancer differs significantly between individuals even within the same tumour type. We set out to illustrate this by analysing the factors determining survival in patients with metastatic disease from nasopharyngeal carcinoma (NPC) and to design a scoring system based on these prognostic factors. Patients referred between January 1994 and December 1999 were retrospectively analysed. Factors analysed included patient (age group, gender, performance status (BS) at diagnosis of metastases), disease (number of metastatic sites, specific metastatic sites, disease-free interval (DFI), metastases at presentation, presence of locoregional recurrence), and laboratory factors (leucocyte count, haemoglobin level, albumin level). Univariate and multivariable analyses were performed using the Cox proportion hazards model. A numerical score was derived from the regression coefficients of each independent prognostic variable. The prognostic index score (PIS) of each patient was calculated by totalling up the scores of each independent variable. Independently significant, negative prognostic factors were liver metastasis, lung metastasis, anaemia, poor PS, distant metastasis at initial diagnosis, and a DFI of <6 months. Three prognostic groups based on the PIS were obtained: (i) good risk (PIS=0-6); (ii) intermediate risk (7-10); (iii) poor risk (>or=11). The median survivals for these groups were 19.5, 10, and 5.8, months, respectively, (log rank test: P<0.0001). The variable prognosis of patients with disseminated NPC can be assessed by using easily available clinical information (patient, disease and laboratory factors). The PIS system will need to be validated on prospectively collected data of another cohort of patients.

Adult↗

A prognostic score for patients resected for gastric cancer.

This paper describes the construction, validation and use of a simple prognostic score suitable for predicting survival of patients undergoing a curative gastric resection. Using death from all causes as outcome, the prognostic significance of age, sex, tumour site, stage of disease (nodal status and wall invasion), surgical treatment and histological type was investigated in a set of 213 patients recruited in a multi-centre clinical trial. A Weibull multiple regression model was adopted to evaluate the joint effect of these variables on survival. From a full model, containing all the variables, a final parsimonious model was obtained by means of a backward selection procedure. The prognostic score is based on the final model, including four variables which are easily detected in every institution: age, wall invasion, site of tumour, and nodal status. Three groups of patients with different probabilities of surviving 5 years from surgery were identified: group I (survival probability > or = 70%), group II (30%-69%) and group III (< 30%). The prognostic score, obtained from the multicentre trial patients, was tested on a set of 135 consecutive patients in an independent institution, confirming its reliability in predicting survival. The score system presented can supply a simple tool for classifying patients radically operated for gastric cancer into three well discriminated groups from the prognostic point of view.

Age Factors↗

Obvious peritumoral emboli: an elusive prognostic factor reappraised. Multivariate analysis of 1320 node-negative breast cancers.

This study was conducted to determine the prognostic influence of obvious peritumoral vascular emboli as prospectively determined by a simple routine slide examination in patients with operable node-negative breast cancer. Obvious peritumoral emboli (OPE) were defined by the presence of neoplastic emboli within unequivocal vascular lumina (including both lymphatic spaces and blood capillaries) in areas adjacent to but outside the margins of the carcinoma. OPE were assessed routinely on 5 microns thick haematoxylin and eosin-stained sections for each of 1320 primary operable node-negative breast cancers from 1975 to 1992 at our institution. OPE and other prognostic variables (tumour size, SBR grade, oestrogen and progesterone receptor status) were correlated to overall survival (OS) and metastasis-free interval (MFI) by means of univariate and multivariate analysis with a median follow-up of 103 months. OPE were found in 19.5% of tumours. In univariate analysis, OPE were related to tumour size (P = 6.3 x 10(-5)) and histologic grade (P = 4.9 x 10(-7)). Statistically significant correlations were found with OS (P = 4.6 x 10(-5)) and MFI (P = 6.4 x 10(-9)). Furthermore, in multivariate analysis, OPE was an independent prognostic variable, the most predictive factor for MFI (P = 7.7 x 10(-7)) before tumour size and grade, and was second after tumour grade for OS (P = 0.002). This study on a large unicentric series and with a long follow-up confirms the prognostic significance of vascular emboli in patients with operable node-negative breast carcinoma. Importantly, vascular emboli were found to be accurately detectable by a simple routine and non-time-consuming method. Therefore, such obvious vascular emboli should be considered as an important cost-effective, prognostic variable in patients with node-negative breast carcinoma.

Adult↗

The prognostic value of p53 for long-term and recurrence-free survival following radical prostatectomy.

In the present study, 76 specimens (T1-T4) from 76 randomly selected patients undergoing radical prostatectomy at Hannover University as well as in the Josef Hospital Regensburg (13 patients) between 1980 and 1992 for whom tissue sections for immunohistochemical investigation were available, were investigated for different biological and clinical characteristics as predictors for long-term and recurrence-free survival: age, depth of tumour infiltration, histological grade, lymph node status, as well as overexpression of the p53 protein (monoclonal antibody DO-1). After a median follow-up of 50 months, 6 of 18 patients (33%) with more than 20% of tumour cells stained positively for p53 died from tumour progression compared with 9 of 58 patients (16%) with less than 20% of tumour cells positive for p53. During univariate analysis, p53 overexpression (P = 0.011), histological grading (P = 0.009) and tumour stage (P = 0.024) were significant prognostic factors for survival, among which only p53 overexpression (P = 0.026) remained an independent significant predictor in multivariate analysis. Additionally, 18 of 66 patients (27%) with less than 40% positivity for p53 suffered tumour recurrence in contrast to 6 of 10 patients (60%) with more than 40% tumour cells exhibiting a positive staining reaction. In multivariate analysis, p53 overexpression was identified as the only prognostic parameter for recurrence-free survival (P = 0.005). Prospective studies are needed to confirm the independent prognostic potential of p53 overexpression in patients with localised prostate cancer. The availability of more refined prognostic factors should assist decision making regarding the value of radical prostatectomy versus a surveillance strategy for prognostically defined subgroups of patients.

Aged↗

Prognostic value of QT interval parameters in type 2 diabetes mellitus: results of a long-term follow-up prospective study.

The prognostic importance of electrocardiographic ventricular repolarization QT parameters (maximum rate-corrected QT interval-QTcmax, QT interval dispersion-QTd, and QTcd), in relation to other risk markers, on cardiovascular and cardiac mortality, and on total fatal or nonfatal cardiovascular events, was evaluated prospectively in 471 type 2 diabetic outpatients. During a median follow-up of 57 months (range: 2-84), 121 (25.7%), patients died, 44 (36.3% of them) from cardiovascular causes and 106 (22.5%) fatal or nonfatal cardiovascular events were observed. In Cox proportional hazards multivariate analysis, both QTd and QTcmax were independent predictors of cardiovascular and cardiac mortality (hazard ratio [HR]: 1.34, 95% confidence interval [95% CI]: 1.12-1.59, for each 10-ms increments in QTd and HR: 1.17, 95% CI: 1.03-1.21 for 10-ms increments in QTcmax, for cardiovascular mortality). They were also predictors of total fatal or nonfatal cardiac and cardiovascular events (HR: 1.18, 95% CI: 1.05-1.33 for QTd and HR: 1.09, 95% CI: 1.04-1.15 for QTcmax). Additional independent prognostic markers for total cardiovascular events were the presence of previous cardiac disease, cerebral or peripheral vascular disease, age, male gender, known diabetes duration, heart rate, and serum triglycerides. Excluding patients with prior cardiac disease did not change significantly the prognostic performance of QTd but decreased that of QTcmax. In conclusion, QT interval parameters give additional prognostic information in patients with type 2 diabetes mellitus, beyond that obtained from traditional risk factors. QT interval dispersion seems a better prognostic marker than maximum QT interval, particularly in patients without previous cardiac diseases.

Adult↗

Diagnostic and prognostic values of CA 19-9 and CEA in periampullary cancers.

BACKGROUND: The roles of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) in periampullary cancers have not been clearly established. Diagnostic and prognostic values of these two tumor markers were clarified in this study. STUDY DESIGN: Preoperative serum levels of CEA and CA 19-9, and clinicopathologic features were retrospectively reviewed in 143 surgical patients with periampullary cancer from 1989 to 1997. RESULTS: There were 86 resectable and 57 unresectable periampullary cancers. CA 19-9 demonstrated significantly higher sensitivity in detecting these cancers than CEA. The cancer with unresectable lesion, total bilirubin >7.3 mg/dL, or tumor size >2 cm tended to associate with higher CA 19-9 level. CEA level was significantly higher in the tumor >2 cm, not in the tumor < or =2 cm. CA 19-9 was a significant prognostic factor in both resectable and unresectable periampullary cancers, but CEA was significant only in the resectable group. Multivariate analysis revealed that independent prognostic factors included CA 19-9, resectability, primary tumor, and stage, and CA 19-9 was the most important one. CONCLUSION: CA 19-9 provided more important diagnostic and prognostic values than CEA in periampullary cancers and was the most important independent prognostic factor for periampullary cancers. This study recommends serum CA 19-9 as an adjunct in detecting periampullary cancers, in evaluating resectability, and in predicting prognosis.

Ampulla of Vater↗

Surfing prognostic factors in head and neck cancer at the millennium.

The ability to reliably predict cancer outcome could tailor therapy to the aggressiveness of the tumour to achieve the best results in terms of loco-regional control, overall survival and quality of life. Retrospective and prospective clinical trials involving large series of patients have validated some predictive clinical and pathological factors, whereas the utility of many other prognostic factors has not been established. This has led to some confusion in clinical practice. In order to clarify the significance, role and cost of these prognostic factors we carried out a Medline search of all papers published between 1993 and 1998 concerning the reliability and cost of markers with prognostic significance, in head and neck squamous cell carcinoma, and assessed the results according to a number of criteria relating to reliability and cost. Regarding reliability we classified prognostic factors into: (1) those with a proven significance based on the fact that they were unanimously reported as having an independent statistical correlation with outcome and prognosis; and (2) those for which results were not unanimous, and which significance is still controversial. Cost analysis showed a substantial difference between validated tests which are of low cost and experimental tests which are expensive. Based on these data regarding both the reliability and cost of each prognostic factor, we propose guidelines for their use in clinical practice in the year 2000.

Biomarkers, Tumor↗

The fucosylation index of serum alpha-fetoprotein as useful prognostic factor in patients with hepatocellular carcinoma in special reference to chronological changes.

Aim of this study was to establish fucosylation index (FI) of alpha-fetoprotein (AFP) before and after initial treatment as a useful prognostic factor in patients with hepatocellular carcinoma (HCC). One hundred ninety-seven patients with HCC from 1990 to 2000, in whom an increment of serum AFP concentrations more than 30 ng/ml was observed before treatment, were examined in the present study. Enrolled patients with HCC underwent transcatheter arterial embolization, chemoembolization, percutaneous ethanol injection and/or percutaneous microwave coagulation therapy. The current patients status was confirmed as of the end of March 2001. FI was determined by crossed immunoaffinoelectrophoresis in the presence of Lens culinaris agglutinin (LCA). FI of AFP was defined as the percentage of the LCA-reactive species in total AFP (same as L3 fraction). When the tentative discriminating line of FI was set at 18%, the mean survival rate in the HCC group, whose FI-1 (before treatment) was higher than 18% (high FI), was significantly lower than that in another HCC group, whose FI-1 was equal to or less than 18% (low FI) by the generalized Wilcoxon test and the log rank test (P<0.0001). There were statistical significant differences of survival rate when FI-2 (2 months after treatment) and FI-3 (at the time of HCC recurrence or 2 years after treatment in the case of no recurrence) were introduced in the same analysis. Additionally, statistical significant differences of survival rates were obtained between HCC groups with high and low FI-1 when the patient stage was limited to II, III, IVA or IVB. The HCC group, FI-1, FI-2 and FI-3 of which were persistently equal to or less than 18%, showed considerably better prognosis than the group, whose FI-1, FI-2 and FI-3 were persistently higher than 18%. The univariate analysis in the prognostic factor by the Cox's proportional hazards model showed that FI-1, FI-2 and FI-3 were independent prognostic factors. The present study indicates that measuring FI from the sera before and after the treatment serves as a new prognostic indicator and may improve prognostic estimates and appraisal of therapeutic outcome in patients with HCC.

Journal Article↗

4-year mortality in patients with non-small-cell lung cancer: development and validation of a prognostic index.

BACKGROUND: Lung cancer is the commonest cause of death due to cancer in the world. Non-small-cell lung carcinoma (NSCLC) represents about 80% of overall lung cancer cases worldwide. An accurate predictive model of mortality in patients with NSCLC could be useful to clinicians, policy makers, and researchers involved in risk stratification. The objective of this study was to develop and validate a simple prognostic index for 4-year mortality in patients with NSCLC by use of information obtained at the time of lung cancer diagnosis. METHODS: In 2000, 4669 patients with histologically or cytologically proven NSCLC were enrolled prospectively from 137 pneumology departments in French general hospitals. Patients not lost to follow-up (n=4479) were randomly assigned to the development cohort (n=2979) or the validation cohort (n=1500). Every patient's physician completed a standard and anonymous questionnaire. We used a Cox model to identify variables independently associated with mortality and weighted the variables to create a prognostic index. FINDINGS: Median follow-up for survivors was 49 months (IQR 46-51). There were 2585 deaths (87%) in the development cohort and 1310 deaths (87%) in the validation cohort. Five independent predictors of mortality were identified: age (>70 years, 1 point); sex (male, 1 point); performance status at diagnosis (reduced activity, 3 points; active >50%, 5 points; inactive >50%, 8 points; and total incapacity, 10 points); histological type (large-cell carcinoma, 2 points); and tumour-node-metastasis (TNM) staging system (IIA or IIB, 3 points; IIIA or IIIB, 6 points; and IV, 8 points). The minimum and maximum possible point scores were 0 and 22, respectively. Scores of the prognostic index were strongly associated with 4-year mortality in the development cohort: 0-1 points predicted a 35% (95% CI 28-43) risk, 2-4 points a 59% (52-66) risk, 5-7 points a 77% (72-81) risk, 8-10 points an 88% (85-90) risk, 11-14 points a 97% (96-98) risk, and 15-22 points a 99% (97-100) risk. The corresponding percentages in the validation cohort were 36% (24-47), 60% (50-70), 77% (71-83), 89% (86-93), 96% (95-98), and 99% (98-100), respectively. The prognostic index showed good discrimination, with mean bootstrap c statistics of 0.85 (95% CI 0.84-0.86) in the development cohort and 0.86 (95% CI 0.85-0.87) in the validation cohort. INTERPRETATION: This prognostic index, incorporating personal, tumour, and functional information would be helpful in guiding patient management, resource use, and the design of clinical trials.

Adult↗

Prognostic relevance of anamnestic and diagnostic parameters in low-frequency hearing impairment.

Low-frequency hearing impairment (LFHI) is mainly attributed to endolymphatic hydrops and has a great variety of possible outcomes. At present, no conservative therapeutic regimen has proven to be 'gold-standard', and information about the prognostic indicators of LFHI is scarce. In a retrospective investigation, we evaluated the records of 90 patients who had been treated with infusions improving blood perfusion. In patients lacking complete remission, dehydration infusion therapy was added. We also undertook audiometric follow up. We calculated the outcomes after infusion therapy, dehydration therapy and after long-time hearing follow up, and we determined the prognostic relevance of several parameters of anamnesis and clinical examination to outcomes, for both therapeutic interventions and long-time hearing. The prognosis of LFHI was significantly correlated to certain anamnestic and clinical parameters; a short duration of the disease, lack of vertigo and female gender implied a better outcome. The pretherapeutic hearing threshold was an important prognostic factor; the outcome was significantly worse in patients with distinct hearing impairment in low or high frequencies, compared with that in patients with little hearing loss. Whereas vertigo was a negative prognostic factor, the results of quantitative vestibular testing were irrelevant to the outcome. The glycerol test failed to predict the effectiveness of dehydration therapy and lacked any value in predicting prognosis. These results allow the clinician to focus the anamnesis and diagnostic examination on prognostically relevant parameters, thus enabling a better estimation of the long-term disease course and improved counselling of patients. Furthermore, these results help to distinguish valuable from irrelevant diagnostic procedures.

Acetazolamide↗

The importance of accounting for the uncertainty of published prognostic model estimates.

OBJECTIVES: Reported is the importance of properly reflecting uncertainty associated with prognostic model estimates when calculating the survival benefit of a treatment or technology, using liver transplantation as an example. METHODS: Monte Carlo simulation techniques were used to account for the uncertainty of prognostic model estimates using the standard errors of the regression coefficients and their correlations. These methods were applied to patients with primary biliary cirrhosis undergoing liver transplantation using a prognostic model from a historic cohort who did not undergo transplantation. The survival gain over 4 years from transplantation was estimated. RESULTS: Ignoring the uncertainty in the prognostic model, the estimated survival benefit of liver transplantation was 16.7 months (95 percent confidence interval [CI], 13.5 to 20.1), and was statistically significant (p < .001). After adjusting for model uncertainty using the standard errors of the regression coefficients, the estimated survival benefit was 17.5 months (95 percent CI, -3.9 to 38.5) and was no longer statistically significant. An additional adjustment for the correlation between regression coefficients widened the 95 percent confidence interval slightly: the estimated survival benefit was 17.0 months (95 percent CI: -4.6 to 38.6). CONCLUSIONS: It is important that the precision of regression coefficients is available for users of published prognostic models. Ignoring this additional information substantially underestimates uncertainty, which can then impact misleadingly on policy decisions.

Cohort Studies↗

Predicting final disposition after stroke using the Orpington Prognostic Score.

BACKGROUND: Prediction of outcome after stroke is important for triage decisions, prognostic estimates for family and for appropriate resource utilization. Prognostication must be timely and simply applied. Several scales have shown good prognostic value. In Calgary, the Orpington Prognostic Score (OPS) has been used to predict outcome as an aid to rehabilitation triage. However, the OPS has not been assessed at one week for predictive capability. METHODS: Among patients admitted to a sub-acute stroke unit, OPS from the first week were examined to determine if any correlation existed between final disposition after rehabilitation and first week score. The predictive validity of the OPS at one week was compared to National Institute of Health Stroke Scale (NIHSS) score at 24 hours using logistic regression and receiver operator characteristics analysis. The primary outcome was final disposition after discharge from the stroke unit if the patient went directly home, or died, or from the inpatient rehabilitation unit. RESULTS: The first week OPS was highly predictive of final disposition. However, no major advantage in using the first week OPS was observed when compared to 24h NIHSS score. Both scales were equally predictive of final disposition of stroke patients, post rehabilitation. CONCLUSIONS: The first week OPS can be used to predict final outcome. The NIHSS at 24h provides the same prognostic information.

Activities of Daily Living↗

The differing prognostic utility of exercise radionuclide ventriculography in coronary artery disease patients with and without prior myocardial infarction.

UNLABELLED: Previous studies have documented the prognostic utility of left ventricular ejection fraction response to exercise primarily in populations without prior myocardial infarction. We undertook a study to assess the prognostic utility of exercise left ventricular ejection fraction and segmental wall motion response during exercise radionuclide ventriculography in coronary artery disease patients with and without prior myocardial infarction. METHODS: We examined the comparative prognostic utility of left ventricular ejection fraction and segmental wall motion response during upright bicycle exercise radionuclide ventriculography in 419 coronary artery disease patients with (n = 217) and without (n = 202) prior myocardial infarction using univariate and multivariate hierarchical regression analyses. RESULTS: During an average followup period of 61 months, 96 patients (23%) suffered cardiac events, including 55/217 (25%) of the patients with prior myocardial infarction and 41/200 (21%) of the patients without prior myocardial infarction (p = ns). Both cumulative Kaplan-Meier survival analyses and stepwise hierarchical Cox survival analyses demonstrated that peak left ventricular ejection fraction < 55% was a significant predictor of cardiac events in patients without prior myocardial infarction (p = 0.04), whereas an exercise wall motion worsening score > or = 2 was a significant predictor in patients with a prior myocardial infarction (p = 0.0001). CONCLUSIONS: The prognostic utility of exercise radionuclide ventriculography variables differ according to the presence or absence of prior myocardial infarction. Global function, assessed by peak left ventricular ejection fraction, adds the greatest prognostic information in patients without prior myocardial infarction, whereas regional function, assessed by exercise wall motion worsening, is the best predictor among patients with prior myocardial infarction.

Adult↗

Invasion marker PAI-1 remains a strong prognostic factor after long-term follow-up both for primary breast cancer and following first relapse.

In 1991, our group was the first to report the prognostic strength of plasminogen activator inhibitor type 1 (PAI-1) in primary breast cancer. The prognostic impact of invasion markers PAI-1 and urokinase-type plasminogen activator (uPA) on disease-free survival (DFS) and overall survival (OS) in breast cancer has since been independently confirmed. We now report on the prognostic impact of PAI-1 and uPA after long-term median follow-up of 77 months for our cohort (n = 316). Levels of uPA, PAI-1, and cathepsin D were determined in tumor tissue extracts by immunoenzymatic methods. S-phase fraction (SPF) was measured flowcytometrically in paraffin sections. Using log-rank statistics, optimized cutoffs were found for PAI-1 (14 ng/mg), uPA (3 ng/mg), cathepsin D (41 pmol/mg), and SPF (6%). In all patients, various factors (PAI-1, uPA, nodal status, SPF, cathepsin D, grading, tumor size, hormone receptor status) showed significant univariate impact on DFS. In Cox analysis, only nodal status (p < 0.001, RR: 3.1) and PAI-1 (p < 0.001, RR: 2.7) remained significant. In node-negative patients (n = 147), PAI-1, uPA, and SPF had significant univariate impact on DFS, whereas in Cox analysis, only PAI-1 was significant. PAI-1 was also significant for DFS within subgroups defined by established factors. In CART analysis, uPA enhanced the prognostic value of PAT-1 and nodal status for determination of a very-low-risk subgroup. For OS, only lymph node status and PAI-1 were significant in multivariate analysis. PAI-1 levels in the primary tumor were also a significant prognostic marker for survival after first relapse in both univariate and multivariate analysis.

Adult↗

Prognostic implications of expression of the cell cycle inhibitor protein p27Kip1.

Mitogenic and growth inhibitory signals influence the activity of a family of cyclin dependent kinases (cdks). p27 is an important cdk inhibitor, acting in G1 to inhibit cyclin-cdks. As negative growth regulators, the cdk inhibitors may function as tumor suppressors. While the p16 gene plays a tumor suppressor role in cancers, p27 gene mutations have been identified only rarely. While high levels of p27 protein are expressed in normal human mammary epithelium, loss of p27 is frequent and is of independent prognostic significance in breast cancers. Low p27 is also a poor prognostic factor in colon, gastric, esophageal, lung, and prostate carcinomas, and enhanced proteasomal degradation may underlie loss of p27 in tumor cells. Loss of p27 has not been significantly correlated with tumor proliferation in a number of studies and may reflect alterations in differentiation and adhesion-dependent growth regulation germane to oncogenesis and tumor progression. Efforts to confirm the prognostic value of p27 are under way in a number of large breast cancer studies. These studies may also indicate whether loss of p27 in association with other traditional or novel markers has greater prognostic potential than each factor alone. p27 immunostaining is inexpensive and reliable and may become part of the routine histopathologic processing of tumors in the near future. Widespread application of p27 in prognostic testing will require greater uniformity in scoring techniques and determination of the cut off levels which distinguish individuals at high and low risk of cancer recurrence and death. Finally, the greatest utility of p27 may lie in the information it sheds on the biology of aberrant growth regulation in breast cancer and the potential to use this in the generation of novel therapeutic strategies.

Breast Neoplasms↗

Quantitative measurement of soluble cytokeratin fragments in tissue cytosol of 599 node negative breast cancer patients: a prognostic marker possibly associated with apoptosis.

Apoptosis is associated with caspase-mediated proteolysis of Type I (K18 and K19) cytokeratins. We previously showed a positive association between the levels of tissue polypeptide antigen (TPA), that recognizes cytokeratins K8, K18, and K19 fragments, and induced apoptosis in breast cancer cell lines. The aim of the present study was to evaluate the interrelationships between TPA, steroid receptors, and p53, and their joint prognostic role in node-negative breast cancer patients not treated with adjuvant therapies. Age and pT were also considered since they are known prognostic factors. Five hundred and ninety-nine cases with N- breast cancer were evaluated (median follow-up: 60 months). TPA was measured by an immunoradiometric assay and p53 by an immunochemiluminescent assay in tumor cytosol. Multiple correspondence analysis was used to study the associations among variables. Their prognostic role (univariate analysis) and their joint effect (multivariate analysis) on RFS were investigated with Cox regression models. TPA showed a direct association with ER and PgR. Higher p53 values were weakly associated to low values of ER, PgR, and TPA. Younger age was related to low and intermediate values of ER and PgR and to low p53 values, while older age was related to high values of ER. Multivariate analysis showed a significant prognostic impact for pT, age, ER, and TPA. Among the interactions considered clinically relevant, only that between ER and age was found. RFS estimated values were poorer in cases with lower than in those with higher TPA values, both in patients expected to have a poor (pT2, young age, low ER) and a better prognosis (pT1, older age, high ER). From the findings of the present study we can draw the following conclusions: The relationship of TPA with prognosis gives an additional contribution to pT, age, and steroid receptors in N- breast cancer; TPA may be considered the first marker of apoptosis measured with a fully standardized quantitative method in tumor cytosol and could be evaluated in prognostic indexes including markers related to different biological mechanisms.

Adult↗

Clinical and prognostic characteristics associated with age and gender in acute myocardial infarction: a multihospital perspective in the Murcia region of Spain.

Age and female gender have been associated with poor prognosis in acute myocardial infarction (AMI). Data currently available about the prognostic significance of gender in AMI might well have led to inappropriate/incomplete conclusions. A multicenter, prospective study on 1239 patients with AMI was conducted. Clinical characteristics, complications during the acute phase and one-year follow-up were monitored. Women constituted 24.1% of all patients. Female patients were older with more prevalence of diabetes, hypertension, and previous congestive heart failure. Compared with men, the following complications were more frequently found in women: heart failure, 43% vs. 22% (p < 0.001); reinfarction, 5% vs. 2% (p < 0.05); use of pacemaker, 7% vs. 4% (p < 0.05). Women had higher mortality: early, during the first 24 hours post-admission, 10.7 vs. 3.1%; in-hospital, 23% vs. 8.1%; and 1-year, 33.7% vs. 16% (p < 0.001 for all the 3 cases of mortality). In the age-groups considered (<65, 65-74, and > or =75 years), 1-year mortality increased exponentially with ageing in men: 7.8%, 21.3%, and 38.9%, whereas in women the figures were: 15.3%, 41.5%, and 38.8%. Multivariate analysis showed that, among other variables, age and female gender had independent prognostic value for in-hospital mortality whereas gender lost its prognostic significantly for 1-year mortality. Multivariate analysis restricted to those patients aged over 75 years showed that age but not gender had independent prognostic value. In conclusion, age and female sex have independent prognostic value for predicting mortality in patients with AMI. Mortality increases exponentially with ageing in men whereas it stabilises in the case of women over 65 years. Female gender loses its independent value for predicting mortality in patients over 75 years.

Age Distribution↗