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p53 and mdm2 as prognostic indicators in patients with epithelial ovarian cancer: a multivariate analysis.

OBJECTIVE: The aim of the study was to investigate the prognostic significance of p53 and mdm2 protein expressions in epithelial ovarian cancer and their relationship with the clinicopathological variables. METHODS: Tumor biopsy specimens from 82 patients who were homogenously treated were examined immunohistochemically for expression of p53 and mdm2 proteins. Univariate and multivariate analyses were performed for prognostic factors, and correlations with clinicopathological parameters were examined. RESULTS: Fifty-four percent and 33% of cases stained positive for p53 and mdm2, respectively. p53 expression was associated with serous type, higher grade, positive cytology, residual tumor and stage of the disease. mdm2 expression predicted of chemosensitivity and it was related with higher grade but not with other clinicopathological variables. Significantly poorer survival was seen for those with p53 (P < 0.05) or mdm2 (P < 0.01) positive tumors than those with negative p53 or mdm2 staining. Coexpression of p53 and mdm2 was also related to poor outcome (P < 0.05). Multivariate analysis revealed that FIGO stage, mdm2 expression, response to chemotherapy and optimal cytoreduction were significant independent prognostic and predictive factors of survival. CONCLUSION: Although our findings showed that mdm2 may be used as a prognostic indicator in patients with epithelial ovarian cancer, these results should be supported by more and larger studies.

Biomarkers, Tumor↗

Multivariate analysis of human immunodeficiency virus type 1 neutralization data.

We report on the use of spectral map analysis of the inter- and intraclade neutralization data of 14 sera of human immunodeficiency virus type 1 (HIV-1)-infected individuals and 16 primary isolates, representing genetic clades A to H in group M and group O. This multivariate analysis has been used previously to study the interaction between drugs and receptors and between viruses and antiviral compounds. The analysis reveals the existence of neutralization clusters, not correlated with the known genetic clades. The structural factors that have been identified may correlate with the most important neutralization epitopes. Three key primary HIV-1 isolates, which allow discrimination of sera that are likely or unlikely to neutralize primary isolates from most of the genetic clades, were identified. Our method of analysis will facilitate the evaluation as well as the design of suitable HIV-1 vaccines, which induce high-titer interclade cross-neutralizing antibodies.

Acquired Immunodeficiency Syndrome↗

Relationship of lipoprotein(a) and its phenotypes with the albumin excretion rate in diabetic patients: a multivariate analysis.

BACKGROUND/AIM: The possible association between lipoprotein(a) [Lp(a)] and albumin excretion rate (AER) is a topic that has generated conflicting views. The aim of this study was to determine the relationship between serum Lp(a) concentrations and AER in diabetic patients, taking into account Lp(a) phenotypes in a multivariate analysis. METHODS: For this purpose 191 consecutive diabetic patients (69 type 1 and 122 type 2) were included in the study. Lp(a) was determined by ELISA and its phenotypes by SDS-PAGE followed by immunoblotting. Lp(a) phenotypes were grouped by size in small (F, B, S1, S2), big (S3, S4) and null. RESULTS: Diabetic patients with an AER >20 microg/min presented higher Lp(a) concentrations than patients with an AER <20 microg/min: median 19 mg/dl versus 5 mg/dl (p < 0.0001). The differences remained at a significant level when the type of diabetes was considered. A linear correlation was observed between Lp(a) concentration and AER (type 1: r = 0.32, p = 0.01; type 2: r = 0.25, p < 0.05). The AER was independently correlated with Lp(a) concentrations in a multiple regression analysis (p < 0.01), and Lp(a) was independently associated with the presence of diabetic nephropathy in the logistic regression analysis. The overall frequency distribution of Lp(a) phenotypes differed significantly between patients with or without microalbuminuria (p < 0.05). In addition, the AER (microg/min) was different among the Lp(a) phenotypes: small 55 +/- 122 (median 4.9), big 58 +/- 123 (median 5.7) and null 3 +/- 2 (median 2.3); p = 0.01. The significant difference mainly resulted from low AER (<10 microg/min) detected in all patients with the null phenotype. CONCLUSIONS: In diabetic patients the serum Lp(a) concentration is associated with AER. Thus, the elevated cardiovascular risk observed in diabetic patients with a high AER could be related to the Lp(a) concentration. Finally, patients with the null Lp(a) phenotype can be considered as a group at low risk of the development of diabetic nephropathy.

Adult↗

Multivariate analysis versus vector analysis to assess surgically induced astigmatism.

PURPOSE: To present a multivariate probability computation method for assessing surgically induced astigmatism. SETTING: Department of Ophthalmology, Rennes University Hospital, Rennes School of Medicine, France. METHODS: The multivariate method was used to evaluate 100 patients who had cataract surgery by phacoemulsification. Keratometry was recorded on the day before and 12 days after surgery. Surgically induced astigmatism was assessed by the multivariate method as well as by most of the published vector analysis methods. RESULTS: The mean surgical induced astigmatism (+/- SD) with the multivariate analysis was 1.18 +/- 0.36 diopters (D) for the cylinder power and 25.00 +/- 5.50 degrees for the cylinder axis. With the vector analysis, the mean surgically induced astigmatism was 1.67 +/- 0.54 D with the Naylor, Jaffe, and Holladay methods; 0.45 +/- 0.30 D with the latest Naeser method; 1.34 +/- 0.38 D with the Cravy method (Cravy's vector); and -0.05 +/- 0.42 D for Cravy's delta K. CONCLUSION: Although vector methods constitute interesting geometrical models, their number and their lack of linearity and explicit expression of results make them unsuitable for statistical analysis. Instead, a reliable, easily programmable method that uses existing software is recommended.

Astigmatism↗

Use of multivariate analysis for optimization of separation parameters and prediction of migration time, resolution, and resolution per unit time in micellar electrokinetic chromatography.

The optimization of separation parameters in chromatography for better separation and resolution of analytes continues to be a labor intensive procedure usually performed by a trial and error method. A multivariate analysis in the form of multilinear regression (MLR) is used to optimize separation parameters and predict the migration behavior, resolution, and resolution per unit time of achiral (4-chlorophenol, pentachlorophenol, clonazepam, and diazepam) and chiral (1,1'-binaphthyl 2,2'-dihydrogen phosphate (BNP), and 1,1'-bi-2-naphthol (BOH)) compounds in MEKC. Separations of achiral and chiral analytes were performed using an achiral (poly(sodium N-undecylenic sulfate)) molecular micelle and chiral (poly(sodium N-undecanoyl-L-leucylvalinate) or poly(sodium N-undecanoyl-L-isoleucylvalinate)) molecular micelle, respectively, at various operating temperatures, applied voltages, pH values, and molecular micelle concentrations in the BGE. The separation parameters were subsequently used as input variables for MLR models. The models were validated with independent samples. The root-mean-square percent relative error (RMS%RE) is used as a figure of merit for characterizing the performance of the migration time, resolution, and resolution per unit time models. The RMS%RE obtained for predicted migrated times, resolutions, and resolution per unit time of 4-chlorophenol, pentachlorophenol, clonazepam, diazepam, BNP, and BOH ranged between 8 and 19%. The same experimental procedure was used to optimize the separation parameters of six other chiral analytes of different compound class. The predicted migration times, resolutions, and resolution per unit time of the chiral as well as the achiral analytes compare favorably with the experimental migration times and resolutions, indicating versatility and wide applicability of the technique in MEKC.

Chromatography, Micellar Electrokinetic Capillary↗

[Multivariate analysis of prognosis in gastrointestinal stromal tumor].

OBJECTIVE: To identify prognostic factors in patients with gastrointestinal stromal tumors (GIST). METHODS: Hematoxylin and eosin (H&E) stained histopathological slides of tumors from patients with mesenchymal neoplasms growing in the gastrointestinal tract and abdomen were reviewed. Two histologically representative areas were identified and chosen for tissue microarray. Immunohistochemical staining was performed to demonstrate c-kit protein (CD117), CD34, smooth muscle actin, desmin and S-100 protein. The relations of various clinicopathologic features to outcome were analyzed. RESULTS: The overall disease-specific survival of 194 patients was 93.5% at 1 year, 72.1% at 3 years and 63.2% at 5 years. Univariate analysis indicated that the tumor size, mitotic count, primary location, necrosis, high cellularity, mucosal invasion, mixed cell type, hemorrhage, direct tumor invasion of surrounding tissue, male sex, incompleteness of resection, cytologic atypia were significant predictors of survival. Multivariate analysis showed that tumor size, mitotic count, necrosis, direct tumor invasion of surrounding tissue and male sex were poor prognostic signs. CONCLUSION: Tumor size and mitotic count are important prognostic factors. However, to evaluate the prognosis of these tumors, a surgical pathologist should incorporate multiple parameters into their histologic evaluation in attempt to reach an appropriate opinion on the aggressiveness of GIST.

Aged↗

Prognostic factors in neuroendocrine small cell cervical carcinoma: a multivariate analysis.

BACKGROUND: The purpose of this study was to evaluate the clinical and pathologic factors associated with survival in patients with neuroendocrine (NE) cervical carcinoma. METHODS: All patients with NE cervical carcinoma diagnosed between 1979-2001 were identified from tumor registry databases at two hospitals. Data were collected from hospital charts, office records, and tumor registry files. The impact of clinical and pathologic risk factors on the survival of patients with small cell NE carcinoma of the cervix was evaluated using Kaplan-Meier life table analyses and log-rank tests. The independent prognostic factors found to be predictive of survival in univariate analysis were evaluated using Cox regression. All tests were two-tailed with P values < 0.05 considered significant. RESULTS: Thirty-four patients (median age, 42 years) were diagnosed with neuroendocrine cervical carcinoma, which included 21 with International Federation of Gynecology and Obstetrics (FIGO) Stage I disease, 6 with FIGO Stage II disease, 5 with FIGO Stage III disease, and 2 with FIGO Stage IV disease. Seventeen patients underwent a radical and 6 patients underwent a simple hysterectomy. Fourteen women received adjuvant therapy with pelvic radiation and/or cisplatin-based chemotherapy. Ten women received primary radiotherapy with (n = 5) or without (n = 4) chemotherapy and the remaining patient refused therapy. Women with early-stage (Stage I-IIA) disease had median survival rates of 31 months compared with 10 months in the advanced-stage (Stage IIB-IVB) group (P = 0.002). In univariate analysis, advanced stage (P = 0.002), tumor size >2 cm (P = 0.02), margin involvement (P = 0.016), pure versus a mixed histologic pattern (P = 0.04), margin status (P = 0.016), and smoking (P = 0.04) were considered poor prognostic factors. In multivariate analysis, smoking for early-stage patients and stage of disease in the overall population remained as independent prognostic factors of survival. CONCLUSIONS: Smoking and advanced stage are reported to be poor prognostic factors for survival in patients with NE small cell carcinoma of the cervix. Only those with early lesions amenable to extirpation are cured. The role of primary or postoperative radiation with or without chemotherapy is unclear and yields uniformly poor results, particularly in patients with advanced lesions. Clinical trials are needed.

Adult↗

Evaluation by multivariate analysis of the differentiation inhibitory factor nm23 as a prognostic factor in acute myelogenous leukemia and application to other hematologic malignancies.

The differentiation inhibitory factor nm23 can inhibit the differentiation of murine and human myeloid leukemia cells. We recently reported that nm23 genes were overexpressed in acute myelogenous leukemia (AML), and a higher level of nm23-H1 expression was correlated with a poor prognosis in AML, especially in AML-M5 (acute monocytic leukemia). To evaluate the importance of nm23 expression as a prognostic factor in AML, we compared it with other putative prognostic factors in AML. An analysis of the correlation between nm23 expression and the clinical parameters of 110 patients with AML demonstrated that increased nm23-H1 mRNA levels were associated with resistance to initial chemotherapy and with reduced overall survival. Multivariate analysis using Cox's proportional hazard model also showed that elevated nm23-H1 mRNA levels significantly contributed to the prognosis of patients with AML. Especially in AML-M5, nm23-H1 status was the most important prognostic factor. Furthermore, to determine whether we can apply the results observed in AML to other hematologic malignancies, we investigated the relative levels of nm23-H1 and nm23-H2 transcripts in 149 patients with hematologic neoplasms, including 110 with de novo AML, 9 with de novo acute lymphoblastic leukemia, 14 with myelodysplastic syndrome, 16 with chronic myelogenous leukemia (CML), and 5 normal subjects by the reverse transcriptase-polymerase chain reaction. Expression of nm23-H1 was significantly higher in all the hematologic neoplasms, except CML in chronic phase, than in normal blood cells. nm23 may have a prognostic effect in these hematologic malignancies as well as in AML.

Acute Disease↗

The assessment of disease activity in rheumatoid arthritis using a multivariate analysis.

A simple method of assessing 'index of disease activity' (IDA) in rheumatoid arthritis (RA) using a multivariate analysis (MVA) comprising morning stiffness (MS), pain scale (PS), grip strength (GS), articular index (AI), haemoglobin (Hb) and erythrocyte sedimentation rate (ESR) is described. The IDA of 99 patients with RA was assessed using MVA. The method could be used reliably and readily for random or longitudinal assessment, in drug trials and for comparing disease activity with other objective indices.

Adult↗

Multivariate analysis of heavy metal contents in soils, sediments and water in the region of Meknes (central Morocco).

Concentrations of Al, Fe, Cr, Cu, Ni, Pb and Zn in soils, sediments and water samples collected along the Oued Boufekrane river (Meknes, central Morocco) were determined. In soils, a homogeneous distribution of metal concentrations was observed throughout the study area except for Pb, which presents high enrichment at sites located at the vicinity of a main highway. In sediments, high enrichment, with respect to upstream sites, were observed downstream of the city of Meknes for Al, Cr, Fe and Ni and inside the city for Cu, Zn and Pb. In water samples, the metal contents showed to correlate with their homologues in sediments suggesting that the metal contents in water and sediments have identical origins. Descriptive statistics and multivariate analysis (principal factor method, PFM) were used to assist the interpretation of elemental data. This allowed the determination of the correlations between the metals and the identification of three main factor loadings controlling the metal variability in soils and sediments.

Environmental Monitoring↗

Multivariate analysis of prognostic factors in 106 patients with malignant glioma.

The aim of this study was to evaluate the outcome and prognostic factors influencing survival in 106 patients with supratentorial malignant gliomas treated with radiotherapy. The study group included 84 patients treated by surgery and post-operative radiotherapy and 22 patients treated by postbiopsy irradiation. Radiotherapy was delivered to the tumour area with a 2 cm margin, the aimed curative dose was 60 Gy in 6-7 weeks. The 60-month overall survival (Kaplan-Meier) was 20%. Following a univariate analysis, younger age (P < 0.001), longer duration of symptoms (P = 0.009), good performance status after radiotherapy (P < 0.001), other than grade 4 histology (P < 0.001) and higher radiation dose (P < 0.001) were associated with better overall survival rates. Multivariate analysis found that age, symptom duration, histology, extent of symptoms and radiation dose were independent prognostic factors influencing survival. In conclusion, conventional radiotherapy of supratentorial malignant gliomas results in survival that is comparable to results from clinical experiments with different fractionation schedules and radiation with chemotherapy or radiosensitisers. To improve the results, new approaches are needed, especially for patients with the poorest prognosis after standard treatment.

Adolescent↗

[Multivariate analysis on prognostic factors of non-Hodgkin's lymphoma].

OBJECTIVE: To predict the prognostic factors and to improve the response and survival in intermediate-grade and high-grade non-Hodgkin lymphoma (NHL). METHODS: 200 patients with intermediate-grade and high-grade NHL were treated with chemotherapy. A multivariate Cox model was used to analyse the prognostic factors that significantly affect the treatment outcome. The variables examined included: sex, age, clinic stage of disease, B symptoms, extranodal sites, bone marrow involvement, tumor bulk, performance status (ECOG) and malignancy grades. RESULTS: Multivariate analysis showed that performance status, the number of extranodal sites, pathologic malignancy grade and tumor bulk were significantly independent prognostic factors. These factors were put together to construct a prognostic index formula. The index partitioned the patients into low risk group (PI -2.43(-)-1.30), intermediate risk group (PI -1.29-1.0) and high risk group (PI > 1.0) giving 5-year survival rates of 76.0%, 21.6% and 7.4%, respectively. CONCLUSION: The prognostic index formula and subgroups could serve as a reference to distinguish patients requiring more intensive chemotherapy and autologous stem cell transplantation from those who should be treated with standard regimens in order to improve the prognosis.

Adolescent↗

Prognostic factors in differentiated thyroid carcinoma: a multivariate analysis of 234 consecutive patients.

BACKGROUND AND OBJECTIVES: The clinical characteristics and patient outcome of a group of patients treated for differentiated thyroid carcinoma (DTC) were analyzed in order to assess the relative influence of different prognostic factors. MATERIALS AND METHODS: We retrospectively reviewed data about sex, age, size and histologic behavior of the tumor, extrathyroid extension of the tumor, lymph node status, distant metastasis at diagnosis, surgical procedures, and overall survival from 234 patients treated for DTC. Data were submitted to a statistical analysis. RESULTS: Using a univariate analysis, we found that survival rates were significantly influenced by age (P = 0.0001), size (P = 0.018), extrathyroidal extension (P = 0.000001), lymph node involvement (P = 0.03), and distant metastases (P = 0.049). Age and size were independent prognostic factors at multivariate analysis (t = 2.694 and t = 2.443, respectively). CONCLUSIONS: On the basis of our results and of a review of the literature, we conclude that total thyroidectomy is the treatment of choice in DTC, except for small (<1 cm) papillary carcinoma, that could be treated by lobectomy plus isthmectomy, while lymphadenectomy is indicated only in case of macroscopic involvement.

Adolescent↗

A multivariate analysis of en bloc extended radical mastectomy versus conventional radical mastectomy in operable breast cancer.

We made clinical trials of en bloc extended radical mastectomy (EXT) of a new type in 118 patients from 1980 through 1985. A variety of conventional radical mastectomies (RDL) were also performed in 105 patients from 1973 through 1985. A multivariate analysis was performed of the results to compare EXT and RDL. The result showed the 5-year survival rates of 91 +/- 2.6% and 83 +/- 3.7% were achieved for the EXT and RDL groups, respectively (Cox P value for comparison of survival curves = 0.16). Adjusted Cox regression analysis revealed a significantly favourable result of EXT (P = 0.05). This difference was most remarkable in patients with one to three metastatic axillary lymph nodes, although it was not statistically significant because of too small a number of patients available (P = 0.18). The results are thus not definite, but suggest that EXT may be advantageous over RDL especially in patients with a few metastatic axillary lymph nodes.

Aged↗

Long-term risk factors for bleeding after first course of endoscopic injection sclerotherapy: a univariate and multivariate analysis.

The purpose of this study was to define the risk factors linked to the rupture of esophageal varices following endoscopic injection sclerotherapy. A total of 197 patients with esophageal varices who had been treated by endoscopic injection sclerotherapy between 1985 and 1991 were observed for post-therapeutic bleeding from esophageal varices. Among 197 patients, 96 had esophageal varices and concomitant hepatocellular carcinoma. Analysis by the multivariate Cox's proportional hazard model disclosed that incomplete eradication of esophageal varices, the presence of hepatocellular carcinoma, and Child-Pugh classes were statistically significant predictors for rupture of esophageal varices after sclerotherapy. We conclude that complete eradication of esophageal varices is essential for sustained effectiveness of endoscopic injection sclerotherapy. The presence of hepatocellular carcinoma and a lack of hepatic functional reserve, as indicated by Child's classification, are also major determinants of post-therapeutic bleeding.

Carcinoma, Hepatocellular↗

Multivariate analysis of factors predictive of brain metastases in localised non-small cell lung carcinoma.

Brain metastases are a frequent feature of the course of non-small cell lung carcinoma (NSCLC). The potential usefulness of prophylactic cranial irradiation (PCI) has led to the search for target groups likely to derive benefit. This multivariate analysis looked for factors predictive of brain metastases in a group of stages I-III NSCLC patients under care of the thoracic oncology unit of Besançon University Hospital from 1977 to 2001. All the patients had the same follow-up. They were divided into two groups: BM+ when they had a brain metastasis as the first site of progression, whether solitary or not, and BM(-) otherwise. Variables analysed were age, gender, performance status (0-1 versus 2-3), weight-loss stage T-status, N-status, pathological type, type of treatment, administration of chemotherapy, use of cisplatin and response to treatment. Three hundred and five patients were eligible and there were 77 patients (25.25%) in the BM+ group. Median time to onset of brain metastases was 12 months (1-163 months) and median survival from the diagnosis of brain metastases was 6 months (1-65 months). Factors predictive of brain progression were age < or =62 years (RR: 2.5, 95% CI: 1.33-4.76 and P = 0.004), T4 tumour status (RR: 3.75, 95% CI: 1.72-8.21 and P = 0.0009), N2-3 (RR: 2.61, 95% CI: 1.32-5.15 and P = 0.0057), and adenocarcinoma (RR: 3.39, 95% CI: 1.78-6.46 and P = 0.0002). No aspect of treatment plays a role in the frequency of this type of metastasis. These factors predictive of brain progression could serve as a basis for the selection of patients with the aim of sitting of studies on prophylactic cranial irradiation in NSCLC.

Adenocarcinoma↗

Prediction of extraprostatic extension of prostate cancer based on needle biopsy findings: perineural invasion lacks significance on multivariate analysis.

Extraprostatic extension (EPE) and seminal vesicle invasion (SVI) are adverse prognostic factors in prostate cancer, and their prediction before prostatectomy would be useful. Perineural invasion in needle biopsy has been advocated as a marker of extraprostatic extension, but its independent value as a predictor of stage has not been established. We studied 349 previously untreated men with prostatic adenocarcinoma who underwent bilateral pelvic lymphadenectomy and radical retropubic prostatectomy. All patients were clinically free of metastases and had cancer that was diagnosed on needle biopsy. Five preoperative variables were collected: clinical stage (TNM staging system), serum prostate-specific antigen (PSA), Gleason score on needle biopsy, presence or absence of perineural invasion, and proportion of the biopsy involved by cancer. The subsequent prostatectomy specimens were completely embedded, and whole mount sections were used to evaluate four outcome staging variables: EPE (absent/present), EPE (absent/unilateral/bilateral), seminal vesicle invasion, and pathologic stage (TNM). On univariate analysis, each preoperative variable was significantly associated with each outcome variable except for a lack of association between clinical stage and SVI. Perineural invasion in the biopsy predicted EPE with a sensitivity of 51%, specificity of 70%, positive predictive value of 49%, and negative predictive value of 71%. On multivariate analysis (stepwise logistic regression), only preoperative PSA, proportion of the biopsy involved by cancer, and Gleason score were significant (p < 0.05); perineural invasion and clinical stage had no independent predictive value for any of the outcome variables. We conclude that the finding of perineural invasion in needle biopsy of prostatic carcinoma has no independent predictive value for the presence of extraprostatic extension, seminal vesicle involvement, or pathologic stage in the radical prostatectomy. Accordingly, we no longer routinely evaluate this finding in biopsy specimens.

Adenocarcinoma↗

Multivariate analysis of prognostic factors in T3 N0 laryngeal carcinoma treated with total laryngectomy.

OBJECTIVE: The aim of our study was to clarify the real importance of 16 possible prognostic factors analyzed retrospectively for the disease-free interval and survival of a total of 327 patients with T3 N0 M0 laryngeal carcinoma treated with total laryngectomy. METHODS: The role of each possible prognostic factor and their joint effect was explored by Cox proportional hazard survival analysis. Results and conclusions In a Cox univariate analysis for the whole group, tumor site, pattern of growth, tumor size, histologic grading, lymph node status, and the occurrence of postoperative complications were predictive of the risk of tumor recurrence. In univariate analysis, all these factors except for pattern of tumor growth, neck treatment and postoperative complications maintained their prognostic value when analyzed as predictors of survival; however, the loco-regional control of disease was the most significant one. In a Cox multivariate analysis tumor size, histologic grading and postoperative complications had a significant impact on disease-free survival, whereas only histologic grading and loco-regional failure appeared to be prognostic with a significant decrease in overall survival.

Adult↗