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PubMed1992

Argyrophilic nucleolar organiser regions in transitional cell bladder tumours related to established prognostic factors, progression and independent prognostic value.

Paraffin-embedded archival biopsy specimens from 229 primary transitional cell carcinomas (TCCs) were stained with silver nitrate to demonstrate the nucleolar organiser regions (Ag-NORs). T3-T4 high grade tumours had higher Ag-NOR counts/nucleus than low grade superficial papillary tumours (p less than 0.001). Non-papillary tumours showed more Ag-NORs than papillary ones (p less than 0.001). Aneuploid tumours with high S phase fraction had more Ag-NORs than diploid tumours (p less than 0.001) and mitotic frequency was also related significantly to Ag-NOR count (p less than 0.001). SD of nuclear area and nuclear area as measured by planar morphometry correlated significantly to Ag-NOR count (p less than 0.001). Close to 60% of the total number of Ag-NORs/nucleus can be related to other quantitative variables. Ag-NORs predicted independently survival in Ta-T1 tumours (p = 0.016) whereas in the whole series Ag-NORs had no independent prognostic value.

Aneuploidy↗
PubMed1978

Six-month prognostic norms derived from studies of the Rorschach Prognostic Rating Scale.

The Rorschach Prognostic Rating Scale (RPRS) was introduced in 1951 by Klopfer. Kirkner, Wisham, and Baker. The predictions of Klopfer et al. are compared to the outcomes in four studies of the RPRS. The originalinterpretation is shown to predict higher percentages of success than revealed by the empirical studies. A second interpretation of the scale is proposed on the basis of the experimental data. This interpretation relates RPRS scores to the chance for substantial improvement within 30 weeks of once weekly therapy by client-centered, rational-emotive, desensitization, aversion, or traditional methods. For any given RPRS score, the chance for substantial improvement is approximately the same for every type of therapy, and increases as the RPRS score increases. The second interpretation is proposed in both tubular and algebraic forms as a stimulus to further research and clinical applications.

Humans↗
PubMed1992

Using Cox's proportional hazards model for prognostication in carcinoma of the upper aero-digestive tract.

One of the major short comings of the traditional TNM system is its limited potential for prognostication. With the development of multifactorial analysis techniques, such as Cox's proportional hazards model, it has become possible to simultaneously evaluate a large number of prognostic variables. Cox's model allows both the identification of prognostically relevant variables and the quantification of their prognostic influence. These characteristics make it a helpful tool for analysis as well as for prognostication. The goal of the present study was to develop a prognostic index for patients with carcinoma of the upper aero-digestive tract which makes use of all prognostically relevant variables. To accomplish this, the survival data of 800 patients with squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx were analyzed. Sixty-one variables were screened for prognostic significance; of these only 19 variables (including age, tumor location, T, N and M stages, resection margins, capsular invasion of nodal metastases, and treatment modality) were found to significantly correlate with prognosis. With the help of Cox's equation, a prognostic index (PI) was computed for every combination of prognostic factors. To test the proposed model, the prognostic index was applied to 120 patients with carcinoma of the oral cavity or oropharynx. A comparison of predicted and observed survival showed good overall correlation, although actual survival tended to be better than predicted.

Adult↗
PubMed1992

Syntactic structure analysis in invasive breast cancer: analysis of reproducibility, biologic background, and prognostic value.

The reproducibility, biologic background, and prognostic value of syntactic structure analysis were studied in a group of 94 patients with invasive primary breast cancer. Using an interactive digitizing video overlay system, the centers of malignant breast cancer nuclei were marked in the five (subjectively) most cellular fields of vision for each case at a final magnification of X1,200, and the corresponding minimum spanning tree was composed for each field. From each minimum spanning tree, 10 syntactic structure features were derived; subsequently, the mean, standard deviation, minimum, and maximum values of the five fields analyzed were calculated for further statistical analysis. Forty statistics thus were available for each case. The reproducibility of repeatedly measuring the same field (independent of nuclearity) and the same patient twice by the same or different observers was good for most of the syntactic structure features. When comparing the statistics of the syntactic structure features with other established prognosticators, correlations were found with (in this order) standard deviation and mean nuclear area (expressing nuclear differentiation), volume percentage epithelium (expressing architectural differentiation), and mitotic activity index. In univariate survival analysis several syntactic structure statistics yielded prognostic significance, the best being the maximum of the number of nuclei with two neighbors (P = .002; Mantel-Cox test, 12.4). Multivariate analysis revealed that syntactic structure features did not provide additional prognostic values with regard to each other. However, they did show additional prognostic values with regard to the multivariate prognostic index (currently one of the best prognosticators in breast cancer), which combines the mitotic activity index, lymph node status, and tumor size. Measurement of syntactic structure features could therefore contribute to an improved prediction of prognosis of breast cancer patients. In conclusion, syntactic structure analysis is a simple, fast, and highly reproducible technique that shows prognostic value in invasive breast cancer and also has important prognostic value with regard to the well-established and prognostically strong morphometric features. It seems to be a promising new method of analyzing tissue architecture in breast cancer and perhaps in many other tumors.

Breast Neoplasms↗
PubMed2026

Non-small cell lung cancer and tumor-educated platelets: screening of biomarkers and construction of a prognostic model.

BACKGROUND: Lung cancer is a leading cause of cancer-related mortality worldwide, emphasizing the urgent need for effective early detection strategies. Traditional Chinese medicine (TCM) provides a unique perspective on tumor pathogenesis, focusing on concepts such as "long-term stasis leading to accumulation". Tumor-educated platelets (TEPs) offer potential as biomarkers due to their ability to reflect cancer heterogeneity and facilitate less invasive diagnostic approaches. This study aims to identify TEP-related prognostic biomarkers for non-small cell lung cancer (NSCLC) and to construct and validate a multigene prognostic model by integrating platelet transcriptomic data with tumor tissue datasets. METHODS: We performed comprehensive analysis of gene expression datasets obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) repositories to characterize transcriptomic differences among lung cancer specimens, normal tissue samples, and TEPs. Using R software, we identified Differentially expressed genes (DEGs) and subsequently applied a multi-stage analytical pipeline to TEP-associated DEGs, incorporating univariate Cox proportional hazards regression, least absolute shrinkage and selection operator (LASSO) regression, multivariate Cox regression, and stepwise regression modeling to pinpoint genes with prognostic significance. These prognostically relevant genes served as the foundation for developing a risk stratification model. We computed individual risk scores across both training and validation cohorts, enabling patient stratification into high- and low-risk categories. Model robustness was assessed through internal cross-validation and external validation procedures, while predictive performance was quantified using risk calibration metrics and receiver operating characteristic (ROC) curve analysis. RESULTS: Through systematic bioinformatics screening, we identified a four-gene prognostic signature comprising NELL2, C4orf48, PRAM1, and KLHL35, which served as the foundation for developing our risk stratification algorithm. Rigorous internal cross-validation and external cohort validation substantiated the moderate predictive performance of this signature. Comprehensive clinicopathological correlation analysis revealed that elevated risk indices, advanced pathological staging (stage III-IV), increased primary tumor dimensions, regional lymph node metastasis, and distant organ dissemination each demonstrated statistically significant associations with diminished overall survival (OS) outcomes in lung cancer patients. The clinical nomogram exhibited acceptable calibration, with calibration plots showing reasonable concordance between predicted and observed survival probabilities across all time points. Discriminative capacity assessment via time-dependent ROC analysis yielded area under the curve (AUC) values consistently surpassing 0.6, confirming moderate prognostic discrimination. Furthermore, decision curve analysis (DCA) demonstrated that our integrated multi-gene model conferred potential net clinical benefit compared to individual prognostic variables across the full spectrum of clinically relevant threshold probabilities (0-1 range), thereby establishing its potential utility for risk-informed clinical decision-making. CONCLUSIONS: This study identified NELL2, C4orf48, PRAM1, and KLHL35 as candidate TEP-related prognostic biomarkers for non-small cell lung cancer (NSCLC). The developed prognostic model shows preliminary potential for patient stratification, but its clinical application, particularly as a platelet-based liquid biopsy tool, requires further validation in independent TEP-based cohorts.

Tumor-educated platelets (TEPs)↗
PubMed1990

Further evaluation of the prognostic value of morphometric and flow cytometric parameters in breast-cancer patients with long follow-up.

The added prognostic value of cellular DNA content compared with single and combined morphometric factors and classical parameters such as tumor size, nodal status, histologic grade and estrogen receptor (ER) content was investigated in 225 consecutive breast-cancer patients with long follow-up. Of all features investigated, the MPI (multivariate prognostic index) had the strongest prognostic value [Mantel-Cox (MC) = 48.2, p less than 0.00005]. The results further showed that neither age nor ER content had significant prognostic value, but the DNA index (DI) as a single parameter had (though weak) prognostic significance (MC = 5.9, p = 0.015); a similar result was obtained with the percentage of S-phase cells (MC = 6.1, p = 0.013). The DI had (restricted) additional prognostic value to the morphometric features (MPI plus DI Mantel-Cox 53.0, p less than 0.0001). The percentage of S-phase cells had no additional prognostic value over the MPI. On the other hand, the additional value of the DI over tumor size and nodal status was much more impressive (MC = 41.0 and 40.7), although it did not reach the prognostic significance of the MPI. Prediction of disease outcome with a linear combination of quantitative microscopical parameters of the primary tumor alone [MAI (mitotic activity index), DI and mean nuclear area] was very accurate, even without considering lymph-node status (MC 30.8, p less than 0.0005). Grade had no additional value to the MPI at all (p = 0.76). This could be especially important for lymph-node-negative patients in whom the prognostic value of the MPI and the MAI are confirmed.

Breast↗
PubMed1991

Prognostic value of morphometry and DNA flow-cytometry features of invasive breast cancers detected by population screening: comparison with control group of hospital patients.

Using the prognostic value of morphometric and flow-cytometric features, a group of patients with invasive breast cancers detected with population screening (PS, n = 70) has been evaluated and compared with a random control group in 2 hospitals (H group, n = 225) diagnosed in the same period. The results show that the PS patients had smaller tumors, less positive lymph nodes, better differentiated tumors with a lower mitotic activity index (MAI) and lower values of the morphometric prognostic index (MPI). Furthermore, the women more frequently had diploid tumors and tumors with small nuclei. The second purpose was to evaluate whether quantitative microscopical features, in comparison with other prognostic features such as size of primary tumor, nodal status and histologic grade, are as strong prognosticators in PS tumors as in H-detected breast cancers. In comparison with H tumors, morphometric and flow-cytometric features, as well as tumor size, had the same prognostic value for the PS tumors. In contrast, nodal status was not significant within the PS group, and the same phenomenon was found in a subgroup of H patients with similar sized tumors. Of all quantitative microscopical features (MPI, MAI, mean nuclear area (MNA) and DNA Index (DI], the MAI had the strongest prognostic value. DI showed additional prognostic value to the MAI for patients with small tumors and with small tumor-cell nuclei, because a diploid pattern in these cases (this combination occurred in 21 patients of the total group = 30%) was correlated with a 95% 10-year survival rate. Histologic grade, although significant within the large H group, was of no prognostic value within the PS group, and also not as in the H sub-group with small tumors. It is concluded from morphometric and DNA flow-cytometric criteria that these prognostic features in invasive breast cancers detected by PS were all more favorable than in randomly detected hospital breast cancers. This may account for the reported better survival rate of PS patients. Furthermore, the prognosis of patients with small invasive breast cancers detected by population screening can be more accurately deduced by quantitative microscopical features than by axillary-lymph-node status.

Aged↗
PubMed1992

The changing importance of prognostic factors in breast cancer during long-term follow-up.

A cohort of 464 breast-cancer patients were followed up for over 10 years and the clinical, histological and morphometric factors were related to survival within different time periods during follow-up. Tumor diameter, axillary lymph-node status (pN), tubule formation and the fraction of intraductal growth as determined from the primary tumor biopsy specimen had prognostic value up to 5 years. Histological grade, morphometric nuclear factors and the M/V index had only short-term prognostic value immediately after the primary therapy. In axillary lymph-node-negative (ANN) tumors tubule formation, intraductal growth, tumor necrosis and tumor diameter had prognostic value during the first 3 postoperative years. In axillary lymph-node-positive (ANP) tumors, tumor diameter, intraductal growth and tubule formation had long-term prognostic value whereas the M/V index had prognostic value only for 1 postoperative year. Tumor diameter, axillary lymph-node status, tubule formation and the proportion of intraductal growth also had independent long-term prognostic value in a multivariate analysis and accordingly these factors can categorize breast-cancer patients into prognostic groups after several years of follow-up. In contrast, mitotic frequency loses its prognostic power within 2 postoperative years, while morphometric nuclear factors and histological grade have no practical prognostic value after 1 year of follow-up.

Breast Neoplasms↗
PubMed1992

Aminopyrine breath test in the prognostic evaluation of patients with cirrhosis.

This prospective study assessed the role of aminopyrine breath test in the prognosis of patients with cirrhosis, and evaluated whether the test provided useful information not included in the Pugh score. During a period of 36 months, 125 patients with biopsy proven liver cirrhosis were included, and followed for up to 48 months (median 17 months). During follow up 43 patients died (20 of liver failure). Survival was univariately related to aminopyrine breath test (p less than 0.02), Pugh score (p less than 0.01), presence of ascites (p less than 0.01), and sex (p less than 0.05). Using Cox's regression analysis, Pugh score, aminopyrine breath test, and sex, were independent significant predictors of survival. From the Cox's model a prognostic index was computed. According to a receiver operating characteristic curve analysis, the prognostic index predicting death showed an improvement in area under the curve when compared with a prognostic index calculated excluding aminopyrine breath test, but the improvement did not reach statistical significance (p = 0.12). A similar prognostic index was calculated to predict death from liver failure. Cox's regression analysis selected aminopyrine breath test, Pugh score, and aetiology as the best set of predictor covariates. According to a receiver operating characteristic curve analysis, a prognostic index cut off value of 2.6 had a 94% sensitivity and a 88% specificity. The prognostic index significantly improved prognostic accuracy when compared with a prognostic index calculated from Pugh score and aetiology, but excluding aminopyrine breath test (p = 0.05). These data disclose that the aminopyrine breath test offers additional prognostic information to the Pugh score, and the prognosis of patients with cirrhosis.

Adult↗
PubMed2026

Development and internal validation of a six-gene prognostic model based on galactose metabolism for overall survival in lung adenocarcinoma.

BACKGROUND: Lung cancer remains a leading cause of cancer incidence and mortality globally. Metabolic reprogramming promotes tumor progression and shapes an immunosuppressive tumor microenvironment. Galactose metabolism is involved in multiple malignancies, but its prognostic value in lung adenocarcinoma (LUAD) remains unclear. This study aimed to develop and internally validate a galactose metabolism-related multigene prognostic model for LUAD. METHODS: A retrospective prognostic model development and internal validation study was performed using RNA sequencing (RNA-seq) and clinical data from 585 LUAD patients in The Cancer Genome Atlas (TCGA). Differential expression, functional enrichment, univariate and multivariate Cox regression were applied to construct a prognostic gene signature. Internal validation was performed using bootstrap resampling. Model performance was evaluated by time-dependent receiver operating characteristic (ROC), C-index, calibration, and Kaplan-Meier analysis. Associations between the model and immune infiltration, immunotherapy responsiveness, and tumor stemness were also analyzed. RESULTS: A six-gene prognostic model (GALT, GANC, PGM1, GALM, B4GALT1, PGM2) was developed. The model showed good discrimination with 1-, 3-, and 5-year area under the curve (AUC) values of 0.719, 0.693, and 0.684, respectively. The low-risk group exhibited significantly longer survival, increased antitumor immune infiltration (CD8+ T cells, M1 macrophages, activated CD4+ memory T cells), higher expression of T cell proliferation-related genes, lower immune checkpoint expression, better predicted immunotherapy response, and lower tumor stemness compared with the high-risk group. CONCLUSIONS: We developed and internally validated a six-gene prognostic model for LUAD based on galactose metabolism. The model shows moderate prognostic performance and is associated with antitumor immunity and tumor stemness. It may be used for prognostic risk stratification and to guide personalized immunotherapy in LUAD.

Galactose metabolism↗
PubMed1990

Proposal for a simple synthesis prognostic staging system in chronic myelogenous leukemia.

PURPOSE: Several prognostic models or staging systems have been published that identify different risk groups in patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML). The aims of this study were (1) to test, in an independent population, the prognostic reproducibility of these staging systems; and (2) to develop a synthesis staging system that could be easily applied in clinical practice. PATIENTS AND METHODS: A total of 406 patients with newly diagnosed Ph-positive CML were evaluated by the four published staging systems of Tura, Cervantes, Sokal, and our group. The proposed synthesis staging system was developed based on the most consistent prognostic characteristics, and the presence or absence of accelerated disease features at diagnosis. The staging systems were compared according to survival outcome, as well as by looking for differences of survival outcomes within a specific stage of a defined system, when patients in this stage were subclassified by a second staging system. RESULTS: Whereas the staging system of Cervantes et al identified only two prognostic groups (median survivals of 49 versus 40 months; p = 0.01), the remaining three staging systems were able to segregate patients into stage 1, 2, and 3 risk groups with respective median survivals of 56 to 57, 41 to 42, and 28 to 36 months, respectively (p less than 0.001 to p less than 0.002). The new proposed staging system, based on the existence of zero to one (stage 1), two (stage 2), or three or more unfavorable (stage 3) characteristics, or the presence of accelerated disease features (stage 4), categorized patients into four prognostic groups with median survivals of 56, 45, 30, and 30 months, respectively (p less than 0.001), the latter stage (stage 4) being associated with a higher one-year mortality rate (29%). The synthesis staging system was also able to subclassify patients within most of Tura's and Sokal's stages into significantly different prognostic groups by survival outcome. CONCLUSION: The predictive prognostic capacity of three of the four published staging systems was confirmed in this independent or test population. The new proposed staging system was superior to the staging systems of Tura and Sokal in identifying different prognostic subgroups.

Humans↗
PubMed1991

Prognosis of transitional cell bladder cancer: a multivariate prognostic score for improved prediction.

Clinical and histological prognostic factors were evaluated by means of Cox's analysis in 265 bladder cancer patients with a mean followup of 10 years. The parameters studied were obtained from the primary biopsies, which included clinical stage, World Health Organization grade, papillary status, morphometrically measured mean nuclear area, standard deviation of nuclear area, mean nuclear area of the 10 largest nuclei, mitotic activity index and volume corrected mitotic index. In univariate survival analysis all of the parameters predicted survival (p less than 0.001). In Cox's analysis the clinical stage was the most important prognosticator (p less than 0.001) followed by papillary status (p less than 0.001), volume corrected mitotic index (p = 0.011) and nuclear area of the 10 largest nuclei (p = 0.091). In stages Ta to T2, grades 1 to 2 tumors the papillary status (p = 0.001), mitotic activity index (p = 0.021) and T category (p = 0.029) showed independent prognostic value. Among the stages Ta to T1 tumors the papillary status included all of the available prognostic information (p = 0.001). In a separate analysis of histological features in all papillary tumors histological grade (p less than 0.001) and mitotic activity index (p = 0.021) were related independently to survival in Cox's analysis. In papillary stages Ta to T2, grades 1 to 2 tumors (mitotic activity index, p = 0.029) and in papillary stages Ta to T1 tumors (volume corrected mitotic index, p = 0.054) mitotic indexes showed independent prognostic value. In grade 2 tumors the papillary status p = 0.004) and mitotic activity index (p = 0.090) had independent prognostic value. The mitotic indexes predicted progression among stages Ta to T1 tumors (p less than 0.001) and within World Health Organization grades significantly. The combination of prognostic parameters into prognostic scores gave a more accurate estimate of survival than the single parameter approach. The results suggest morphometric grading of bladder tumors. However, papillary and nonpapillary tumors require different grade limits.

Aged↗
PubMed1988

Limited prognostic value of cellular DNA content to classical and morphometrical parameters in invasive ductal breast cancer.

This retrospective study evaluates several prognostic factors in 63 patients with invasive ductal breast cancer. Special attention is paid to the additional prognostic value of cellular DNA content to the previously developed and evaluated quantitative features mitotic activity index (MAI) and multivariate morphometric prognostic index (MPI). Follow-up was monitored for at least 50 months (median survival, 78 months) and only patients who died of distant metastases were included. The results show that the MAI is the strongest prognostic factor of all single features (Mantel-Cox, P = 0.008). Although patients with a diploid or tetraploid tumor tended to have a better prognosis than those with an aneuploid cancer, the DNA index as a single parameter was a weak prognosticator in the univariate survival analysis (Mantel-Cox, P = 0.24). Within the diploid and tetraploid tumors the MAI could distinguish patients with a favorable and unfavorable prognosis prediction (chi-square, P = 0.01). For aneuploid tumors this was not possible. Analysis of combined features revealed that the MPI has a high prognostic value (Mantel-Cox, P = 0.0015), thus confirming other studies. A linear combination of the nuclear DNA index, MAI, nodal status, and mean nuclear area showed only a slight improvement in prognosis prediction compared with the MPI (Mantel-Cox, P = 0.0005); with this rule, the classification of the patients was more in agreement with the actual outcome in 4% of the cases. The gain was in the poor prognosis group. These results suggest that the additional prognostic value of nuclear DNA content is restricted when compared with the morphometric prognostic factors. Further studies on a larger number of patients are required to confirm these findings.

Breast Neoplasms↗