DigitalUM :: Browsing by Subject "Prognosis"

Browsing by Subject "Prognosis"

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Open Access
A comparative clinicopathological and survival analysis of synchronous bilateral breast cancers
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Bai, Yan; Lu, Junliang; Wu, Huanwen; Wang, Jing; Niu, Yiru; Pang, Junyi; Wu, Shafei; Liu, Yuanyuan; Liang, Zhiyong
Objective. The present study aimed to explore the clinicopathological characteristics, potential heterogeneity and prognostic factors in synchronous bilateral breast cancer (SBBC). Methods. We performed a retrospective review and paired comparison of the clinicopathological characteristics of 114 patients with SBBC in the Peking Union Medical College Hospital from January 2008 to September 2019. The prognostic significance of triple negativity status and coexistence ductal carcinoma in situ (DCIS) with bilateral invasive ductal carcinomas of no special type (IDC-NST) was analyzed in SBBC. Results. Most bilateral lesions on both sides were of IDC-NST, grade 2, luminal subtype, and stage I. Although most lesions were concordant between the left and right side, discordances were observed in histological type (25 cases, 21.9%), histological grade (31 cases, 27.2%), pTNM (61 cases, 53.5%), molecular subtypes (20 cases, 17.5%), and immunohistochemical staining of ER (18 cases, 15.8%), PR (26 cases, 22.8%), and HER2 (12 cases, 10.5%). Moreover, there was no significant difference in disease-free survival (DFS) and overall survival (OS) between IDC-NST with coexisting DCIS on both sides and IDC-NST with coexisting DCIS on one side or pure IDC-NST. SBBC with triple negativity on both sides exhibited a significantly shorter DFS and OS when compared with triple negativity on one side or non-triple negativity on both sides (p<0.001), and remained an independent prognostic factor by multivariate analysis. Conclusions. A considerable proportion of discordance in clinicopathological characteristics is observed in SBBC, supporting the necessity of comprehensive pathological examination including immunohistochemical testing on both sides in clinical practice. Moreover, SBBC with triple negativity on both sides is a prognostic for poor survival.
Open Access
A low nuclear-to-cytoplasmic ratio of VDR expression is an independent prognostic marker in breast cancer
(Universidad de Murcia, Departamento de Histología e Histopatología, 2025) Schubert Charlotte; Vilsmaier Theresa; Batz Falk; Cavaillès Vincent; Sixou Sophie; Kolben Thomas; Meister Sarah; Buschmann Christina; Hagemann Friederike; Biología Celular e Histología
The aim of this retrospective study was to analyze the prognostic value of cytoplasmic versus nuclear expression of the vitamin D receptor (VDR) in breast cancer (BC) tissue samples and to relate the results to clinicopathological parameters. VDR expression was assessed in 319 primary breast cancer patients using the Remmele and Stegner immunoreactive scoring (IRS) system. Follow-up data were obtained from the Munich Cancer Registry. The correlation with overall survival (OS) and disease-free survival (DFS) was calculated using univariate and multivariate analyses. Correlation analysis revealed a correlation between nuclear VDR expression and improved outcomes for both OS (p=0.004) and DFS (p=0.001). Conversely, cytoplasmic VDR expression was significantly associated with a shorter OS (p=0.003) and DFS (p<0.001). Additionally, both cytoplasmic and nuclear VDR expression were found to be independent markers of DFS (p<0.001; p=0.021) when examined alongside clinicopathological parameters. Moreover, nuclear VDR expression was positively associated with lower lymph node invasion (pN; p=0.01). For triple-negative patients, cytoplasmic VDR expression was found to have a significant inverse correlation with DFS (p<0.001). Lastly, the ratio of VDR nuclear/cytoplasmic was identified as an auxiliary independent marker of DFS and OS. These findings strongly indicate that the subcellular localization of VDR is crucial in determining BC prognosis. The expression of nuclear VDR appears to have a protective effect, while cytoplasmic VDR is associated with a more aggressive disease course. The data may help identify subgroups of patients with high-risk BC, possibly leading to specific options for targeted tumor therapy
Open Access
A predictive model for hospitalization and survival to COVID‑19 in a retrospective population‑based study
(Nature Research, 2022-10-28) Cisterna García, Alejandro; Guillén Teruel, Antonio; Caracena, Marcos; Pérez-Cuadrado Martínez, Enrique; Jiménez Barrionuevo, Fernando; Francisco Verdú, Francisco J.; Reina, Gabriel; González Billalabeitia, Enrique; Palma Méndez, José Tomás; Sánchez Ferrer, Álvaro; Botía Blaya, Juan Antonio; Ingeniería de la Información y las Comunicaciones; Facultades de la UMU::Facultad de Informática
The development of tools that provide early triage of COVID-19 patients with minimal use of diagnostic tests, based on easily accessible data, can be of vital importance in reducing COVID-19 mortality rates during high-incidence scenarios. This work proposes a machine learning model to predict mortality and risk of hospitalization using both 2 simple demographic features and 19 comorbidities obtained from 86,867 electronic medical records of COVID-19 patients, and a new method (LR-IPIP) designed to deal with data imbalance problems. The model was able to predict with high accuracy (90–93%, ROC-AUC = 0.94) the patient's final status (deceased or discharged), while its accuracy was medium (71–73%, ROC-AUC = 0.75) with respect to the risk of hospitalization. The most relevant characteristics for these models were age, sex, number of comorbidities, osteoarthritis, obesity, depression, and renal failure. Finally, to facilitate its use by clinicians, a user-friendly website has been developed (https://alejandrocisterna.shinyapps.io/PROVIA).
Open Access
A redefinition of prognosis: Invasive carcinoma with metastasis originating from microglandular adenosis
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2026) Xiaochun Fei; Dan Chen; Biología Celular e Histología
Aim. To investigate the clinicopathological features, immunophenotype, diagnosis, and prognosis of invasive carcinoma originating from microglandular adenosis. Methods. Two cases of invasive carcinoma originating from microadenosis were analyzed in the Department of Pathology of the Ruijin Hospital affiliated with the Medical College of Shanghai Jiaotong University. Histopathological morphology, immuno-histochemical staining, and prognosis were observed. Results. (1) Histopathological morphology: microscopically, the tumor showed small clusters and nests of infiltrative growth; a few areas showed tubules, and some eosinophilic secretions were observed in the lumen. (2) Immunohistochemistry and molecular genetics: Case 1 was partly positive for S-100, positive for SOX-10, and negative for ER, PR, and HER2 (2+). The result of HER2 gene amplification was negative. Breast and liver tissue lesions in Case 2 were positive for S-100 and SOX-10 but negative for ER and HER2. PR was positive in the liver lesions but showed moderate to strong expression in approximately 80% of the staining. Myoepithelial markers (p63 and calponin) showed loss of myoepithelium around the nests of invasive cancers. TP53 (R213Ter) showed somatic gene variations, and no exon amplification or deletion was detected in BRCA1/2. Conclusion. Invasive carcinoma originating from microadenosis has the same immunophenotype as microadenosis, and its prognosis is difficult to determine.
Open Access
A toolbox of lectins for translating the sugar code: the galectin network in phylogenesis and tumors
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2012) Kaltner, Herbert; Gabius, Hans-Joachim
Lectin histochemistry has revealed cell-type-selective glycosylation. It is under dynamic and spatially controlled regulation. Since their chemical properties allow carbohydrates to reach unsurpassed structural diversity in oligomers, they are ideal for high density information coding. Consequently, the concept of the sugar code assigns a functional dimension to the glycans of cellular glycoconjugates. Indeed, multifarious cell processes depend on specific recognition of glycans by their receptors (lectins), which translate the sugar-encoded information into effects. Duplication of ancestral genes and the following divergence of sequences account for the evolutionary dynamics in lectin families. Differences in gene number can even appear among closely related species. The adhesion/growth-regulatory galectins are selected as an instructive example to trace the phylogenetic diversification in several animals, most of them popular models in developmental and tumor biology. Chicken galectins are identified as a low-level-complexity set, thus singled out for further detailed analysis. The various operative means for establishing protein diversity among the chicken galectins are delineated, and individual characteristics in expression profiles discerned. To apply this galectin-fingerprinting approach in histopathology has potential for refining differential diagnosis and for obtaining prognostic assessments. On the grounds of in vitro work with tumor cells a strategically orchestrated co-regulation of galectin expression with presentation of cognate glycans is detected. This coordination epitomizes the far-reaching physiological significance of sugar coding
Open Access
A useful immunohistochemical approach to evaluate intraductal proliferative lesions of the breast and to predict their prognosis
(Murcia: F. Hernández, 2011) Omi, Yoko; Yamamoto, Tomoko; Okamoto, Takahiro; Obara, Takao; Kobayashi, Makio
An examination was performed on 16 intraductal proliferative breast lesions diagnosed as intraductal papillomas (IP) or usual ductal hyperplasia (UDH), which were followed up for more than 3 years. An immunohistochemical marker panel combining myoepithelial markers, high-molecular-weight keratin (HMWK) and neuroendocrine markers was used. Two of 11 IP cases were re-evaluated as atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS). These cases developed breast cancer after the first operation. One IP case showed repeated recurrences. None of the other IP and UDH cases had breast cancer or recurrence. The ADH, DCIS and the recurrent IP showing a solid growth lacked myoepithelia, but the recurrent IP expressed HMWK, immunohistochemically. Interestingly, these three lesions were weakly positive for neuroendocrine markers. All other IPs and UDHs, including lesions having solid components, were negative for neuroendocrine markers, and most of them were positive for myoepithelial markers and/or HMWK. A combination of the above immunohistochemical markers seems useful to evaluate intraductal proliferative lesions and to predict their prognosis. In particular, intraductal proliferative lesions with solid components exhibiting positivity for neuroendocrine markers should be followed up carefully to monitor breast cancer risk or recurrence.
Open Access
Abnormal expression and clinicopathologic significance of p120-catenin in lung cancer
(Murcia : F. Hernández, 2006) Wang, E.H.; Liu, Y.; Xu, H.T.; Dai, S.D.; Liu, N.; Xie, C.Y.; Yuan, X.M.
Summary. The aim of this study was to investigate the relationship between the expression of p120ctn in human lung squamous cell carcinoma, adenocarcinoma and its clinicopathologic significance. The expression of p120ctn in tumors and adjacent normal lung tissues from 143 patients was examined by immunohistochemistry and Western blot. Expression of p120ctn occurs mainly in the cell membrane of normal bronchial mucosa. Abnormal expression of p120ctn, including cytoplasmic and reduced membranous expression, was found in 114 of 143 specimens (79.7%) and was significantly associated with poor differentiation, high TNM stage, and lymph node metastasis (P<0.05 for each) but not with histologic subtype. The Kaplan-Meier survival test revealed that abnormal expression of p120ctn was related to poor survival (P<0.001). A Cox regression analysis revealed that abnormal p120ctn expression was an independent factor in predicting patient survival (P=0.024). Compared with that in normal lung tissues, membranous protein level was lower in tumors (P=0.003). Abnormal expression of p120ctn is associated with tumor progression and poor prognosis in lung squamous cell carcinoma and adenocarcinoma. Reduced expression or even the absence of p120ctn isoform 1 and 3 in tumor cell membranes may be responsible for the abnormal expression of p120ctn that has been found in lung cancer.
Open Access
Abnormal p16 expression and prognostic significance in esophageal squamous cell carcinoma
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Jiang, Dongxian; Zhang, Xue; Chen, Weijie; Peng, Rui; Zhang, Xiaolei; Gao, Feng; Huang, Yufeng; Gu, Wenyi; Hou, Yingyong
Background. The purpose of this study was to analyze p16 expression status and evaluate whether abnormal p16 expression was associated with prognosis in a large-scale esophageal squamous cell carcinoma (ESCC) cohort of patients. Methods. We retrospectively evaluated p16 expression status of 525 ESCC samples using immunohistochemistry. Associations between abnormal p16 expression and survival were analyzed. Results. P16 negative, focal expression and overexpression were found in 87.6%, 6.9% and 5.5% of ESCC patients. No significant association was observed between abnormal p16 expression and age, sex, tumor site and location, differentiation, vessel and nerve invasion, T stage and lymph node metastasis. In all patients, the survival of p16 focal expression group tended to be better compared with negative group (disease free survival/DFS P=0.040 and overall survival/OS P=0.052) and overexpression group (DFS P=0.201 and OS P=0.258), and there was no survival difference between negative group and overexpression group. The multivariate analysis for OS and DFS found that only clinical stage was a significantly independent prognostic factor (P<0.001). When patients were divided into I-II stage (n=290) and III-IVa stage (n=235), the survival of focal expression group was better compared with negative group (DFS P=0.015 and OS P=0.019), and tended to be better compared with overexpression group (DFS P=0.405 and OS P=0.432) in I-II stage ESCC, which was not found in III-IVa stage ESCC. Conclusion. P16 overexpression or negative expression tend to be associated with unfavorable outcomes, especially in I-II stage ESCC. Our study will help to identify a subgroup of ESCC patients with excellent prognosis after surgical therapy
Open Access
APOBEC3B protein expression and mRNA analyses in patients with high-grade serous ovarian carcinoma
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Rüder, Ulrike; Denkert, Carsten; Alisa Kunze, Catarina; Jank, Paul; Lindner, Judith; Jöhrens, Korinna; Kulbe, Hagen; Sehouli, Jalid; Dietel, Manfred; Braicu, Elena; Darb Esfahani, Silvia
APOBEC3 enzymes are part of the innate immune system and they are important in retroviral defense. The number of mutations in ovarian cancer increases with rising levels of APOBEC3B mRNA. We could confirm that APOBEC3B mRNA is upregulated in ovarian cancer cell lines and in ovarian cancer tissue. We evaluated APOBEC3B expression in histologically defined subtypes of ovarian cancer to identify its influence on overall survival (OS) and progression-free survival (PFS). Tissue microarrays from 219 patients with highgrade serous (HGSC), 61 with low-grade serous (LGSC), 62 with endometrioid (EC) and 55 with clear cell (CCC) ovarian carcinoma were stained using an antibody against APOBEC3B. Real-time quantitative PCR was performed to detect APOBEC3B mRNA levels in 274 cases of HGSC, in 11 cases of LGSC, in 47 cases of EC and in 29 cases of CCC. Tumor-infiltrating lymphocytes (TILs) have been evaluated in a previous project. APOBEC3B staining was cytoplasmic as well as nuclear and both were positively correlated (P<0.001). In HGSC a trend was detectable for positive cytoplasmic staining as favorable regarding OS (P=0.283) and PFS (P=0.137). High levels of APOBEC3B mRNA were associated with prolonged PFS in HGSC in univariate analyses (P=0.043) and multivariate analyses (HR 0.55; 95% CI 0.35-0.88; P=0.012). APOBEC3B cytoplasmic staining and APOBEC3B mRNA were positively correlated with TILs. APOBEC3B in HGSC is related to an active immune infiltrate. However, there is no evidence for APOBEC3B as a clinically relevant prognostic biomarker.
Open Access
Association of body mass index with clinical outcomes in patients with atrial fibrillation: a report from the FANTASIIA registry
Bertomeu-Gonzalez, Vicente; Moreno-Arribas, José; Esteve-Pastor, María Asunción; Roldan-Rabadán, Inmaculada; Muñiz, Javier; Raña-Miguez, Paula; Ruiz-Ortiz, Martín; Cequier, Ángel; Bertomeu-Martinez, Vicente; Badimón, Lina; Anguita, Manuel; Lip, Gregory Y.H.; Marin Ortuño, Francisco; Medicina
Background-—Obesity and atrial fibrillation (AF) frequently coexist and independently increase mortality. We sought to assess the association between obesity and adverse events in patients receiving oral anticoagulants for AF. Methods and Results-—Consecutive AF outpatients receiving anticoagulant agents (both vitamin K antagonists and direct oral anticoagulants) were recruited into the FANTASIIA (Atrial fibrillation: influence of the level and type of anticoagulation on the incidence of ischemic and hemorrhagic stroke) registry. This observational, multicenter, and prospective registry of AF patients analyzes the quality of anticoagulation, incidence of events, and differences between oral anticoagulant therapies. We analyzed baseline patient characteristics according to body mass index, normal: <25 kg/m2, overweight: 25–30 kg/m2, and obese: ≥30 kg/m2), assessing allcause mortality, stroke, major bleeding and major adverse cardiovascular events (a composite of ischemic stroke, myocardial infarction, and total mortality) at 3 years’ follow-up. In this secondary prespecified substudy, the association of weight on prognosis was evaluated. We recruited 1956 patients (56% men, mean age 73.8 9.4 years): 358 (18.3%) had normal body mass index, 871(44.5%) were overweight, and 727 (37.2%) were obese. Obese patients were younger (P<0.01) and had more comorbidities. Mean time in the therapeutic range was similar across body mass index categories (P=0.42). After a median follow-up of 1070 days, 255 patients died (13%), 45 had a stroke (2.3%), 146 a major bleeding episode (7.5%) and 168 a major adverse ardiovascular event (8.6%). Event rates were similar between groups for total mortality (P=0.29), stroke (P=0.90), major bleeding (P=0.31), and major adverse cardiovascular events (P=0.24). On multivariate Cox analysis, body mass index was not independently associated with all-cause mortality, cardiovascular mortality, stroke, major bleeding, or major adverse cardiovascular events. Conclusions-—In this prospective cohort of patients anticoagulated for AF, obesity was highly prevalent and was associated with more comorbidities, but not with poor prognosis.
Open Access
Association of low angiomotin-p130 and high YAP1 nuclear expression with adverse prognosis in epithelial ovarian cancer
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Cai, Junna; Han, Xiaorui; Li, Meng; Liu, Xiaoli; Zhang, Fengying; Wu, Xiaohua
Objectives. The aim of our study was to examine the association of Angiomotin (Amot-p130) and Yes-associated protein 1 (YAP1) expressions and their prognostic significance in epithelial ovarian cancer (EOC). Methods. A total of 100 primary EOC samples were obtained for immunohistochemical analysis of Amot-p130 and YAP1 expressions. Correlation analysis was performed between Amot-p130 or YAP1 and clinical factors. The overall survival time was calculated. Results. Low Amot-p130 and high YAP1 nuclear expression were identified in 34 and 56 of 100 EOC tissues, respectively. Both low Amot-p130 and high YAP1 nuclear expression were associated with advanced tumor stage, high-grade carcinoma, and non-response to chemotherapy (p<0.05). They were also associated with shorter overall survival time (p<0.05) by log-rank test. A marker of low Amot-p130 and high YAP1 expression was associated with high-grade ovarian carcinoma, late-stage disease, non-response to chemotherapy, and shorter overall survival time (p<0.05). Conclusions. Low Amot-p130 and high YAP1 nuclear expression can provide additional prognostic information for patients with EOC. A marker of low Amot-p130 and high YAP1 expression may be a potent predictor of poor prognosis in patients with epithelial ovarian cancer.
Open Access
Biomarkers of squamous cell carcinoma of the head and neck
(Murcia : F. Hernández, 1997) Kim, J.B.; Shin, D.M.
Despite the remarkable advances in cancer treatment, the 5-year survival rate for head and neck squamous cell carcinoma (HNSCC) has improved only marginally over the past 20 years. Investigators have attempted to develop new therapeutic methods to improve the survival rate from these tumors. Another approach, chemoprevention, has recently been tried to reduce cancer incidence. Biological understanding of tumorigenesis is critically important to provide risk assessment and intermediate end points during chemoprevention trials. Based on the fact that HNSCC develops through a multistep process by the accumulation of genetic and phenotypic changes in the field exposed to carcinogens, the investigation of specific biomarkers that represent each step must be valuable, since these biomarkers could be used to inhibit andlor to reverse the pathway of carcinogenesis. The potential biomarkers are classified as nonspecific and specific genetic biomarkers, proliferation markers, and differentiation markers in this review. Their usefulness in predicting tumors' biological behavior and responses to treatment and in monitoring the preventive effects of chemoprevention trials is also discussed.
Open Access
Cancer Survival in Adults in Spain: A Population-Based Study of the Spanish Network of Cancer Registries (REDECAN)
(MDPI, 2022-05-15) Guevara, M; Molinuevo, A; Marcos-Gragera, R; Carulla, M; Rodríguez Camblor M; Alemán, A; Rojas, D; Vizcaíno Batllés, A; Chico, M; Jiménez Chillarón, R; López de Munain, A; de Castro, V; Sánchez, MJ; Ramalle-Gómara, E; Franch, P; Galceran, J; Ardanaz, E; Chirlaque López, María Dolores; Salmerón Martínez, Diego; Ciencias Sociosanitarias
The assessment of cancer survival at the population level is essential for monitoring progress in cancer control. We aimed to assess cancer survival and its trends in adults in Spain. Individual records of 601,250 adults with primary cancer diagnosed during 2002-2013 and followed up to 2015 were included from 13 population-based cancer registries. We estimated net survival up to five years after diagnosis and analyzed absolute changes between 2002-2007 and 2008-2013. Estimates were age-standardized. Analyses were performed for 29 cancer groups, by age and sex. Overall, age-standardized five-year net survival was higher in women (61.7%, 95% CI 61.4-62.1%) than in men (55.3%, 95% CI 55.0-55.6%), and ranged by cancer from 7.2% (pancreas) to 89.6% (prostate) in men, and from 10.0% (pancreas) to 93.1% (thyroid) in women in the last period. Survival declined with age, showing different patterns by cancer. Between both periods, age-standardized five-year net survival increased overall by 3.3% (95% CI 3.0-3.7%) in men and 2.5% (95% CI 2.0-3.0%) in women, and for most cancer groups. Improvements were greater in patients younger than 75 years than in older patients. Chronic myeloid leukemia and myeloma showed the largest increases. Among the most common malignancies, the greatest absolute increases in survival were observed for colon (5.0%, 95% CI 4.0-6.0%) and rectal cancers (4.5%, 95% CI 3.2-5.9%). Survival improved even for some cancers with poor prognosis (pancreas, esophagus, lung, liver, and brain cancer). Further investigation of possible sociodemographic inequalities is warranted. This study contributes to the evaluation of cancer control and health services' effectiveness.
Open Access
Cardiopulmonary Exercise test in patients with hypertrophic cardiomyopathy: a systematic review and meta-analysis
(MDPI, 2021-05-25) Bayonas Ruiz, Adrián; Muñoz Franco, Francisca M.; Ferrer Pérez, Vicente; Pérez Caballero, Carlos; Sabater Molina, María; Tomé Esteban, María Teresa; Bonacasa Fernández, Bárbara; Fisiología
Background: Patients with chronic diseases frequently adapt their lifestyles to their functional limitations. Functional capacity in Hypertrophic Cardiomyopathy (HCM) can be assessed by stress testing. We aim to review and analyze the available data from the literature on the value of Cardiopulmonary Exercise Test (CPET) in HCM. Objective measurements from CPET are used for evaluation of patient response to traditional and new developing therapeutic measurements. Methods: A systematic review of the literature was conducted in PubMed, Web of Science and Cochrane in Mar-20. The original search yielded 2628 results. One hundred and two full texts were read after the first screening, of which, 69 were included for qualitative synthesis. Relevant variables to be included in the review were set and 17 were selected, including comorbidities, body mass index (BMI), cardiac-related symptoms, echocardiographic variables, medications and outcomes. Results: Study sample consisted of 69 research articles, including 11,672 patients (48 ± 14 years old, 65.9%/34.1% men/women). Treadmill was the most common instrument employed (n = 37 studies), followed by upright cycle-ergometer (n = 16 studies). Mean maximal oxygen consumption (VO2max) was 22.3 ± 3.8 mL·kg−1·min−1. The highest average values were observed in supine and upright cycle-ergometer (25.3 ± 6.5 and 24.8 ± 9.1 mL·kg−1·min−1; respectively). Oxygen consumption in the anaerobic threshold (ATVO2) was reported in 18 publications. Left ventricular outflow tract gradient (LVOT) > 30 mmHg was present at baseline in 31.4% of cases. It increased to 49% during exercise. Proportion of abnormal blood pressure response (ABPRE) was higher in severe (>20 mm) vs. mild hypertrophy groups (17.9% vs. 13.6%, p < 0.001). Mean VO2max was not significantly different between severe vs. milder hypertrophy, or for obstructive vs. non-obstructive groups. Occurrence of arrhythmias during functional assessment was higher among younger adults (5.42% vs. 1.69% in older adults, p < 0.001). Twenty-three publications (9145 patients) evaluated the prognostic value of exercise capacity. There were 8.5% total deaths, 6.7% cardiovascular deaths, 3.0% sudden cardiac deaths (SCD), 1.2% heart failure death, 0.6% resuscitated cardiac arrests, 1.1% transplants, 2.6% implantable cardioverter defibrillator (ICD) therapies and 1.2 strokes (mean follow-up: 3.81 ± 2.77 years). VO2max, ATVO2, METs, % of age-gender predicted VO2max, % of age-gender predicted METs, ABPRE and ventricular arrhythmias were significantly associated with major outcomes individually. Mean VO2max was reduced in patients who reached the combined cardiovascular death outcome compared to those who survived (−6.20 mL·kg−1·min−1; CI 95%: −7.95, −4.46; p < 0.01). Conclusions: CPET is a valuable tool and can safely perform for assessment of physical functional capacity in patients with HCM. VO2max is the most common performance measurement evaluated in functional studies, showing higher values in those based on cycle-ergometer compared to treadmill. Subgroup analysis shows that exercise intolerance seems to be more related to age, medication and comorbidities than HCM phenotype itself. Lower VO2max is consistently seen in HCM patients at major cardiovascular risk.
Open Access
Cathepsin K expression in melanoma is associated with metastases
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Petricevic, Slavica Juric; Pavlovic, Antonia; Capkun, Vesna; Becic, Kristijan; Durdov, Merica Glavina
Introduction. Melanoma of the skin shows a tendency to metastasize via lymph or blood secreting matrix metalloproteinases and cathepsins, which enable penetration through the dermis. Cathepsin K acts in cytoplasm of atypical melanocytes and completely cleaves internalized collagen. Materials and methods. Expression of cathepsin K was analyzed immunohistochemically in 45 melanomas and correlated to morphological and clinical parameters. Results. During six years follow up, 13 patients developed lymph node metastases and three of them distant metastases. Positive expression of cathepsin K was found in 19 cases. In univariate regression analysis histological type, pagetoid spread, mitotic activity and cathepsin K expression were significantly connected to metastases. Cathepsin K was significantly associated to histologic type, ulceration, pagetoid spread and mitotic rate. In multiple logistic regression adjusted to these variables, cathepsin K was an independent predictor in occurrence of metastases (P=0.015). Median to the occurrence of metastases was 40 months in patients with cathepsin K positive expression and 71 months in patients with cathepsin K negative expression (P<0.001). Conclusions. In this preliminary study positive expression of cathepsin K in melanoma of the skin is associated with other unfavorable prognostic factors. We consider cathepsin K expression in primary tumor would significantly precipitate occurrence of metastases.
Open Access
CD34+ stem cells in chronic myeloproliferative disorders
(Murcia : F. Hernández, 2002) Thiele, J.; Kvasnicka, H.M.
Contrasting the wealth of information that is available about various biological and therapeutic aspects of human CD34+ stem cells, little data ex i s t concerning their quantity and dynamics as well as their mutual relationships with other hematopoietic constituents in the bone marrow of patients with chronic m y e l o p r o l i f e r a t ive disorders. In comparison with a control group frequency of progenitors is signifi c a n t l y increased in chronic myeloid leukemia (CML). Following different therapeutic modalities their quantity reflects therapeutic eff i c a cy (responder and nonresponder patients) and therefore exerts a predictive value regarding acceleration and blastic crisis. The s i g n i ficant correlations between fiber content and number of these precursors elucidates the complex interactions between stroma and progenitor cell d i fferentiation and maturation. Fo l l owing allogeneic bone marrow transplantation there is a rapid recovery of the CD34+ stem cell population in the first month. A higher number of these cells is related with graft size, an earlier independence for platelet transfusion and a more extended regeneration of erythro- and megakaryopoiesis. The slight increase in reticulin fibers in these patients may be associated with the complex and so far illd e fined pathomechanism of homing (adherence to the fibrous matrix). In idiopathic myelofibrosis (IMF) an increased number of CD34 + stem cells is found predominantly in the early (prefibrotic or mild fibrotic) hypercellular stages and probably indicates a higher p r o l i f e r a t ive activity of the precursor cell pool. According to sequential biopsies most patients with early IMF that later evolved into an overt fibrosclerotic stage usually display a reduction of progenitor cells during the development of myelofibrosis. The unequal d i s t r i bution of CD34+ stem cells in the bone marrow versus spleen in IMF (advanced fibrosclerotic stage) is in support of the currently discussed hypothesis of splenic filtration and concentration of precursor cells as an essential feature of myeloid metaplasia. Rega r d i n g prognosis in CML a higher amount of CD34+ stem cells is significantly associated with an unfavorable survival and thus confirms the assumed implication of an accelerated phase of disease at onset. On the other hand, in polycythemia vera (PV) and IMF a low number of progenitors is probably due to a decreased proliferation rate (reduced hematopoietic turnover index) and therefore reflects a reduction in the regenerative capacity of hematopoiesis. For this reason, a presumptive defect in the recovery of normal and clonally transformed stem cells is speculated to add to the worsening of prognosis by causing the well-known bone marrow insufficiency in terminal stage PV and IMF.
Open Access
Clinical significance of FAK expression in human neoplasia
(Murcia : F. Hernández, 2008) Chatzizacharias, Nikolaos A.; Kouraklis, Gregory P.; Theocharis, Stamatios E.
Focal Adhesion Kinase is a 119-121 kDa nonreceptor protein kinase widely expressed in various tissues and cell types. Several studies showed that FAK plays an important role in integrin signaling. Once activated by integrin and non-integrin stimuli, it binds and activates several other molecules, such as Src, p130Cas, Grb2, PI3K and paxillin, thus promoting signaling transduction. In normal cells FAK activity is under constant regulation by mechanisms such as gene amplification, alternative splicing and action of phosphatases. On the contrary, in vitro studies showed that in transformed cells unopposed FAK signaling promoted cancer cells’ malignant characteristics. FAK was held responsible for cancer cells’ uninhibited proliferation, protection from apoptosis, invasion, migration, adhesion and spreading, as well as tumor angiogenesis. Several in vivo studies supported the above observations and further correlated FAK expression with various clinicopathological parameters of several types of human malignancies. The purpose of this article is a comprehensive review of the existing data on FAK expression and signaling and their clinical significance in human malignancy.
Open Access
Clinical significance of SPRY4-IT1 in efficacy and survival prediction in breast cancer patients undergoing neoadjuvant chemotherapy
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Zheng, Ang; Zhang, Lin; Song, Xinyue; Jin, Feng
Breast cancer is the most frequent malignancy and the leading cause of cancer death among females. Long noncoding RNAs (lncRNAs) are under investigation as novel prognostic biomarkers in cancer. The aim of the study was to investigate the expression, clinical implications and prognostic significance of lncRNA SPRY4-IT1, and to identify the predictive value of SPRY4-IT1 on the outcome of chemotherapy in breast cancer patients undergoing neoadjuvant chemotherapy (NACT). Bioinformatics indicated SPRY4-IT1 was related to chemo-resistance in breast cancer. SPRY4-IT1 expression was assessed by qRT-PCR in breast cancer tissues and matched normal breast tissues (n=26 pairs). SPRY4-IT1 expression was also detected by in situ hybridization (ISH) in 60 paraffin slices with complete clinical datum. In this study, SPRY4-IT1 was significantly more expressed in cancer tissues than in normal tissues (P<0.05). Increased SPRY4-IT1 expression was significantly correlated with increased rates of lymph node metastasis (P=0.002) and recurrence (P=0.017). Both were independent factors of SPRY4-IT1 expression (P<0.05). High-SPRY4-IT1 patients had significantly lower overall survival and disease-free survival. High SPRY4-IT1 expression indicated poor clinical response in the whole group, luminal A subgroup and luminal B subgroup (P<0.05) and pathological complete response in the whole group. Overexpression of SPRY4-IT1 promoted chemo- resistance of MCF-7 and MDA-MB-231 cells to epirubicin. SPRY4-IT1 has the potential to be a biomarker to predict NACT efficacy and prognosis in breast cancer patients
Open Access
Clinical significance of stem cell marker CD133 expression in colorectal cancer
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Wang, Bin-Bin; Li, Zhi-juan; Zhang, Feng-Feng; Hou, Hai-Tao; Yu, Jing-Kui; Li, Feng
Objective: CD133, a glycoprotein, is expressed in different types of human stem cells and tumor cells. Detection of altered CD133 expression in colorectal cancer tissues could be useful as a marker for the prediction of colorectal tumorigenesis, progression, and prognosis. Methods: A total of 19 fresh and 145 paraffin-embedded tissue specimens from colorectal cancer patients were obtained for detection of CD133 expression using flow cytometry and immunohistochemistry, respectively. The tumorigenic capacity of tumor cells from 19 patients was assessed in nude mice. Association of CD133 expression was then analyzed for clinical significance. Results: The percentage of CD133- positive (CD133+) tumor cell population ranged between 0.84% and16.75% (mean ratio=7.15%) of tumor cells in the 19 freshly isolated tissue samples. CD133 expression in tumor cells was associated with tumor lymph node metastasis (9.81% vs. 3.22%; p=0.013) and poor tumor differentiation (8.32% vs. 5.07%; p=0.043). In the 145 paraffin-embedded samples, CD133+ colorectal cancer was also associated with local recurrence of tumorigenesis (p=0.035) and distant metastasis (p=0.017), while patients with over 5% CD133+ tumor cells exhibited a decreased survival rate (p=0.001). Multivariate COX analysis showed that the depth of tumor invasion, histology, stages, lymph node metastasis, and CD133 expression were all independent prognosis factors for colorectal cancer (p=0.032, 0.011, 0.001, 0.002, and 0.030, respectively). Furthermore, as few as 5,000 CD133+ colorectal cancer HCT116 cellswere sufficient to form tumor xenografts, whereas 1x105 CD133- tumor cells failed to develop tumor xenografts in nude mice. Conclusions: CD133 expression is a useful biomarker for prediction of colorectal cancer progression and survival of patients.
Open Access
Clinicopathological analysis of retroperitoneal solitary fibrous tumours: a study of 31 cases
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Yuan, Xiaolu; Liu, Yuan; Wang, Xuming; Chen, Yu; Zhang, Lei
. A solitary fibrous tumour (SFT) is a mesenchymal tumour that exhibits fibroblast differentiation and rarely occurs in the retroperitoneum. The main purpose of this study was to explore the clinical manifestation, histopathological features and biological behaviour of retroperitoneal SFT. From 2011 to 2020, 31 patients were hospitalized and diagnosed with retroperitoneal SFTs. We summarized and analysed the morphological features, immunophenotype, treatment and prognosis. Patients (13 M; 18 F) ranged in age from 25 to 79 years with a mean age of 53.6 years. The main symptoms included an abdominal mass (48.4%) and abdominal discomfort (25.8%). The mean maximum diameter of the tumours was 12.9 cm (range, 4-40 cm). Histopathologically, there were 17 classic cases and 14 hemangiopericytoma-like cases. The tumour cells were positive for STAT6 (96.8%), CD34 (96.8%), CD99 (93.5%) and BCL-2 (90.3%). All patients were treated with complete surgical excision, and 3 of the patients also received chemotherapy. After a median follow up period of 44 months (range, 6 to 107 months), 2 patients died. Patients in the high- or intermediate-risk group were prone to metastasis and/or recurrence. The sites of metastases and/or recurrences involved the liver, bone and pelvis. The Ki-67 labelling index in the high-intermediate risk group (median, 10%) was significantly higher than that in the low-risk group (median, 3%). The retroperitoneal SFT demonstrates an indolent clinical course, and patients from the high- or intermediate-risk group require close follow-up. A Ki-67 labelling index ≥10% may be used as an important reference for prognosis.