Browsing by Author "Nottegar, Alessia"

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    Alternative lengthening of telomeres (ALT) influences survival in soft tissue sarcomas: a systematic review with meta-analysis
    (BMC, 2019-03-14) Lawlor, Rita T.; Veronese, Nicola; Pea, Antonio; Nottegar, Alessia; Smith, Lee; Pilati, Camilla; Demurtas, Jacopo; Fassan, Matteo; Cheng, Liang; Luchini, Claudio; Pathology and Laboratory Medicine, School of Medicine
    Alternative lengthening of telomeres (ALT) is a telomerase-independent mechanism used by a broad range of neoplasms to maintain telomere length, permitting uncontrolled replication during their progression. ALT has been described in different types of sarcoma, but a comprehensive analysis of its clinical significance is still lacking. Therefore, we provide here the first meta-analysis on this topic. METHODS: We searched SCOPUS and PubMed through July 2018 to identify all studies that investigated the prognostic role of ALT in sarcomas. We considered the risk of death (risk ratio, RR) calculated as the number of death vs. total participants during follow-up in ALT+ versus ALT- patients as the primary outcome. The secondary outcome was the hazard ratio (HR), adjusted for the maximum number of covariates available, using ALT- patients as reference. RESULTS: Eight articles comprising a total of 551 patients with sarcomas (226 ALT+ and 325 ALT-) were selected. The ALT+ group showed a higher mitotic count and a higher tumor grade compared with the ALT- group (p < 0.01). Furthermore, we demonstrate a strong impact of ALT on survival. In fact, ALT+ patients showed a statistically significant higher risk of death than ALT- patients, when also considering data from multivariate analyses (RR = 1.50; 95% CI: 1.15-1.96; p = 0.003; HR = 2.02; 95% CI: 1.22-3.38; p = 0.007). CONCLUSIONS: Our results indicate that ALT is associated with an increased risk of death in patients with sarcoma. In these neoplasms, ALT should be taken into account for a precise prognostic stratification and design of potential therapeutic strategies.
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    Extranodal extension of lymph node metastasis influences recurrence in prostate cancer: a systematic review and meta-analysis
    (SpringerNature, 2017-05-24) Luchini, Claudio; Fleischmann, Achim; Boormans, Joost L.; Fassan, Matteo; Nottegar, Alessia; Lucato, Paola; Stubbs, Brendon; Solmi, Marco; Porcaro, Antonio; Veronese, Nicola; Brunelli, Matteo; Scarpa, Aldo; Cheng, Liang; Department of Pathology and Laboratory Medicine, School of Medicine
    The extranodal extension (ENE) of nodal metastasis involves the extension of neoplastic cells through the lymph node capsule into the perinodal adipose tissue. This morphological feature has recently been indicated as an important prognostic factor in various cancer types, but its role in prostate cancer is still unclear. We aimed to clarify it, performing the first meta-analysis on this issue, comparing prognostic parameters in surgically treated, node-positive prostate cancer patients with (ENE+) vs. without (ENE-) ENE. Data were summarized using risk ratios (RRs) for number of deaths/recurrences and hazard ratios (HRs), with 95% confidence intervals (CI), for the time-dependent risk related to ENE positivity. Six studies followed-up 1,113 patients with N1 prostate cancer (658 ENE+ vs. 455 ENE-) for a median of 83 months. The presence of ENE was associated with a significantly higher risk of biochemical recurrence (RR = 1.15; 95%CI: 1.03-1.28; I2 = 0%; HR = 1.40, 95%CI: 1.12-1.74; I2 = 0%) and "global" (biochemical recurrence and distant metastasis) recurrence (RR = 1.15; 95%CI: 1.04-1.28; I2 = 0%; HR = 1.41, 95%CI: 1.14-1.74; I2 = 0%). ENE emerged as a potential prognostic moderator, earmarking a subgroup of patients at higher risk of recurrence. It may be considered for the prognostic stratification of metastatic patients. New possible therapeutic approaches may explore more in depth this prognostic parameter.
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    Liquid Biopsy as Surrogate for Tissue for Molecular Profiling in Pancreatic Cancer: A Meta-Analysis Towards Precision Medicine
    (MDPI, 2019-08-10) Luchini, Claudio; Veronese, Nicola; Nottegar, Alessia; Cappelletti, Vera; Daidone, Maria G.; Smith, Lee; Parris, Christopher; Brosens, Lodewijk A. A.; Caruso, Maria G.; Cheng, Liang; Wolfgang, Christopher L.; Wood, Laura D.; Milella, Michele; Salvia, Roberto; Scarpa, Aldo; Pathology and Laboratory Medicine, School of Medicine
    Liquid biopsy (LB) is a non-invasive approach representing a promising tool for new precision medicine strategies for cancer treatment. However, a comprehensive analysis of its reliability for pancreatic cancer (PC) is lacking. To this aim, we performed the first meta-analysis on this topic. We calculated the pooled sensitivity, specificity, positive (LR+) and negative (LR-) likelihood ratio, and diagnostic odds ratio (DOR). A summary receiver operating characteristic curve (SROC) and area under curve (AUC) were used to evaluate the overall accuracy. We finally assessed the concordance rate of all mutations detected by multi-genes panels. Fourteen eligible studies involving 369 patients were included. The overall pooled sensitivity and specificity were 0.70 and 0.86, respectively. The LR+ was 3.85, the LR- was 0.34 and DOR was 15.84. The SROC curve with an AUC of 0.88 indicated a relatively high accuracy of LB for molecular characterization of PC. The concordance rate of all mutations detected by multi-genes panels was 31.9%. LB can serve as surrogate for tissue in the molecular profiling of PC, because of its relatively high sensitivity, specificity and accuracy. It represents a unique opportunity to be further explored towards its introduction in clinical practice and for developing new precision medicine approaches against PC.
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    PD-1, PD-L1 and CD163 in pancreatic undifferentiated carcinoma with osteoclast-like giant cells: expression patterns and clinical implications
    (Elsevier, 2018) Luchini, Claudio; Cros, Jerome; Pea, Antonio; Pilati, Camilla; Veronese, Nicola; Rusev, Borislav; Capelli, Paola; Mafficini, Andrea; Nottegar, Alessia; Brosens, Lodewijk A. A.; Noë, Michaël; Offerhaus, G. Johan A.; Chianchiano, Peter; Riva, Giulio; Piccoli, Paola; Parolini, Claudia; Malleo, Giuseppe; Lawlor, Rita T.; Vincenzo, Corbo; Sperandio, Nicola; Barbareschi, Mattia; Fassan, Matteo; Cheng, Liang; Wood, Laura D.; Scarpa, Aldo; Pathology and Laboratory Medicine, School of Medicine
    Undifferentiated carcinoma with osteoclast-like giant cells (UCOGC), a variant of pancreatic ductal adenocarcinoma (PDAC), has striking genetic similarity to PDAC but a significantly improved overall survival. We hypothesize that this difference could be due to the immune response to the tumor, and as such, we investigated the expression of PD-1, PD-L1 and CD163 in a series of UCOGC. To this aim, 27 pancreatic UCOGCs (11 pure and 16 PDAC-associated), 5 extra-pancreatic tumors with osteoclast-like giant cells and 10 pancreatic anaplastic carcinomas (ACs) were immunostained using antibodies against PD-1, PD-L1 and CD163. In pancreatic UCOGCs, PD-L1 was expressed in neoplastic cells of 17/27 (63%) cases, more often in cases with an associated PDAC (P = .04). Expression of PD-L1 was associated with poor prognosis, confirmed by multivariate analysis: patients with PD-L1-positive UCOGCs had a risk of all-cause mortality that was 3 times higher than patients with PD-L1-negative UCOGCs (HR: 3.397, 95%CI: 1.023–18.375, P = .034). PD-L1 expression on tumor cells was also associated with aberrant P53 expression (P = .035). PD-1 was expressed on rare lymphocytes in 12 UCOGCs (44.4%), mainly located at the tumor periphery. CD163 was expressed on histiocytes, with a diffuse and strong staining pattern in all UCOGCs. Extra-pancreatic tumors with osteoclast-like giant cells showed very similar staining patterns for the same proteins. ACs have some similarities to UCOGCs, but PD-L1 has no prognostic roles. Our results may have important implications for immunotherapeutic strategies in UCOGCs; these tumors may also represent a model for future therapeutic approaches against PDAC.
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    Prognostic Role of High-Grade Tumor Budding in Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-Analysis with a Focus on Epithelial to Mesenchymal Transition
    (MDPI, 2019-01-19) Lawlor, Rita T.; Veronese, Nicola; Nottegar, Alessia; Malleo, Giuseppe; Smith, Lee; Demurtas, Jacopo; Cheng, Liang; Wood, Laura D.; Silvestris, Nicola; Salvia, Roberto; Scarpa, Aldo; Luchini, Claudio; Pathology and Laboratory Medicine, School of Medicine
    This study aims at clarifying the prognostic role of high-grade tumor budding (TB) in pancreatic ductal adenocarcinoma (PDAC) with the first systematic review and meta-analysis on this topic. Furthermore, we analyzed with a systematic review the relationship between TB and a recently suggested TB-associated mechanism: the epithelial to mesenchymal transition (EMT). Analyzing a total of 613 patients, 251 of them (40.9%) with high grade-TB, we found an increased risk of all-cause mortality (RR, 1.46; 95% CI, 1.13⁻1.88, p = 0.004; HR, 2.65; 95% CI, 1.79⁻3.91; p < 0.0001) and of recurrence (RR, 1.61; 95% CI, 1.05⁻2.47, p = 0.03) for PDAC patients with high-grade TB. Moreover, we found that EMT is a central process in determining the presence of TB in PDAC. Thanks to this meta-analysis, we demonstrate the potential clinical significance of high-grade TB for prognostic stratification of PDAC. TB also shows a clear association with the process of EMT. Based on the results of the present study, TB should be conveyed in pathology reports and taken into account by future oncologic staging systems.