Browsing by Author "Mazzucchelli, Roberta"
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Item Androgen Receptor Signaling Pathway in Prostate Cancer: From Genetics to Clinical Applications(MDPI, 2020-12) Aurilio, Gaetano; Cimadamore, Alessia; Mazzucchelli, Roberta; Lopez-Beltran, Antonio; Verri, Elena; Scarpelli, Marina; Massari, Francesco; Cheng, Liang; Santoni, Matteo; Montironi, Rodolfo; Pathology and Laboratory Medicine, School of MedicineAround 80–90% of prostate cancer (PCa) cases are dependent on androgens at initial diagnosis; hence, androgen ablation therapy directed toward a reduction in serum androgens and the inhibition of androgen receptor (AR) is generally the first therapy adopted. However, the patient’s response to androgen ablation therapy is variable, and 20–30% of PCa cases become castration resistant (CRPCa). Several mechanisms can guide treatment resistance to anti-AR molecules. In this regard, AR-dependent and -independent resistance mechanisms can be distinguished within the AR pathway. In this article, we investigate the multitude of AR signaling aspects, encompassing the biological structure of AR, current AR-targeted therapies, mechanisms driving resistance to AR, and AR crosstalk with other pathways, in an attempt to provide a comprehensive review for the PCa research community. We also summarize the new anti-AR drugs approved in non-metastatic castration-resistant PCa, in the castration-sensitive setting, and combination therapies with other drugs.Item Contemporary grading of prostate cancer: 2017 update for pathologists and clinicians(Wolters Kluwer, 2017-08-04) Gasparrini, Silvia; Cimadamore, Alessia; Scarpelli, Marina; Massari, Francesco; Doria, Andrea; Mazzucchelli, Roberta; Cheng, Liang; Lopez-Beltran, Antonio; Montironi, Rodolfo; Pathology and Laboratory Medicine, School of MedicineThe Gleason grading system for prostate cancer (PCa) was developed in the 1960s by DF Gleason. Due to changes in PCa detection and treatment, the application of the Gleason grading system has changed considerably in pathology routine practice. Two consensus conferences were held in 2005 and in 2014 to update PCa Gleason grading. This review provides a summary of the changes in the grading of PCa from the original Gleason grading system to the prognostic grade grouping, as well as a discussion of the clinical significance of the percentage of Gleason patterns 4 and 5.Item Does prostate acinar adenocarcinoma with Gleason Score 3 + 3 = 6 have the potential to metastasize?(BioMed Central, 2014-10-18) Montironi, Rodolfo; Scarpelli, Marina; Mazzucchelli, Roberta; Lopez-Beltran, Antonio; Santoni, Matteo; Briganti, Alberto; Montorsi, Francesco; Cheng, Liang; Department of Pathology & Laboratory Medicine, School of MedicineBackground: There is a worldwide debate involving clinicians, uropathologists as well as patients and their families on whether Gleason score 6 adenocarcinoma should be labelled as cancer. Case description: We report a case of man diagnosed with biopsy Gleason score 6 acinar adenocarcinoma and classified as low risk (based on a PSA of 5 ng/mL and stage cT2a) whose radical prostatectomy specimen initially showed organ confined Gleason score 3 + 3 = 6, WHO nuclear grade 3, acinar adenocarcinoma with lymphovascular invasion and secondary deposit in a periprostatic lymph node. When deeper sections were cut to the point that almost all the slice present in the paraffin block was sectioned, a small tumor area (<5% of the whole tumor) of Gleason pattern 4 (poorly formed glands) was found in an extraprostatic position. Conclusion: The epilogue was that the additional finding changed the final Gleason score to 3 + 3 = 6 with tertiary pattern 4 and the stage to pT3a. Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/ vs/13000_2014_190Item Immunohistochemical detection and localization of somatostatin receptor subtypes in prostate tissue from patients with bladder outlet obstruction(IOS Press, 2008) Montironi, Rodolfo; Cheng, Liang; Mazzucchelli, Roberta; Morichetti, Doriana; Stramazzotti, Daniela; Santinelli, Alfredo; Moroncini, Gianluca; Galosi, Andrea B.; Muzzonigro, Giovanni; Comeri, Giancarlo; Lovisolo, Jon; Cosciani-Cunico, Sergio; Bono, Aldo V.; Pathology and Laboratory Medicine, School of MedicineBackground and aim of the study: Scant information on the cellular distribution of the five somatostatin receptor (SSTR) subtypes in the normal prostate and in neoplasms of the prostate has been reported in very few studies in which techniques, such as in situ hybridization histochemistry, autoradiography, and more recently immunohistochemistry, have been applied. The aim of the study was to examine immunohistochemically the distribution and localization of these 5 subtypes in the various tissue components in normal prostate. Materials: The study was conducted in 14 surgical specimens of normal prostate tissue from adenomectomy specimens from patients with bladder outlet obstruction. The distribution and localization of the 5 somatostatin receptor (SSTR) subtypes was investigated with an immunohistochemical technique. Specificity of the antibodies against the 5 receptor subtypes was preliminarily investigated. Results: Close to 90% of secretory cells showed a weak positivity in the cytoplasm, the proportion ranging from 86.3% (SSTR4) to 89.9% (SSTR5). Strong immunoreactivity was seen in a small proportion of cells, ranging from 0.8% (SSTR3) to 3.2% (SSTR1). For the subtypes 1 and 3 the greatest proportion of basal cells showed a moderate intensity (42.5 and 41.4%, respectively), strong immunoreactivity being observed only in 18.1 and 15.8% of cells, respectively. For the subtypes 2, 4 and 5, the majority of cells showed a weak intensity (72.3, 65.7 and 65.1%, respectively). Subtype 1 showed a strong immunoreactivity in the cytoplasm in 60% of the smooth muscle cells. With subtypes 2, 3 and 4 the greatest proportion of cells showed a weak intensity (63.4, 89.8 and 81.7%, respectively). With the subtype 5 the majority of cells (59.8%) were negative. Subtype 1 showed a strong immunoreactivity in the cytoplasm in 98.6% of the endothelial cells. With subtypes 3 and 4 the greatest proportion of cells showed a weak intensity (73.5 and 56.4%, respectively). With the subtype 2 and 5 the majority of cells were negative (59.1 and 50.7%, respectively).Item Long Non-coding RNAs in Prostate Cancer with Emphasis on Second Chromosome Locus Associated with Prostate-1 Expression(Frontiers Media, 2017-12-12) Cimadamore, Alessia; Gasparrini, Silvia; Mazzucchelli, Roberta; Doria, Andrea; Cheng, Liang; Lopez-Beltran, Antonio; Santoni, Matteo; Scarpelli, Marina; Montironi, Rodolfo; Pathology and Laboratory Medicine, School of MedicineLong non-coding RNAs (lncRNAs) are a class of RNA with transcripts longer than 200 nucleotides that lack functional open reading frames. They play various roles in human carcinoma, such as dysregulating gene expression in prostate cancer (PCa), which results in cancer initiation, development, and progression. The non-coding RNA SChLAP1 (second chromosome locus associated with prostate-1) is highly expressed in approximately 25% of PCas with higher prevalence in metastatic compared to localized PCa. Its expression is detectable non-invasively in PCa patient urine samples. Experimental data suggest that targeting SChLAP1 may represent a novel therapeutic application in PCa. This contribution focuses on the role of lncRNAs SChLAP1 expression in PCa diagnosis and prognosis.Item Narrative review of prostate cancer grading systems: will the Gleason scores be replaced by the Grade Groups?(AME Publishing, 2021-03) Montironi, Rodolfo; Cheng, Liang; Cimadamore, Alessia; Mazzucchelli, Roberta; Scarpelli, Marina; Santoni, Matteo; Massari, Francesco; Lopez-Beltran, Antonio; Pathology and Laboratory Medicine, School of MedicineThe Gleason grading system, proposed by Dr. Donald F. Gleason in 1966, is one of the most important prognostic factors in men with prostate cancer (PCa). At consensus conferences held in 2005 and 2014, organized by the International Society of Urological Pathology (ISUP), the system was modified to reflect the current diagnostic and therapeutic approaches. In particular, in the 2014 Conference, it was recognized that there were weaknesses with the original and the 2005 ISUP modified Gleason systems. Based on the results of a research conducted by Prof. JI Epstein and his group, a new grading system was proposed by the ISUP in order to address some of such deficiencies: i.e., the five distinct Grade Groups (GGs). Since 2014, results of studies have been published by different groups and societies, including the Genitourinary Pathology Society (GUPS), giving additional support to the prognostic role of the architectural Gleason patterns and, in particular, of the GGs. A revised GG system, taking into account the percentage of Gleason pattern (GP) 4, cribriform and intraductal carcinoma, tertiary GP 5, and reactive stroma grade, has shown to have some advantages, however not ready for adoption in the current practice. The aim of this contribution was to review the major updates and recommendations regarding the GPs and GSs, as well as the GGs, trying to give an answer to the following questions: “How has the grade group system been used in the routine?” and “will the Gleason scoring system be replace by the grade groups?” We also discussed the potential implementation in the future of molecular pathology and artificial intelligence in grading to further define risk groups in patients with PCa.Item Predicting future cancer burden in the United States by artificial neural networks(Taylor & Francis, 2021) Piva, Francesco; Tartari, Francesca; Giulietti, Matteo; Aiello, Marco Maria; Cheng, Liang; Lopez-Beltran, Antonio; Mazzucchelli, Roberta; Cimadamore, Alessia; Cerqueti, Roy; Battelli, Nicola; Montironi, Rodolfo; Santoni, Matteo; Pathology and Laboratory Medicine, School of MedicineAims: To capture the complex relationships between risk factors and cancer incidences in the US and predict future cancer burden. Materials & methods: Two artificial neural network (ANN) algorithms were adopted: a multilayer feed-forward network (MLFFNN) and a nonlinear autoregressive network with eXogenous inputs (NARX). Data on the incidence of the four most common tumors (breast, colorectal, lung and prostate) from 1992 to 2016 (available from National Cancer Institute online datasets) were used for training and validation, and data until 2050 were predicted. Results: The rapid decreasing trend of prostate cancer incidence started in 2010 will continue until 2018-2019; it will then slow down and reach a plateau after 2050, with several differences among ethnicities. The incidence of breast cancer will reach a plateau in 2030, whereas colorectal cancer incidence will reach a minimum value of 35 per 100,000 in 2030. As for lung cancer, the incidence will decrease from 50 per 100,000 (2017) to 31 per 100,000 in 2030 and 26 per 100,000 in 2050. Conclusion: This up-to-date prediction of cancer burden in the US could be a crucial resource for planning and evaluation of cancer-control programs.Item Prostate cancer glands with cribriform architecture and with glomeruloid features should be considered as Gleason pattern 4 and not pattern 3(2016-06) Minardi, Daniele; Mazzucchelli, Roberta; Scarpelli, Marina; Massari, Francesco; Ciccarese, Chiara; Lopez-Beltran, Antonio; Cheng, Liang; Montironi, Rodolfo; Department of Pathology and Laboratory Medicine, IU School of MedicineItem Prostate Cancer in 2021: Novelties in Prognostic and Therapeutic Biomarker Evaluation(MDPI, 2021-07-11) Cimadamore, Alessia; Mazzucchelli, Roberta; Lopez-Beltran, Antonio; Massari, Francesco; Santoni, Matteo; Scarpelli, Marina; Cheng, Liang; Montironi, Rodolfo; Pathology and Laboratory Medicine, School of MedicineThe 2021 novelties in prognostic and therapeutic tissue markers in patients with prostate cancer (PCa) can be subdivided into two major groups. The first group is related to prognostic markers based on morphological and immunohistochemical evaluations. The novelties in this group can then be subdivided into two subgroups, one involving morphologic evaluation only, i.e., PCa grading, and the other involving both morphologic and immunohistochemical evaluations, i.e., aggressive variant PCa (AVPCa). Grading concerns androgen-dependent PCa, while AVPCa represents a late phase in its natural history, when it becomes androgen-independent. The novelties of the other major group are related to molecular markers predicting significant disease or response to therapy. This group mainly includes novelties in the molecular evaluation of PCa in tissue material and liquid biopsies.Item Role of the pathologist in active surveillance for prostate cancer(2015-02) Mazzucchelli, Roberta; Galosi, Andrea B.; Santoni, Matteo; Lopez-Beltran, Antonio; Scarpelli, Marina; Cheng, Liang; Montironi, Rodolfo; Department of Pathology and Laboratory Medicine, IU School of MedicineActive surveillance (AS) is an alternative strategy that aims to minimize overtreatment by selecting only patients with significant prostate cancer (PCa) tumors for immediate treatment. Patients with favorable tumor characteristics are closely monitored using serum prostate-specific antigen (PSA) levels and serial biopsies of the prostate. In addition, other predictors of tumor progression, such as PSA doubling time, can be used during AS management. AS represents an excellent opportunity to identify molecular biomarkers of PCa behavior and to develop novel therapeutic strategies.