Roberta Mazzucchelli

Publications (97)312.15 Total impact

• Article: Immunohistochemical expression of prostate tumour overexpressed 1 (PTOV1) in atypical adenomatous hyperplasia (AAH) of the prostate : Additional evidence linking AAH to adenocarcinoma.

  Roberta Mazzucchelli, Marina Scarpelli, Francesca Barbisan, Alfredo Santinelli, Antonio Lopez-Beltran, Liang Cheng, Rodolfo Montironi
  [show abstract] [hide abstract]
  ABSTRACT: BACKGROUND: Prostate tumour overexpressed 1, PTOV1, was recently identified as a novel gene and protein during a differential display screening for genes overexpressed in prostate cancer (PCa). It has been suggested that overexpression of PTOV1 can contribute to the proliferative status of prostate tumour cells and thus to their biological behaviour. METHODS: PTOV1 and Ki67 were immunohistochemically evaluated in PCa, atypical adenomatous hyperplasia (AAH), high-grade prostatic intraepithelial neoplasia (HGPIN), and normal-looking epithelium (NEp) of the transition zone (TZ) in 40 radical prostatectomies with pT2a Gleason score 6 PCa (20 with AAH and 20 with HGPIN) and in 10 simple prostatectomies (SPs) (5 with AAH and 5 with HGPIN). The aim was to evaluate PTOV1 protein expression as a marker for tumor development and progression from AAH to PCa. RESULTS: The proportions of PTOV1 and Ki67 positive cells increased from NEp through AAH and HGPIN to PCa. In particular, the mean Hscore of PTOV1 expression in AAH was 110.90, i.e., close to three times that of NEp (40.76), similar to that of HGPIN (105.61) and lower than that of PCa (137.03). The mean values in AAH and HGPIN associated with cancer in the RPs were slightly higher than in the SPs. CONCLUSION: Our findings related to PTOV1 expression in AAH, similar to those in HGPIN, provide additional evidence linking AAH to prostatic adenocarcinoma.
  Cellular oncology (Dordrecht). 11/2012;
• Article: Multilocular cystic renal cell neoplasms of low malignant potential.

  Roberta Mazzucchelli, Marina Scarpelli, Rodolfo Montironi, Liang Cheng, Antonio Lopez-Beltran
  Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology 10/2012; 34(5):235-8. · 0.41 Impact Factor
• Article: Clinicopathological significance of lymphovascular invasion in urothelial carcinoma.

  Roberta Mazzucchelli, Liang Cheng, Antonio Lopez-Beltran, Marina Scarpelli, Rodolfo Montironi
  [show abstract] [hide abstract]
  ABSTRACT: Lymphovascular invasion is an important prognostic marker in the assessment of bladder cancer, including both cystectomy and transurethral resection of the bladder specimens, and should routinely be reported upon in the pathological report. Strict criteria must be utilized in establishing a diagnosis of lymphovascular invasion in urothelial carcinoma to distinguish it from peritumoral stromal retraction, a common finding that often mimics a vascular space. The use of immunohistochemistry (CD31, CD34, D2-40) for the diagnosis of intravascular invasion in urothelial carcinoma should be used only in selected histologically equivocal cases for confirmation. Routine use of immunohistochemistry for endothelium as a screening test in all cases cannot be recommended.
  Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology 08/2012; 34(4):173-9. · 0.41 Impact Factor
• Article: Classification and grading of noninvasive and invasive neoplasms of the urothelium.

  Roberta Mazzucchelli, Liang Cheng, Antonio Lopez-Beltran, Marina Scarpelli, Rodolfo Montironi
  [show abstract] [hide abstract]
  ABSTRACT: The classification and grading of the noninvasive, intraepithelial neoplasms of the urothelium are based on the morphological pattern of growth, i.e., papillary and flat (and endophytic), and on their degree of architectural and cytologic abnormalities. Recent advances in the morphological, molecular and quantitative evaluation of these lesions have contributed to the refinement of the current classification and grading schemes. However, some controversies on the precise criteria and terminology, especially when the papillary lesions are concerned, are still present.
  Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology 06/2012; 34(3):111-9. · 0.41 Impact Factor
• Article: Spectrum of prostatic nonepithelial tumors and tumorlike conditions with spindle cell features.

  Roberta Mazzucchelli, Marina Scarpelli, Antonio Lopez-Beltran, Liang Cheng, Rodolfo Montironi
  [show abstract] [hide abstract]
  ABSTRACT: There exists a wide and heterogeneous spectrum of spindle cell lesions that can originate from the prostatic stroma. This includes benign and malignant neoplasms as well as tumorlike conditions. Their diagnosis in small biopsy specimens is often difficult because of the potential for sampling error. The utility of ancillary studies, including immunohistochemistry, is often limited and the main criteria for diagnosis are the morphologic findings by routine hematoxylin and eosin stain.
  Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology 06/2012; 34(3):139-44. · 0.41 Impact Factor
• Article: Extent of cancer of less than 50% in any prostate needle biopsy core: how many millimeters are there?

  Rodolfo Montironi, Marina Scarpelli, Roberta Mazzucchelli, Liang Cheng, Antonio Lopez-Beltran, Francesco Montorsi
  European urology 04/2012; 61(4):751-6. · 7.67 Impact Factor
• Article: The spectrum of morphology in non-neoplastic prostate including cancer mimics.

  Rodolfo Montironi, Marina Scarpelli, Roberta Mazzucchelli, Liang Cheng, Antonio Lopez-Beltran
  [show abstract] [hide abstract]
  ABSTRACT: The spectrum of morphology in non-neoplastic prostate includes lesions of prostatic epithelial origin, the most common being atrophy, including partial atrophy, adenosis (atypical adenomatous hyperplasia), basal cell hyperplasia and crowded benign glands, as well as those of non-prostatic origin, such as seminal vesicle epithelium. These lesions often mimic lower-grade prostatic adenocarcinoma whereas others, such as granulomatous prostatitis, for example, are in the differential diagnosis of adenocarcinoma, Gleason grades 4 or 5. Diagnostic awareness of the salient histomorphological and relevant immunohistochemical features of these prostatic pseudoneoplasms is critical to avoid rendering false positive diagnoses of malignancy.
  Histopathology 01/2012; 60(1):41-58. · 3.08 Impact Factor
• Source

  Available from: Antonio Lopez-Beltran

  Article: Handling of radical prostatectomy specimens: total embedding with large-format histology.

  Rodolfo Montironi, Antonio Lopez Beltran, Roberta Mazzucchelli, Liang Cheng, Marina Scarpelli
  [show abstract] [hide abstract]
  ABSTRACT: A problem when handling radical prostatectomy specimens (RPS) is that cancer is often not visible at gross examination, and the tumor extent is always underestimated by the naked eye. The challenge is increased further by the fact that prostate cancer is a notoriously multifocal and heterogeneous tumor. For the pathologist, the safest method to avoid undersampling of cancer is evidently that the entire prostate is submitted. Even though whole mounts of sections from RPS appear not to be superior to sections from standard blocks in detecting adverse pathological features, their use has the great advantage of displaying the architecture of the prostate and the identification and location of tumour nodules more clearly, with particular reference to the index tumour; further, it is easier to compare the pathological findings with those obtained from digital rectal examination (DRE), transrectal ultrasound (TRUS), and prostate biopsies. We are in favour of complete sampling of the RPS examined with the whole mount technique. There are reasons in favour and a few drawbacks. Its implementation does not require an additional amount of work from the technicians' side. It gives further clinical significance to our work of uropathologists.
  International journal of breast cancer. 01/2012; 2012:932784.
• Article: Prostatic intraepithelial neoplasia: its morphological and molecular diagnosis and clinical significance.

  Rodolfo Montironi, Roberta Mazzucchelli, Antonio Lopez-Beltran, Marina Scarpelli, Liang Cheng
  [show abstract] [hide abstract]
  ABSTRACT: The aim of the present paper was to review the morphological spectrum of prostatic intraepithelial neoplasia (PIN), its relationship to carcinoma of the prostate (PCa) and its clinical significance. We reviewed the literature on premalignant lesions of the prostate, with an emphasis on high grade prostatic intraepithelial neoplasia (HGPIN). HGPIN is the most likely precursor of PCa, according to almost all available evidence. HGPIN is characterized by cellular proliferations within pre-existing ducts and acini, with nuclear and nucleolar enlargement similar to PCa. The clinical importance of recognizing HGPIN is based on its association with PCa. In recent years, a significant decline from 36% to 22% in the predictive value of cancer after an initial diagnosis of HGPIN. A major factor contributing to the decreased incidence of cancer after a diagnosis of HGPIN on needle biopsy in the contemporary era is related to increased needle biopsy core sampling, which detects many associated cancers on initial biopsy. Some recent studies have suggested that molecular findings associated with HGPIN might be able to predict which men are more likely to have cancer on re-biopsy.
  BJU International 08/2011; 108(9):1394-401. · 2.84 Impact Factor
• Article: Handling of radical prostatectomy specimens: total embedding with whole mounts, with special reference to the Ancona experience.

  Rodolfo Montironi, Antonio Lopez-Beltran, Marina Scarpelli, Roberta Mazzucchelli, Liang Cheng
  Histopathology 08/2011; 59(5):1006-10; author reply 1010-1. · 3.08 Impact Factor
• Article: A randomized phase IIb presurgical study of finasteride vs. low-dose flutamide vs. placebo in men with prostate cancer. Efficacy monitored by karyometry☆

  Rodolfo Montironi, Peter H Bartels, Andrea Decensi, Matteo Puntoni, Rodolfo Hurle, Ottavio Decobelli, Giorgio Carmignani, Roberta Mazzucchelli, Hubert G Bartels, David S Alberts, Massimo Maffezzini
  [show abstract] [hide abstract]
  ABSTRACT: OBJECTIVE: Presurgical, window of opportunity trials have been proposed as a model to assess the activity of preventive and therapeutic interventions in a cost-effective manner in prostate cancer (CaP). The aim of the study was to explore karyometry as a method for monitoring the efficacy of intervention with preventive agents in patients with CaP. MATERIALS AND METHODS: The material used in this investigation was from the 2F study, i.e., an Italian prospective randomized phase IIb presurgical study of finasteride vs. low-dose flutamide vs. placebo in men with CaP. Image analysis was performed in 16 cases treated with finasteride, 24 with flutamide, and 20 with placebo. For all these cases, CaP and normal looking secretory epithelium were present in the pretreatment biopsies as well as the post-treatment ex-vivo biopsies obtained from the radical prostatectomy specimens. RESULTS: To establish a direction of nuclear change from normal to malignancy, i.e., the so-called line of progression, a discriminant function was derived with the normal looking epithelium in the pretreatment biopsies as one endpoint, and the CaP in the pretreatment biopsies as the other. The discriminant function was then applied to the post-treatment groups. The increase in relative nuclear area was the dominant feature. In the placebo group, 15 out of 20 CaP (75%) cases had a higher discriminant function score at the end of study, with a significant increase of the mean score by 90%. The flutamide treated CaP cases had increased discriminant function scores in 19 out of 24 cases (79%) and an increase of the mean score by 43%; the 5 cases with lower scores involved only minor reductions. In contrast, the finasteride treated CaP cases had increased discriminant function scores for 8 out of 16 cases (50%), but the increase in the mean score was by only 8%. CONCLUSION: This exploratory study establishes that karyometric monitoring can track the results of subtle nuclear changes induced by preventive interventions in men with CaP, thus allowing assessment of agent activity in a cost-effective manner.
  Urologic Oncology 07/2011; · 3.22 Impact Factor
• Article: Immunohistochemical expression of prostate tumor overexpressed 1 in cystoprostatectomies with incidental and insignificant prostate cancer. Further evidence for field effect in prostatic carcinogenesis.

  Roberta Mazzucchelli, Francesca Barbisan, Alfredo Santinelli, Antonio Lopez-Beltran, Liang Cheng, Marina Scarpelli, Rodolfo Montironi
  [show abstract] [hide abstract]
  ABSTRACT: Prostate tumor overexpressed 1 was recently identified as a novel gene and protein during a differential display screening for genes overexpressed in prostate cancer. It has been suggested that overexpression of prostate tumor overexpressed 1 can contribute to the proliferative status of prostate tumor cells and, thus, to their biologic behavior. Prostate tumor overexpressed 1 and Ki-67 were immunohistochemically evaluated in prostate cancer, high-grade prostatic intraepithelial neoplasia, and normal-looking epithelium in 20 cystoprostatectomies and 20 radical prostatectomies with pT2a Gleason score 6 prostate cancer. The aim was to see whether there were differences in marker expression between cystoprostatectomies and radical prostatectomies. The proportions of prostate tumor overexpressed 1- and Ki-67-positive cells in the cystoprostatectomies and radical prostatectomies increased from normal-looking epithelium through high-grade prostatic intraepithelial neoplasia, away from and adjacent to prostate cancer, to prostate cancer. Prostate tumor overexpressed 1 expression in prostate cancer in cystoprostatectomies was lower than in radical prostatectomies, the differences being significant; there were significant differences in Ki-67 indices. In conclusion, our findings related to prostate tumor overexpressed 1 expression in high-grade prostatic intraepithelial neoplasia, evaluated adjacent and away from prostate cancer, and in incidental and clinical cancers give further support to the concept of field effect in prostatic carcinogenesis as well as to differences in the process of prostatic carcinogenesis between cystoprostatectomies and radical prostatectomies.
  Human pathology 06/2011; 42(12):1931-6. · 3.03 Impact Factor
• Article: Comparison of incidentally detected prostate cancer with screen-detected prostate cancer treated by prostatectomy.

  Tineke Wolters, Rodolfo Montironi, Roberta Mazzucchelli, Marina Scarpelli, Monique J Roobol, Roderick C N van den Bergh, Pim J van Leeuwen, Robert F Hoedemaeker, Geert J L H van Leenders, Fritz H Schröder, Theodorus H van der Kwast
  [show abstract] [hide abstract]
  ABSTRACT: The prostate may often harbor a prostate cancer (PC) which will not cause morbidity if left untreated. Screening for PC leads to increased detection of these insignificant cancers. Objective of this study is to compare PC detected by PSA screening at subsequent screening rounds and treated by radical prostatectomy (RP) with PC incidentally found in cystoprostatectomy specimens. Radical prostatectomy specimens of 617 screen-detected PC were compared with 123 PC identified in cystoprostatectomy specimens. Surgical specimens were systematically examined and stage, grade, tumor volume were recorded. Next, we classified PC as clinically significant or insignificant (i.e., tumor volume <0.5 cm(3), absence of Gleason pattern 4/5, organ confined). Pathological features of incidentally detected PC were compared with PC detected in subsequent screening rounds and with screen-detected T1c PC. Screen-detected PC overall were more often multifocal, larger in volume, more advanced in tumor stage and of higher grade, while the frequency of insignificant PC was lower as compared to those in cystoprostatectomy specimens. This effect became more pronounced during subsequent screening rounds. Screen-detected T1c PC were also more often multifocal (73% vs. 37%) in average fivefold larger (0.85 cm(3) vs. 0.16 cm(3)), less often organ confined (81% vs. 94%), and less frequently clinically insignificant (33% vs. 81%). Screen-detected (T1c) PC treated with RP shows more aggressive features than incidentally found PC. This PSA screening-related selection seems to be mainly driven by tumor volume and-in later screening rounds-by the preferential treatment by prostatectomy of more aggressive PC.
  The Prostate 05/2011; 72(1):108-15. · 3.48 Impact Factor
• Article: Immunohistochemical expression and localization of somatostatin receptor subtypes in androgen ablated prostate cancer.

  Roberta Mazzucchelli, Doriana Morichetti, Alfredo Santinelli, Marina Scarpelli, Aldo V Bono, Antonio Lopez-Beltran, Liang Cheng, Rodolfo Montironi
  [show abstract] [hide abstract]
  ABSTRACT: The aim was to examine the expression and localization of the five somatostatin receptors (termed SSTR1 to 5) in radical prostatectomies (RPs) from patients with prostatic adenocarcinoma (PCa) under complete androgen ablation (CAA) before operation. The five SSTRs were evaluated in the epithelial, smooth muscle and endothelial cells of normal-looking epithelium (Nep), high-grade prostatic intraepithelial neoplasia (HGPIN) and PCa in 20 RPs with clinically detected PCa from patients under CAA. Twenty RPs with clinically detected PCa from hormonally untreated patients were used as control group. Concerning the secretory cells (i) Membrane staining was seen for SSTR3 and SSTR4; the mean percentages of positive cells, higher in SSTR3 than in SSTR4, decreased sharply in HGPIN and PCa compared with Nep; the mean percentages in the androgen ablated group were 30% to 90% lower than in the untreated; (ii) Cytoplasmic staining was seen for all five SSTRs; the mean percentages of positive cells in Nep, HGPIN and PCa of the untreated group were similar, and in general as high as 80% or more; in the treated group, the Nep values were similar to those in the untreated, whereas the values in HGPIN and PCa were lower for SSTR1, three and five, with a decrease of 30% for SSTR1; (iii) Nuclear staining was seen with SSTR4 and SSTR5, the mean percentages for the former being much lower than for the latter; treatment affected both HGPIN and PCa, whose proportions of stained cells were 30% to 55% lower than in the untreated group. Cytoplasmic staining in the basal cells was seen for all five SSTRs, both in Nep and HGPIN. The values in the treated group were lower than in the other, the difference between the two group being in general comprised between 10% and 40%. Treatment did not affect SSTR staining in the smooth muscle and endothelial cells. The present study expands our knowledge on the expression and localization of the five SSTRs in the prostate following CAA.
  Cellular oncology (Dordrecht). 04/2011; 34(3):235-43.
• Article: Editorial comment to When should we expect no residual tumor (pT0) once we submit incidental T1a-b prostate cancers to radical prostatectomy?

  Rodolfo Montironi, Liang Cheng, Antonio Lopez-Beltran, Roberta Mazzucchelli, Marina Scarpelli
  International Journal of Urology 02/2011; 18(2):153-4. · 1.75 Impact Factor
• Source

  Available from: Antonio Lopez-Beltran

  Article: How much do you know about benign, preneoplastic, non-invasive and invasive neoplastic lesions of the urinary bladder classified according to the 2004 WHO scheme?

  Rodolfo Montironi, Liang Cheng, Marina Scarpelli, Roberta Mazzucchelli, Antonio Lopez-Beltran
  [show abstract] [hide abstract]
  ABSTRACT: The aim of this essay is the self assessment of the level of knowledge of the 2004 WHO classification of bladder neoplasms through a series of MCQs, each associated a short commentary. This paper is directed to all who are involved with the application of this classification at the anticancer research, diagnostic, prognostic and therapeutic levels, in particular to uropathologists, urologists and oncologists.
  Diagnostic Pathology 01/2011; 6:31. · 1.64 Impact Factor
• Source

  Available from: Andrea B Galosi

  Article: Specimen orientation by marking the peripheral end: (potential) clinical advantages in prostate biopsy.

  Andrea Benedetto Galosi, Giovanni Muzzonigro, Vito Lacetera, Roberta Mazzucchelli
  [show abstract] [hide abstract]
  ABSTRACT: The aim of this paper is to identify advantages that could be obtained by orientation of the biopsy specimen using the marking technique. We reviewed our experience (4,500 cases) and the published literature. The peripheral (proximal) end of the fresh specimen is marked with ink soon after needle delivering in a few minutes. It is performed easily in association with pre-embedding method. Five potential clinical advantages were identified: (1) tumor localization, (2) atypical lesions localization and planning rebiopsy strategy, (3) planning surgical strategy, (4) selection criteria for focal therapy and active surveillance, and (5) cost reduction. Peripheral end marking is low cost, easy and reproducible. It drives several potential advantages in cancer diagnosis or isolated atypical lesions, in particular, spatial localization within the biopsy (transition versus peripheral zone, anterior versus posterior, subcapsular versus intraparenchima, and extraprostatic extension) should be easy and reliable. We can add a new pathological parameter: pathological orientation or biopsy polarity.
  Prostate cancer. 01/2011; 2011:270403.
• Article: Reply to Kiril Trpkov, Asli Yilmaz' Letter to the Editor re: Rodolfo Montironi, Liang Cheng, Antonio Lopez-Beltran, et al. Original Gleason System Versus 2005 ISUP Modified Gleason System: The Importance of Indicating Which System Is Used in the Patient's Pathology and Clinical Reports. Eur Urol 2010;58:369-73.

  Rodolfo Montironi, Liang Cheng, Antonio Lopez-Beltran, Marina Scarpelli, Roberta Mazzucchelli, Gregor Mikuz, Ziya Kirkali, Francesco Montorsi
  European urology 12/2010; · 7.67 Impact Factor
• Article: Somatostatin receptor subtypes in hormone-refractory (castration-resistant) prostatic carcinoma.

  Roberta Mazzucchelli, Doriana Morichetti, Marina Scarpelli, Aldo V Bono, Antonio Lopez-Beltran, Liang Cheng, Ziya Kirkali, Rodolfo Montironi
  [show abstract] [hide abstract]
  ABSTRACT: The aim of this study was to examine the tissue expression and localisation of the somatostatin receptors (SSTRs) in hormone-refractory (HR) prostate cancer (PCa). Five SSTRs were evaluated immunohistochemically in 20 radical prostatectomies (RPs) with Gleason score (GS) 3+3=6 PCa, in 20 RPs with GS 4+4=8 and 4+5=9 PCa, and 20 transurethral resection of the prostate specimens with HR PCa. The mean values in the cytoplasm (all five SSTRs were expressed), membrane (only SSTR3 and SSTR4 were expressed) and nuclei (only SSTR4 and SSTR5 were expressed) of the glands in HR PCa were 20-70% lower than in the other two groups, the differences being statistically significant. All five SSTRs were expressed in the smooth muscle and endothelial cells of HR PCa, the mean values being lower than in the other two groups. In conclusion, this study expands our knowledge on the expression and localisation of five SSTRs in the various tissue components in the HR PCa compared with hormone-sensitive PCa.
  Asian Journal of Andrology 12/2010; 13(2):242-7. · 1.52 Impact Factor
• Source

  Available from: Antonio Lopez-Beltran

  Article: Inverted (endophytic) noninvasive lesions and neoplasms of the urothelium: the Cinderella group has yet to be fully exploited.

  Rodolfo Montironi, Liang Cheng, Antonio Lopez-Beltran, Marina Scarpelli, Roberta Mazzucchelli, Gregor Mikuz, Ziya Kirkali, Francesco Montorsi
  European urology 11/2010; 59(2):225-30. · 7.67 Impact Factor