Biomedical subjects

Roberta Mazzucchelli

Publications and source records attributed to Roberta Mazzucchelli.

30 records · Page 2Linked to original sources

PubMed2004

Immunohistochemical evaluation of urokinase plasminogen activator receptor in noninvasive and early invasive urothelial papillary neoplasia.

OBJECTIVE: To investigate urokinase plasminogen activator receptor (uPAR) expression in urothelial papilloma and in noninvasive and early invasive papillary carcinoma. STUDY DESIGN: The study included 40 cases of papillary neoplasia of the urinary bladder subdivided into 10 cases of urothelial papilloma (UP); 10 of papillary carcinoma, grade 1; 10, grade 2 (G2); and 10, grade 3 (G3). Invasion of the subepithelial connective tissue was present in 5 cases of G2 and 7 cases of G3. According to the 2002 revision of the TNM system, these cases were defined as T1 and the others as Ta. uPAR expression was evaluated with an immunohistochemical technique in 5-microns-thick tissue sections. RESULTS: Difference in the distribution of positive cases in the 4 groups were statistically significant and greatest in G3. Statistically significant differences were also observed between Ta and T1 cases in terms of uPAR intensity. CONCLUSION: Detection of immunoreactivity for uPAR was associated with high grade UP carcinomas. These data indicate that uPAR is potentially an important prognostic factor in bladder carcinoma.

Biomarkers, Tumor↗

PubMed2004

Molecular mechanisms in prostate cancer. A review.

Genetic studies have provided remarkable clues to the causes of prostate cancer (PCa). For example, in addition to the expected role of androgens in facilitating the development of PCa, the possibility that infections might lead to prostate cancer has been raised with the identification of RNASEL and MSR1 as familial prostate cancer genes; that insight will profoundly affect future studies and may ultimately lead to new approaches to the prevention of prostate cancer. The identification of key molecular alterations in prostate cancer cells implicates carcinogen defenses, including GSTP1, growth factor signaling pathways (such as NKX3.1, PTEN and p27) and androgens as critical determinants of the phenotype of PCa cells and defines specific targets for detection, diagnosis and treatment of PCa.

Animals↗

PubMed2004

Renal sarcoma associated with adult polycystic kidney disease. A case report and literature review.

The development of renal cell carcinoma in Adult Polycystic Kidney Disease (APKD) has been reported in the literature; one of the features of renal malignancy in APKD is the difficulty to make a diagnosis, and the majority of cases reported are incidental findings at surgery or autopsy. We report a rare case of renal sarcoma in a patient with APKD. Sarcoma associated with APKD does not seem to have particular biological characteristics when compared with primary renal sarcoma; however the polycystic kidney represents an aggravating circumstance, because of the difficulty in making an early diagnosis of a disease with a poor prognosis.

Humans↗

PubMed2003

Morphological assessment of radical prostatectomy specimens. A protocol with clinical relevance.

The increase in prostate cancer detection has induced a sharp increase in the number of radical prostatectomies Proper examination of radical prostatectomy (RP) specimens by pathologists is critical in determining the need for adjuvant treatment and prediction of patient outcome. The pathology report should include relevant clinical information as well as provide prognostically useful information derived from the macroscopic examination and microscopic evaluation of the RP specimen

Histological Techniques↗

PubMed2003

Subvisual changes in chromatin organization state are detected by karyometry in the histologically normal urothelium in patients with synchronous papillary carcinoma.

This study analyzed the chromatin organization state in histologically normal urothelium in patients with synchronous papillary carcinoma using digital texture analysis. The quantitative evaluation was carried out on hematoxylin and eosin-stained sections from 17 cases of urothelial papillary carcinoma in which a simultaneous biopsy specimen featuring histologically normal urothelium was available. Five bladder biopsy specimens of histologically normal urothelium from patients with prostate pathology in whom cystoscopy revealed a normal bladder mucosa were also analyzed. Karyometry showed that the 17 cases of papillary carcinoma, morphologically classified according to the 1973 World Health Organization scheme, belonged to a continuous spectrum or trend curve spanning grade 1 to grade 3. An abnormal pattern and distribution of the nuclear chromatin was seen in the normal-looking urothelium from the 17 bladders with papillary lesions. When this population was plotted along the trend curve, it occupied an intermediate position between the normal samples and samples from grade 1 carcinoma. When the nuclei were considered individually, the changes were detected only in a subpopulation of nuclei with chromatin alteration pointing toward that seen in grade 1 cases, even though distinct from them. In conclusion, karyometry can detect an abnormal chromatin pattern and distribution in the normal-looking urothelium adjacent to papillary carcinoma. Such alterations correspond to the so-called "malignancy-associated change."

Carcinoma, Papillary↗

PubMed2003

Molecular techniques and prostate cancer diagnostic.

Recent advances in molecular techniques have given the opportunity to assess genomic and proteomic alterations comprehensively and rapidly in routinely acquired tissue samples. In particular, new markers derived from qualitative and quantitative DNA, RNA, and protein analysis have provided additional objective information to supplant and extend the morphologic interpretations and have been increasingly integrated into the final surgical pathology diagnosis. In this review several recently developed molecular techniques are described and illustrated. The focus is on prostate cancer diagnostics, as an example of their application.

Humans↗

PubMed2003

Apolipoprotein E expression in localized prostate cancers.

Although prostate cancer has become the most common solid tumor diagnosed in men and the second leading cause of death due to malignancy, the progression of the disease is still somewhat unpredictable, until it becomes locally advanced or metastatic. The clinical problem to distinguish between dormant and progressive cancers is essential to patient care, as surgical and medical therapies have significant risk of morbidity and disability. Multiple gene expression in prostate cancer was surveyed by differential display cloning between the undifferentiated hormone refractory human prostate cancer cell line PC-3 (highly tumorigenic in nude mice) the hormone responsive LNCaP cell line (weakly tumorigenic in nude mice), and the poorly differentiated DU-145 cell line (moderately tumorigenic). ApoE mRNA was found to be highly expressed only in PC-3 cell-line. We further examined its protein expression by immunohistochemistry in 20 prostatectomy specimens and an association between Gleason score for each sample and ApoE expression was determined. ApoE expression correlates directly with the Gleason score in tissue sections, hormone independence as well as local and distant invasiveness. Prostatic intraepithelial neoplasias (PINs) adjacent to clinically manifested cancer were positive whereas more distant PINs were negative for ApoE. ApoE may represent a marker of more aggressive cells in human prostate cancers.

Aged↗

PubMed2003

Target populations, pathological biomarkers and chemopreventive agents in prostate cancer prevention.

Chemoprevention is the administration of agents to prevent induction of cancer, or to inhibit or delay its progression. In prostatic neoplasia, the time from tumour initiation and progression to invasive carcinoma often begins in men in the fourth and fifth decades of life and extends across decades. This phenomenon represents a unique opportunity to arrest or reverse the process of carcinogenesis with the use of chemopreventive agents. For prostate cancer, as for other cancer targets, development of successful chemopreventive strategies requires suitable cohorts, reliable biomarkers for evaluating chemopreventive efficacy and well-characterised agents. Histopathologists play an important role in prostate chemoprevention. In fact, they define the high-risk groups, recognise the surrogate end markers and evaluate the morphological effects of the agents on the prostate tissue specimens.

Antineoplastic Agents↗

PubMed2002

Improving inter-observer agreement and certainty level in diagnosing and grading papillary urothelial neoplasms: usefulness of a Bayesian belief network.

BACKGROUND AND OBJECTIVE: A Bayesian belief network (BBN), as diagnostic decision support system, enables the processing of our knowledge of histopathology expressed in descriptive terms, words and concepts. The aim of this study was to evaluate the contribution of a BBN in the improvement of inter-observer agreement and certainty level in the diagnosis and grading of papillary urothelial neoplasms. MATERIALS: Inter-observer agreement and certainty level were investigated on 40 cases of non-invasive papillary urothelial neoplasms subdivided according to the WHO 1973 classification. There were 10 urothelial papillomas (UPs), 10 grade 1 papillary carcinomas (G1), 10 grade 2 papillary carcinomas (G2) and 10 grade 3 papillary carcinomas (G3). Five consecutive sessions were held with three observers (RMa, PC and MSt). Sessions A, B and D were based on the morphological evaluation of the specimens with a conventional light microscope only. In sessions C and E, a BBN was used in addition to the microscope. The BBN output was represented by four belief values for four possible diagnostic outcomes. These values ranged from 0.0 to 1.0, with the sum of the belief values being 1.0. Concerning the certainty level, a two-tier system of assessment was adopted in sessions A, B and D: certain versus less certain. In sessions C and E, a belief value equal to or greater than 0.65 was considered as equivalent to "certain". RESULTS: In session A, an all-encompassing or synthetic approach to decision-making was adopted. Agreement with the gold standard was seen in 60% (RMa), 55% (PC) and 65% (MSt) of cases, respectively. The level of subjective confidence was "certain" in 35%, 40% and 35% of cases, respectively. Better agreement-70% (RMa), 68% (PC) and 72% (MSt) of cases-was present in session B where an analytical approach based on the evaluation of a series of morphological features was used. The level of subjective confidence was "certain" in 45%, 50% and 55% of cases, respectively. In session C, where a BBN was utilised, a further increase in degree of agreement with the gold standard was observed, e.g. 85% (RMa), 80% (PC) and 86% (MSt) of cases, respectively. Levels of certainty or belief values were high. Decrease in both the level of agreement-60% (RMa), 62% (PC) and 65% (MSt) of cases-and certainty was seen in session D where the observers were left free to evaluate the cases morphologically without the constrain of either a synthetic or analytical approach. In session E, where the BBN was used again, the percentage of cases in agreement with the gold standard increased to 83% (RMa), 81% (PC) and 84% (MSt), respectively. Increase in certainty or belief was also seen. The difference of the results obtained in the sessions A, B and D with those seen in the BBN-based sessions (C and E) is statistically significant. CONCLUSIONS: Conventional morphological evaluation of papillary urothelial neoplasms is affected by inter-observer variability and, in many instances, by diagnostic uncertainty. The greatest difficulties are found with G1 and G2 cases. Improvement in inter-observer agreement and certainty level can be achieved with a BBN.

Bayes Theorem↗

PubMed2002

Precancerous lesions and conditions of the prostate: from morphological and biological characterization to chemoprevention.

Prostatic intraepithelial neoplasia (PIN) is composed of dysplastic cells with a luminal cell phenotype, expressing the androgen receptor as well as prostate-specific antigen. PIN is characterized by progressive abnormalities of phenotype that are intermediate between normal prostatic epithelium and cancer, indicating impairment of cell differentiation and regulatory control with advancing stages of carcinogenesis. High-grade PIN is considered the most likely precursor of prostatic carcinoma, according to virtually all available evidence. Androgen deprivation decreases the prevalence and extent of PIN and the degree of capillary vascularization (e.g., angiogenesis) in the surrounding stroma via suppression of vascular endothelial growth factor production. Prostatic carcinoma is also likely to arise from precursor lesions other than high-grade PIN such as low-grade PIN, atypical adenomatous hyperplasia, malignancy-associated foci, and atrophy.

Androgens↗

PubMed2002

Evaluation of prognostic factors in radical prostatectomy specimens with cancer.

Prostate cancer (PCa) is a leading cause of morbidity and mortality in males accounting for approximately 30% of all new cases of cancer and approximately 14% of cancer deaths. Despite considerable advances achieved in the ability to detect and treat PCa, there have not been significant corresponding decreases in PCa-related morbidity and mortality. Proper examination of radical prostatectomy specimens by the pathologists is critical in determining the need for adjuvant treatment and prediction of patient outcome. The goal is to tailor the therapeutic approach to the clinical, morphological and molecular features of each patient.

Humans↗

PubMedDate not supplied

Image processing, diagnostic information extraction and quantitative assessment in pathology.

As we enter the information age we hold strong beliefs in the benefits of digital technology applied to pathology: numerical representation offers objectivity. Digital knowledge may indeed lead to significant information discovery, and, processing systems might be designed to allow a true evolution of capabilities. Questions arise whether the methodology underlying quantitative analysis provides the information that we need and whether it is appropriate for some of the problems encountered in diagnostic and prognostic histopathology. While one certainly would not dispute the value of statistical procedures, the clinical needs call for individual patient targeted prognosis.

Diagnostic Imaging↗