Biomedical subjects

Rodolfo Montironi

Publications and source records attributed to Rodolfo Montironi.

At least 37 records · Page 2Linked to original sources

PubMed2006

Multilocular cystic renal cell carcinoma : a report of 45 cases of a kidney tumor of low malignant potential.

The 2004 World Health Organization (WHO) classification of kidney tumors recognizes multilocular cystic renal cell carcinoma (MCRCC) as a rare variant of clear cell renal cell carcinoma with a good prognosis. Available information on its clinical significance is limited. The study cohort included 45 MCRCC cases classified according to 2004 WHO criteria obtained through a multi-institutional international search. Most patients had unilateral MCRCC with no side predominance that was found incidentally; 62% were men, but women had tumors at an earlier age (P = .385). MCRCC occurred slightly more often in men than in women (1.7:1). At diagnosis, 82% of patients had stage T1 and 16%, stage T2; 1 patient had stage T3. The Fuhrman grade was 1 (62%) or 2 (38%), with smaller tumors (<or=4 cm) most likely Fuhrman grade 1 (P = .911). All 45 patients were alive with no evidence of disease at mean follow-up of 66.1 months, confirming an extremely good prognosis after surgery and a 5-year disease-specific survival rate of 100%. To rename this tumor as multilocular cystic renal cell neoplasm of low malignant potential might help urologists approach the patients conservatively.

Adult↗

PubMed2006

Cyclin E as molecular marker in the management of breast cancer: a review.

Over the past decade numerous molecular markers have been identified that may play a role in breast carcinogenesis and prognosis. The most commonly used markers in clinical practice are the estrogen receptor, progesterone receptor and HER-2/neu. Recent studies found cyclin E to be a promising prognostic indicator in breast cancer and examined its potential as a target for therapy. Further studies demonstrated that cyclin E levels were periodic during the cell cycle, with levels of protein peaking in the G1 phase. This peak in cyclin E levels also correlated with maximum enzymatic function of the cyclin E-cdk2 complex, suggesting a critical role of cyclin E in regulating G1 to S-phase transition. Studies examining the relevance of cyclin E alterations in breast cancer have shown gene amplifications in some breast cancer cell lines, data that provide strong support for the role of cyclin E in breast carcinogenesis. It is believed that the most significant cyclin E alteration is post-translational cleavage of full-length cyclin E into low molecular weight forms that are hyperactive compared to the 50-kDa, full-length protein and correlate with increasing stage and grade of breast cancer. The role of cyclin E in the prognosis and therapy of breast cancer is reviewed according to recent publications.

Biomarkers↗

PubMed2006

Intratubular germ cell neoplasia of unclassified type.

Intratubular germ cell neoplasia of unclassified type (IGCNU) is the precursor lesion of adult testicular germ cell invasive tumors. Primordial germ cells (PGCs) are recognized as the cells of origin of testicular germ cell tumors (TGCTs) because of the genetic and phenotypic characteristics analyzed. The most important risk factors responsible for abnormal development of PGCs are environmental, including the testicular dysgenetic syndromes that generate a better microenvironmentfor survival of IGCNU cells, an abnormal relationship with Sertoli cells, and an abnormal hormonal exposure at the time of testicular differentiation in utero. Furthermore, a familial TGCT susceptibility gene (TGCT1), localized at Xq27, is associated with a higher risk for bilateral tumors and possibly cryptorchidism. The normal tetraploid pattern and the consequent genomic instability of germinal cell DNA are considered sufficient per se for neoplastic transformation. The altered expression of oncogenes and suppressor genes due to nonrandom chromosomal numerical aberrations are involved in the development of IGCNU. Some of these genes are considered responsible for bilaterality, while other genes characterize the similarity between IGCNU cells and PGCs or are involved in the neoplastic transformation, histotype differentiation, and invasivity. In spite of the monomorphic seminomatous appearance of cells in IGCNU, it is becoming increasingly evident that they hide an intrinsic heterogeneity capable of committing neoplastic cells to an embryonal and pluripotent development associated or not with a seminomatous phenotype.

Germ Cells↗

PubMed2006

Soft tissue tumors of the penis: a review.

Penile soft tissue tumors comprise 5% of tumors at this site and most have been reported as isolated case reports. The purpose of this review is to aid the practicing surgical pathologist in distinguishing penile soft tissue tumors, such as sarcomatoid squamous cell carcinoma, from other prognostically and therapeutically important entities in the differential diagnosis. Clinical presentation, management, prognosis and factors influencing behavior are reviewed. The immunohistochemical profiles and salient morphologic clues that may help distinguish penile spindle cell tumors from sarcomatoid carcinomas are evaluated. Soft tissue tumors of the penis may be classified as benign or malignant, as superficial or deep and in terms of age at presentation. All are rare. The most common benign soft tissue tumors that affect the penis are vascular neoplasms, followed by tumors of neural, myoid and fibrous origin. Among reported cases, the most frequent malignant penile soft tissue tumors are Kaposi sarcoma and leiomyosarcoma. Correctly diagnosing penile soft tissue tumors is imperative, because the biologic behavior and the clinical management of these neoplasms vary considerably. Distinguishing sarcomas from sarcomatoid carcinoma and melanoma is particularly important. Accurate diagnosis is best facilitated by consideration of all available aspects of the case, including clinical information, histopathologic findings and immunohistochemical results.

Humans↗

PubMed2006

Carcinogenesis and the hypothesis of phylogenetic reversion.

Chemoprevention must target early molecular events involved in malignant transformation. The sequence of events leading from a normally functioning interphase cell to an uncontrolled tumor cell is only partially understood, impeding systematic design of chemopreventive agents. The respective roles of mutagenic and epigenetic mechanisms have not been definitively established. Also, traditional models do not appear to incorporate cellular response to events leading to carcinogenesis. A perspective on system response offered by complexity science elucidates the roles of feedback and control in maintaining functional stability during carcinogenesis. Carcinogenesis is seen as a process of epigenetic redifferentiation resulting in a cell behaving like an archetypal karyocyte free of growth restraints (phylogenetic reversion). Genes that evolved during the development of multicellular organisms, restraining uncontrolled growth and regulating intercell communication may be systematically silenced during carcinogenesis. The formation of heterochromatin, which results in epigenetic silencing by hypermethylation in CpG-dense islands, finds expression in the nuclear chromatin pattern. Karyometry is an integrating biomarker of chromatin pattern information that accommodates the possibility of multiple, differently ordered pathways and provides exquisite sensitivity, allowing detection of very early transformation events. Its use can monitor the impact of chemopreventive agents on the earliest events in progression to cancer.

Animals↗

PubMed2005

Current practice of Gleason grading of prostate carcinoma.

The Gleason grading system remains one of the most powerful prognostic factors in prostate cancer and is the dominant method around the world in daily practice. It is based solely on the glandular architecture performed at low magnification. The Gleason grading system should be performed in needle core biopsies and radical prostatectomy specimens where it shows a reasonable degree of correlation between both specimens, and most importantly, it remains vital in the treatment decision-making process. This review summarizes the current status of Gleason grading in prostate cancer, incorporating recent proposals for the best contemporary practice of prostate cancer grading.

Humans↗

PubMed2005

Identification of clinical prognostic factors in patients with unknown primary tumors treated with a platinum-based combination.

OBJECTIVE: The aim of this study was to evaluate patient and tumor characteristics in 102 patients with unknown primary tumors (UPT) prospectively treated with a combination of carboplatin, doxorubicin, and etoposide, to identify clinical variables predictive of response and survival. PATIENTS AND METHODS: The association between clinical characteristics and outcome was evaluated by univariate and multivariate analysis: chi(2) test and logistic regression analysis were used to study variables predictive of response, and survival analysis, comparison of survival curves and Cox multiple regression analysis to study variables predictive of survival. RESULTS: We obtained 26.5% objective responses (95% confidence interval: 18.2-36.1%) and a median survival of 9 months (95% confidence interval: 7-11 months). Several variables were associated with response to treatment and survival at univariate analysis. At multivariate analysis the number of tumor sites, bone/visceral involvement and epithelial tumor markers were significantly predictive of response; presence of pain, serum alkaline phosphatase, carboplatin AUC and response to treatment were significantly associated with survival. CONCLUSIONS: The identification of variables that can predict prognosis and response to treatment in patients with UPT may be useful to offer aggressive treatment to sensitive subsets of patients and provide therapeutic alternatives to those with a low probability of benefiting from standard treatment. In our patients the use of carboplatin AUC higher than 6 and response to treatment were the most important factors associated with prognosis, together with presence of pain and serum alkaline phosphatase. However, larger series and identification of new disease markers are necessary to better define predictive and prognostic variables in UPT patients.

Adult↗

PubMed2005

Nonapical and cytoplasmic expression of interleukin-8, CXCR1, and CXCR2 correlates with cell proliferation and microvessel density in prostate cancer.

PURPOSE: We characterized interleukin-8 (IL-8) and IL-8 receptor expression (CXCR1 and CXCR2) in prostate cancer to address their significance to this disease. EXPERIMENTAL DESIGN: Immunohistochemistry was conducted on 40 cases of human prostate biopsy containing histologically normal and neoplastic tissue, excised from patients with locally confined or invasive androgen-dependent prostate cancer, and 10 cases of transurethral resection of the prostate material from patients with androgen-independent disease. RESULTS: Weak to moderate IL-8 expression was strictly localized to the apical membrane of normal prostate epithelium. In contrast, membranous expression of IL-8, CXCR1, and CXCR2 was nonapical in cancer cells of Gleason pattern 3 and 4, whereas circumferential expression was present in Gleason pattern 5 and androgen-independent prostate cancer. Each of IL-8, CXCR1, and CXCR2 were also increasingly localized to the cytoplasm of cancer cells in correlation with advancing stage of disease. Cytoplasmic expression (but not apical membrane expression) of IL-8 in Gleason pattern 3 and 4 cancer correlated with Ki-67 expression (R = 0.79; P < 0.001), cyclin D1 expression (R = 0.79; P < 0.001), and microvessel density (R = 0.81; P < 0.001). In vitro studies on androgen-independent PC3 cells confirmed the mitogenic activity of IL-8, increasing the rate of cell proliferation through activation of both CXCR1 and CXCR2 receptors. CONCLUSIONS: We propose that the concurrent increase in IL-8 and IL-8 receptor expression in human prostate cancer induces autocrine signaling that may be functionally significant in initiating and promoting the progression of prostate cancer by underpinning cell proliferation and angiogenesis.

Aged↗

PubMed2005

Association of human herpesvirus type 6 DNA with human bladder cancer.

We examined the presence of human herpesvirus type 6 (HHV6) DNA in a series of 74 bladder carcinomas from a Mediterranean population to elucidate their possible role as cofactor in the development of bladder cancer with or without associated human papillomavirus (HPV) infection. HHV-6 type B DNA was present in 5 men (6.8%) out of the 74 tumors investigated; two of them had associated HPV-16 DNA in the same specimen. In one case that had associated urothelial carcinoma in situ, both HHV-6B and HPV-16 DNA were present. In conclusion, the low incidence of HHV-6B in bladder cancer and the ubiquitous nature of HHV-6 infection are more consistent with a bystander role rather than cofactor in the oncogenesis of bladder cancer.

Adult↗

PubMed2005

Incidentally detected prostate cancer in cystoprostatectomies: pathological and morphometric comparison with clinically detected cancer in totally embedded specimens.

There are limited data regarding the pathological features of incidentally detected prostate cancer. Examination of cystoprostatectomy specimens obtained during bladder cancer treatment affords a unique opportunity to examine incidentally detected prostate cancer and determine its relationship with clinically detected prostate cancer obtained during radical prostatectomy. We compared the pathological findings of incidentally detected prostate cancer in 132 consecutive cystoprostatectomy specimens from patients treated for bladder cancer with a consecutive series of 228 radical prostatectomy specimens from patients treated for prostate cancer. All specimens were totally embedded and whole-mounted. Karyometry was evaluated in select subsets of patients from the study groups. Incidentally detected cancer was found in 42% of cystoprostatectomy specimens, and the cancers were of lower Gleason score and lower pathological stage with fewer positive surgical margins than in clinically detected cancers in age-matched radical prostatectomies. High-grade prostatic intraepithelial neoplasia (PIN) was present in 82% of radical prostatectomy specimens, in 70% of cystoprostatectomies with incidentally detected prostate cancer, and in 54% of cystoprostatectomies without prostate cancer. Mean nuclear and nucleolar area was lower in incidentally detected cancer and PIN when compared with clinically detected cancer and PIN, respectively, similar to the results with proliferative indices. We conclude that incidentally detected cancer is less aggressive than clinically detected cancer.

Humans↗

PubMed2005

Prognostic and predictive factors in prostate cancer: historical perspectives and recent international consensus initiatives.

An understanding of prognosis in cancer medicine is important for patient care, research and cancer control programs. In prostate cancer, prognostic (predictive) factors are particularly important given the marked heterogeneity of this disease at clinical, morphologic and biomolecular levels. Clinical stage and histologic grade have historically played major roles in defining heterogeneity in prostate cancer. More recently, serum prostate-specific antigen measurement has assumed a significant prognostic role. Over the last two decades there has been an explosion of research into biomarkers, many of which have been purported to have prognostic significance. In this paper we present an overview of the various consensus initiatives that have transpired over the last dozen years. Criteria for evaluating prognostic factors and classifications of predictive factors have emerged that have proven useful and advanced our understanding of the biology of prostate cancer. The results of these consensus initiatives form a foundation on which the current international consultation on prognosis (prediction) in prostate cancer is built. Advances in our understanding of the new and promising prognostic factors will require a more rigorous evidence-based approach to the analysis of published studies. Furthermore, appropriate mathematical models for the analysis of the multiple factors that influence a prognostic system will have to be employed.

Adenocarcinoma↗

PubMed2005

Prognostic and predictive factors and reporting of prostate carcinoma in prostate needle biopsy specimens.

The information provided in the surgical pathology report of a prostate needle biopsy of carcinoma has become critical in the subsequent management and prognostication of the cancer. The surgical pathology report should thus be comprehensive and yet succinct in providing relevant information consistently to urologists, radiation oncologists and oncologists and, thereby, to the patient. This paper reflects the current recommendations of the 2004 World Health Organization-sponsored International Consultation, which was co-sponsored by the College of American Pathologists. It builds on the existing work of several organizations, including the College of American Pathologists, the Association of Directors of Anatomic and Surgical Pathologists, the Royal Society of Pathologists, the European Society of Urologic Pathology and the European Randomized Study of Screening for Prostate Cancer.

Biomarkers, Tumor↗

PubMed2005

Prognostic factors and reporting of prostate carcinoma in radical prostatectomy and pelvic lymphadenectomy specimens.

This paper, based on the activity of the Morphology-Based Prognostic Factors Committee of the 2004 World Health Organization-sponsored International Consultation, describes various methods of handling radical prostatectomy specimens for both routine clinical use and research purposes. The correlation between radical prostatectomy findings and postoperative failure is discussed in detail. This includes issues relating to pelvic lymph node involvement, detected both at the time of frozen section and in permanent sections. Issues of seminal vesicle invasion, including its definition, routes of invasion and relationship to prognosis, are covered in detail. The definition, terminology and incidence of extra-prostatic extension are elucidated, along with its prognostic significance relating to location and extent. Margins of resection are covered in terms of their definition, the etiology, incidence and sites of positive margins, the use of frozen sections to assess the margins and the relationship between margin positivity and prognosis. Issues relating to grade within the radical prostatectomy specimen are covered in depth, including novel ways of reporting Gleason grade and the concept of tertiary Gleason patterns. Tumor volume, tumor location, vascular invasion and perineural invasion are the final variables discussed relating to the prognosis of radical prostatectomy specimens. The use of multivariate analysis to predict progression is discussed, together with proposed modifications to the TNM system. Finally, biomarkers to predict progression following radical prostatectomy are described, including DNA ploidy, microvessel density, Ki-67, neuroendocrine differentiation, p53, p21, p27, Bcl-2, Her-2/neu, E-cadherin, CD44, retinoblastoma proteins, apoptotic index, androgen receptor status, expression of prostate-specific antigen and prostatic-specific acid phosphatase and nuclear morphometry.

Biomarkers, Tumor↗

PubMed2005

Gleason grading of prostate cancer in needle biopsies or radical prostatectomy specimens: contemporary approach, current clinical significance and sources of pathology discrepancies.

The Gleason grading system is a powerful tool to prognosticate and aid in the treatment of men with prostate cancer. The needle biopsy Gleason score correlates with virtually all other pathological variables, including tumour volume and margin status in radical prostatectomy specimens, serum prostate-specific antigen levels and many molecular markers. The Gleason score assigned to the tumour at radical prostatectomy is the most powerful predictor of progression after radical prostatectomy. However, there are significant deficiencies in the practice of this grading system. Not only are there problems among practising pathologists but also a relative lack of interobserver reproducibility among experts.

Biopsy, Needle↗

PubMed2005

The 2004 WHO classification of bladder tumors: a summary and commentary.

The key points of the latest World Health Organization (WHO) classification of non-invasive urothelial tumors are the following: the description of the categories has been expanded to improve their recognition; a tumor with particularly good prognosis (papillary urothelial neoplasm of low malignant potential) no longer carries the label of 'cancer'; it avoids the use of ambiguous grading such as grade 1/2 or 2/3 (as done in the 1973 WHO classification); the group of noninvasive high-grade carcinoma is large enough to virtually contain all those tumors having biological properties similar to those seen in invasive urothelial carcinoma, and a similarly high level of genetic instability. This scheme is meant to replace the 1973 WHO classification, but the use of both the 1973 and the latest WHO classifications is recommended until the latter is sufficiently validated.

Carcinoma, Transitional Cell↗

PubMed2005

Atypical adenomatous hyperplasia (adenosis) of the prostate: DNA ploidy analysis and immunophenotype.

Atypical adenomatous hyperplasia (AAH) of the prostate is a microscopic proliferation of small acini that may be mistaken for adenocarcinoma. Although some data suggest that AAH is associated with adenocarcinoma arising in the transition zone, the clinical significance of this lesion is uncertain. Therefore we studied the DNA ploidy pattern and immunophenotype of AAH as compared with nodular hyperplasia and well-differentiated adenocarcinoma in 23 formalin-fixed, paraffin-embedded, whole-mounted retropubic prostatectomies. Representative sections were immunostained for keratin 34beta-E12, chromogranin, bcl-2, c-erbB-2, ki67-MIB1, and factor VIII (microvessel density). DNA ploidy was determined by image analysis and Feulgen-stained sections. There were rare scattered immunoreactive cells for chromogranin, bcl-2, and c-erbB-2 in nodular hyperplasia and AAH (mainly in the basal cell compartment) and in carcinoma. The ki67-MIB1 labeling index was different between nodular hyperplasia and AAH (p<0.001) and carcinoma (p=0.003) but not between AAH and carcinoma (p=0.203). Microvessel density was different between AAH and carcinoma (p=0.001) but not between nodular hyperplasia and AAH (p=0.105) or carcinoma (p=0.0820). All foci of nodular hyperplasia, AAH, and carcinoma were diploid. Ploidy status and our selected panel of antibodies did not discriminate among these 3 entities reliably.

Adenocarcinoma↗

PubMed2005

Chromosomal abnormalities in macroscopically normal urothelium in patients with bladder pT1 and pT2a urothelial carcinoma: a fluorescence in situ hybridization study and correlation with histologic features.

OBJECTIVE: To analyze chromosomal abnormalities in macroscopically normal urothelium in patients with bladder pT1 and pT2a urothelial carcinoma and correlate the changes with histologic features. STUDY DESIGN: Cytologic touch preparations of the tumors and of the adjacent and distant urothelium were obtained from 8 bladders with urothelial carcinoma. Fluorescence in situ hybridization (FISH) was used to detect abnormalities of chromosomes 3, 7, 9 and 17 and of the 9p21 locus. RESULTS: The macroscopically normal urothelium adjacent to and distantfrom neoplastic foci was either normal looking microscopically or showed histologic changes ranging from hyperplasia to dysplasia and carcinoma in situ. FISH analysis detected chromosome gains and 9p21 deletion similar to those present in the urothelial carcinoma even though the percentage of altered nuclei was lower, especially in hyperplasia. The microscopically normal urothelium showed minor abnormalities in terms of gain for all the chromosomes investigated. CONCLUSION: Even though urothelium looks normal from the macroscopic point of view, it frequently harbors histologic changes and chromosomal abnormalities. These findings are of clinical significance since they might represent genetic alterations involved in recurrence and/or progression of urothelial carcinoma.

Aged↗

PubMed2005

Prostate cancer outcome: epidemiology and biostatistics.

Substantial gaps exist in our ability to accurately predict prognosis, and these gaps limit our understanding of the complex mechanisms that contribute to the greatest cancer epidemic of our time, prostate cancer. This review addresses contemporary epidemiologic and biostatistical issues in prostate cancer. It covers the science of outcome prediction and biomarker evaluation, recognition of the need to combine biomarkers to improve the accuracy of our outcome estimates and an analysis of current outcome assessment methods, including the TNM staging system and multivariate regression models. The simplicity and intuitive ease of the current TNM staging system must be balanced against its serious limitations in predictive accuracy and its loss of clinical utility. Statistical regression methods are required as we move to the new era of personalized medicine. We must implement statistical approaches that integrate the new molecular biomarkers with existing prognostic biomarkers to accurately predict which patients require treatment and to determine the optimal therapy.

Biomarkers, Tumor↗