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Biomedical subjects

R Mazzucchelli

Publications and source records attributed to R Mazzucchelli.

At least 19 recordsLinked to original sources
PubMed2007

Altered expression of the tetraspanin CD81 on B and T lymphocytes during HIV-1 infection.

CD81 is a member of the tetraspan superfamily and plays a role in immune responses and in hepatitis C virus (HCV) pathogenesis. We analysed CD81 cell surface and mRNA expression in different lymphocytic subpopulations in human immunodeficiency virus (HIV)-1, HCV and dually infected subjects. CD81 cell surface expression was evaluated with fluorescence activated cell sorter (FACS) analysis; mRNA quantification was performed with semiquantitative polymerase chain reaction (PCR). CD81 cell surface expression on CD4(+) T lymphocytes was significantly different by analysis of variance (anova) test (P < 0.001), with reduced expression in HIV-1(+) patients. In B lymphocytes, higher cell surface expression was present in HIV-1, in HCV and in dually infected subjects compared to healthy controls. CD81 expression on B lymphocytes showed a positive correlation with plasma HIV-RNA. CD81 mRNA levels in B lymphocytes were significantly higher in HIV-1(+) patients compared to healthy controls. The potential consequence of the down-regulation of CD81 in CD4(+) cells during HIV-1 infection in conjunction with diverted CD28, CD4 and CD3 expression is the disruption of T cell function. Increased CD81 expression on B lymphocytes might explain the higher prevalence of lymphoproliferative disorders in HIV-1 and HCV infection. Up-regulation of CD81 mRNA on CD4(+) T cells indicates that down-regulation of CD81 occurs at the post-transcriptional/translational level.

Adult↗
PubMed2006

High grade prostatic intraepithelial neoplasia with squamous differentiation.

An unusual variant of prostatic intraepithelial neoplasia with prominent and extensive squamous differentiation is described. The lesion was identified in the transition zone of a 79 year old man with a three year history of increasing urinary obstructive symptoms and a clinical diagnosis of benign prostatic hyperplasia who underwent simple prostatectomy. Two years after surgery, prostatic biopsies showed atrophy and mild chronic inflammation, with no evidence of malignancy. This unusual intraepithelial lesion seems not to have been described before and may represent a new variant of high grade prostatic intraepithelial neoplasia (HGPIN) with squamous differentiation.

Aged↗
PubMed2005

Prognostic role of Fuhrman grade and vascular endothelial growth factor in pT1a clear cell carcinoma in partial nephrectomy specimens.

PURPOSE: Conventional renal cell carcinoma (RCC) is characterized by rich neovascularization and shows a fine vascular network around tumor cells. Nephron sparing surgery has been established as a method of choice or necessity for localized tumors. We investigated the importance of microvessel density (MVD), vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (Flk-1) immunohistochemical expression in a large series of small conventional clear cell renal carcinomas treated with partial nephrectomy and assessed the prognostic value of their expression in terms of patients survival at long-term followup. MATERIALS AND METHODS: A total of 48 patients with a mean age +/- SD of 58.2 +/- 9.5 years who had conventional single RCC were considered. Median tumor diameter was 2.92 +/- 0.82 cm (range 1.3 to 5). Disease was grades 1 to 4 in 15, 29, 2 and 2 patients, respectively. Median followup was 92.9 months (range 17 to 186). RESULTS: Four patients (3.9%) had died of metastatic renal cancer at a median followup of 23.5 months, of whom 1 had a grade 2, 1 had a grade 3 and 2 had grade 4 RCC. Patients with MVD expression higher than the median (44.4 vessels per mm) did not show a significant difference in survival compared to patients with MVD expression lower than the median. Patients with VEGF expression higher than 25% in the histological specimen showed worse survival than patients with VEGF expression lower than 25%. Different Flk-1 expression did not determine a significant difference in survival. On univariate analysis of patient survival in relation to the different considered factors Fuhrman grading was the most important factor for survival. CONCLUSIONS: Our study shows that recurrence and death are possible even in patients with small renal tumors. MVD, VEGF and Flk-1 expression do not depend on tumor size in pT1a RCC. Therefore, to date Fuhrman grading appears to be the only factor predictive of survival even in small RCC. Thus, Fuhrman grading is predictive of mortality. While VEGF is not predictive of survival as a single parameter, based on its percent of expression (lower or higher than 25%) it can determine 2 groups that are different from the prognostic point of view.

Adenocarcinoma, Clear Cell↗
PubMed2005

Basal cell hyperplasia and basal cell carcinoma of the prostate: a comprehensive review and discussion of a case with c-erbB-2 expression.

Prostatic basal cell proliferations range from ordinary basal cell hyperplasia (BCH) to florid basal cell hyperplasia to basal cell carcinoma. The distinction between these forms of BCH, including the variant with prominent nucleoli (formerly called atypical BCH), and basal cell carcinoma depends on morphological and immunohistochemical criteria and, in particular, on the degree of cell proliferation. In florid BCH, the proliferation index is intermediate between ordinary BCH and basal cell carcinoma. Immunohistochemistry is also useful for identifying the cell composition of the basal cell proliferations, including the basal cell nature of the cells, their myoepithelial differentiation, and c-erbB-2 oncoprotein expression. Based on the information derived from the literature and on the appearance and follow up of the case presented here, florid BCH might represent a lesion with an intermediate position between ordinary BCH and basal cell carcinoma. However, criteria useful for the identification of those cases with a true precursor nature are not available. In general, basal cell carcinoma is seen as a low grade carcinoma. The immunohistochemical expression of the c-erbB-2 oncoprotein, similar to that seen in breast cancer, might have therapeutic importance.

Aged↗
PubMed2004

Assessment and reporting of pathological findings of penile specimens.

The correct assessment of penile specimens may provide clinically relevant diagnostic and prognostic data. This protocol is intended to assist pathologists in providing useful information to the clinicians and urologists and to uniform the examination of the penis by a standardized approach.

Carcinoma, Squamous Cell↗
PubMed2003

Elevated E-cadherin and alpha/beta-catenin expression after androgen deprivation therapy in prostate adenocarcinoma.

The histological patterns of anti-androgen-treated prostate adenocarcinoma mimic high grade tumors classified according to the widely used Gleason scoring system. However, the biological characteristics of anti-androgen treated carcinoma are largely unknown. E-cadherin, alpha-catenin, and beta-catenin adhesion molecules are down-regulated in pharmacologically untreated high grade prostate carcinoma. In this study, we used immunohistochemical techniques to investigate their expression in twenty acinar adenocarcinomas after anti-androgen therapy in prostatectomy specimens. After adrogen ablation therapy, expression of all these adhesion molecules was higher than that of pretreatment biopsies of the same patient group and high grade matched untreated controls. These results emphasize the inaccuracy of the Gleason score for anti-androgen-treated prostate adenocarcinoma and the more differentiated phenotype of prostate adenocarcinoma after anti-hormonal therapy.

Adenocarcinoma↗
PubMed2003

Classification and grading of the non-invasive urothelial neoplasms: recent advances and controversies.

The classification and grading of the non-invasive, intraepithelial neoplasms of the urothelium are based on the morphological pattern of growth-that is, papillary or flat (and endophytic)-and on their degree of architectural and cytological 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.

Carcinoma in Situ↗
PubMed2003

Mucinous adenocarcinoma with superficial stromal invasion and villous adenoma of urachal remnants: a case report.

This report describes a case of mucinous adenocarcinoma with superficial stromal invasion and villous adenoma originating in the dome of the urinary bladder. Although no urachal remnants were identified, the location suggested urachal derivation. Only two previous cases of urachal adenocarcinoma with features of early stromal invasion associated with a villous tumour have been described.

Adenocarcinoma, Mucinous↗
PubMed2002

Predictive factors in prostate needle biopsy.

Prostate cancer (PCa) is a leading cause of morbidity and mortality in men, 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 prostate biopsy specimens by pathologists is critical in determining the type of treatment and predicting patient outcome. The goal is to tailor the therapeutic approach to the clinical, morphological and molecular features of each patient.

Adenocarcinoma↗
PubMed2002

Effects of complete androgen blockade for 12 and 24 weeks on the pathological stage and resection margin status of prostate cancer.

AIMS: To compare the pathological stage and surgical margin status in patients undergoing either immediate radical prostatectomy or 12 and 24 weeks of neoadjuvant hormonal treatment (NHT) in a prospective, randomised study. METHODS: Whole mount sections of 393 radical prostatectomy specimens were evaluated: 128 patients had immediate surgery, 143 were treated for 12 weeks and 122 for 24 weeks with complete androgen blockade. RESULTS: Histopathology revealed organ confined tumours in 40.4% of patients with clinical stage B disease in the immediate surgery group, whereas 12 and 24 weeks of NHT increased the number of organ confined tumours to 54.6% and 64.8%, respectively. Among patients with clinical stage C tumours, pathological staging found organ confined disease in 10.4%, 31.4%, and 61.2% in the immediate surgery, 12 weeks of NHT, and 24 weeks of NHT groups, respectively. Preoperative NHT caused a significant decrease in positive margins both in patients with clinical stage B and C disease. The extent of margin involvement was not influenced by preoperative treatment. CONCLUSIONS: Neoadjuvant androgenic suppression is effective in reducing both the pathological stage and the positive margin rate in patients with stage B and C prostatic cancer undergoing radical surgery. Some beneficial effects are evident in those patients treated for 24 weeks, and it is reasonable to assume that the optimal duration of NHT is longer than three months.

Aged↗
PubMed2002

Changes produced in the urothelium by traditional and newer therapeutic procedures for bladder cancer.

A handful of traditional and newer therapeutic procedures, such as chemotherapy, immunotherapy, radiotherapy, photodynamic and laser treatment, and gene therapy, are used to treat epithelial malignancies of bladder origin. These treatment modalities, used either intravesically or systemically, produce morphological changes in the urothelial mucosa that can be mistaken for carcinoma. The pathologist must be able to separate toxic and drug related alterations from tumour related changes. The clinical history is usually invaluable in this assessment.

Antineoplastic Agents↗
PubMed2002

Prostatic intraepithelial neoplasia and prostate cancer.

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 which are intermediate between normal prostatic epithelium (NP) 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 (PCa), 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 the suppression of vascular endothelial growth factor (VEGF) production. It is likely that PCa might also arise from precursor lesions other than high-grade PIN (low-grade PIN, atypical adenomatous hyperplasia, malignancy-associated foci, and atrophy).

Androgen Antagonists↗
PubMed2001

Effect of complete androgen blockade on pathologic stage and resection margin status of prostate cancer: progress pathology report of the Italian PROSIT study.

OBJECTIVES: To compare the pathologic stage and surgical margin status in patients undergoing either immediate radical prostatectomy or surgery preceded by 3 or 6 months of neoadjuvant hormonal treatment (NHT) in a prospective, randomized study. METHODS: Four hundred thirty-one men with prostate cancer were enrolled in the Italian randomized prospective PROSIT study. The whole-mount sectioning technique was used. By May 1999, the reviewing pathologist had evaluated 303 specimens. One hundred seven patients were untreated before radical prostatectomy was performed, and 114 and 82 patients had been treated for 3 and 6 months, respectively, with complete androgen blockade. RESULTS: Pathologic organ-confined disease was found in 63.1% of patients with clinical Stage B disease treated with 6 months of NHT versus 61.0% after 3 months of NHT and 37.5% after immediate surgery. Among patients with clinical Stage C tumors, pathologic staging found organ-confined disease in 62.5%, 32.1%, and 11.1% of patients after 6 months of NHT, 3 months of NHT, and immediate surgery, respectively. Three months of NHT produced a significant increase in negative margins both in patients with clinical Stage B and C disease, but the addition of another 3 months of treatment did not significantly improve this result. A lower degree of benefit was observed in patients with clinical Stage C tumors. CONCLUSIONS: This study shows that complete androgen blockade before surgery is beneficial in men with clinical Stage B disease. The effects are more pronounced after 6 months of NHT than after 3 months.

Aged↗
PubMed2001

Assessment of radical prostatectomy specimens and diagnostic reporting of pathological findings.

Proper examination of radical prostatectomy (RP) specimens from patients with prostate cancer (PCa) is critical for determining the need for adjuvant treatment and for predicting the outcome. The first step in the examination is represented by the assessment of the specimens. This includes proper fixation in formalin and whole-mount sectioning. The second step is related to the diagnostic reporting of pathological findings. This includes the evaluation of tissue features such as Gleason grade, stage and margin status. These three parameters, together with serum prostate-specific antigen (PSA) determination, are predictive factors whose prognostic role has been demonstrated in several studies.

Adenocarcinoma↗
PubMed2000

Vascular endothelial growth factor expression and capillary architecture in high-grade PIN and prostate cancer in untreated and androgen-ablated patients.

BACKGROUND: Recent studies have demonstrated that angiogenesis is a potent prognostic indicator for patients with prostate cancer (PCa) and have pointed out that the evaluation of vascular endothelial growth factor (VEGF) is useful in assessing the angiogenic phenotype in PCa. The aim of the study was to investigate immunohistochemically the expression of VEGF and its correlation with the pattern of capillary architecture in prostate cancer and high-grade prostatic intraepithelial neoplasia (PIN), in untreated and androgen-ablated patients. METHODS: Forty-five patients who underwent radical prostatectomy (RP) for localized prostate carcinoma were recruited for this study. The study population included two groups: 35 patients who did not receive chemo-, hormone, or radiation therapy before surgery, and 10 patients who were under complete androgen blockade (CAB) for 3 months at time of surgery. VEGF was examined by immunohistochemistry, and its tissue expression was compared with the pattern of capillary architecture evaluated by immunostaining the endothelial antigen CD34. The relationship of VEGF expression to chromogranin A-positive (e.g., neuroendocrine) cells was investigated. RESULTS: In normal tissue, the intensity of the VEGF immunoreactivity in the cytoplasm of secretory cells ranged from negative to low. Very few basal cells stained for VEGF. All prostate cancer specimens stained positively, the intensity of the immunoreaction ranging from low to strong and being correlated with the Gleason score. Strongly positive VEGF immunoreactivity was detected in vascular endothelial cells and in stromal cells surrounding blood vessels. Two discrete immunostaining patterns were observed in high-grade PIN. VEGF expression of low-to-moderate intensity was defined as pattern A. The other, characterized by a strong cytoplasmic immunoreaction similar to that of poorly differentiated tumors, was defined as pattern B. The capillary architecture in high-grade PIN with pattern A was similar to the orderly vascular network seen in normal prostates, whereas in the pattern B it had the characteristics of microvessels usually seen in PCa. The degree of vascularization in the stroma adjacent to intensely VEGF-stained cells (neuroendocrine phenotype) was higher than that noted in association with secretory cells. CAB before surgery downregulated the expression of VEGF and decreased the degree of vascularization, except in the cell areas with neuroendocrine (NE) features. CONCLUSIONS: Our immunohistochemical results indicate that significant levels of VEGF are present in prostate cancer and in a population of PIN lesions, expression being highest in association with NE cells. VEGF expression is downregulated by hormonal manipulation, except in the population of NE cells.

Adenocarcinoma↗
PubMed2000

Morphometric index of adult renal cell carcinoma. Comparison with the Fuhrman grading system.

Various grading systems have been proposed for renal cell carcinoma (RCC), using nuclear, cytoplasmic, and architectural features. The available evidence suggests that nuclear grading is a better prognostic indicator than other types of grading schemes. Nuclear morphometry may still improve the correlation of the nuclear grading with survival, however, because observer consistency is lacking in the subjective grading of RCC. The aim of this study was to investigate morphometrically whether RCC cases show a continuous spectrum of nuclear changes or whether there are discrete groups of cancer that correspond to the four Fuhrman grades. Karyometry was performed on 5- microm-thick, haematoxylin- and eosin-stained sections from 60 cases of conventional (clear cell) RCC. The analysis also included the evaluation of normal renal tissue (proximal tubules) adjacent to cancer. In each case the difference between the value of the cancer and the corresponding normal epithelium was calculated to represent, quantitatively, the degree of similarity between the tumour tissue and the internal normal control. When the differences were sorted into ascending order, a steady increase in values was observed for both the nuclear and the nucleolar features. A monotonic trend was evident for the differences in the mean maximum nuclear diameter and mean nucleolar area. When the differences between the values in the cancer and in the corresponding normal epithelium of these two features were summed up, the method resulted in a continuous variable, or nuclear morphometric index, related to the degree of deviation of each individual RCC from its internal normal control. The lowest index values were observed in of Fuhrman grade I cases, whereas values ranging from 2.679 to 5.422 were associated with cases graded II. Values equal to or higher than 5.951 were seen in the cases assigned to either grade III or grade IV. Partial overlap was present between the index values in grades III and IV. The RCC cases can be represented by a continuous index that corresponds to the morphological grading based on the Fuhrman scheme. This study shows that the index may be useful in supplementing the pathologist's grading. This issue can be further addressed with follow-up studies.

Adult↗