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Histopathology 09/2009; 55(2):230-2. · 3.08 Impact Factor
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Medicina Clínica 04/2009; 132(9):351-8. · 1.38 Impact Factor
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ABSTRACT: OBJECTIVES To evaluate alpha, beta and gamma-catenin expression in upper urinary tract urothelial tumours (UUTC) and determine their value as prognostic factors; to investigate the correlation between the catenin complex and the AKT pathway. PATIENTS AND METHODS We retrospectively analysed 114 consecutive patients treated at our institution from 1990 to 2004; the mean follow-up was 54 months. Tumour samples were available from 70 patients, and included in tissue microarrays for immunohistochemical analysis. The antibodies used were anti-alpha, -beta and gamma-catenin, and antiphospho-AKT. The prognostic value of the expression of these molecules was analysed using tumour progression and cancer-specific survival as end-points. RESULTS Of the 114 patients, 27% developed tumour progression; the cancer-specific and overall survival were 77% and 60.6%, respectively. Abnormal alpha, beta and gamma-catenin expression was found in 44 (63%), 22 (31%) and 28 (41%) patients, respectively; the abnormal catenin expression patterns correlated with each other. Positive cytoplasm phospho-AKT expression was found in 27 (39%) patients. Three of them were found to have cytoplasmic beta-catenin accumulation and none of them nuclear expression. beta-catenin expression was the only one that was an independent marker of tumour progression, with a hazard ratio (95% confidence interval) of 3.1(1.2-8.6), together with grade (7.1, 1.2-55.8) and stage (4.6, 2.1-10). In the cancer-specific survival analysis, again beta-catenin was an independent prognostic factor (3.4, 1-11.5) together with stage (4.6, 2.2-9.8). CONCLUSIONS The loss of the normal membrane beta-catenin expression constitutes an independent factor of tumour progression and cancer-specific survival. Our data suggest that the AKT/GSK3beta/beta-catenin signalling pathway is not activated in the UUTC carcinogenesis.
BJU International 02/2009; 104(1):100-6. · 2.84 Impact Factor
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ABSTRACT: Appropriate interpretation of a frozen section has a relatively high specificity and sensitivity for the diagnosis of infection when septic loosening of a prosthesis is suspected. However, its usefulness for predicting the presence of microorganisms at the time of reimplantation after hip resection arthroplasty for the treatment of infection is not well defined. The aim of the present study was to evaluate the usefulness of histological analysis in this situation.
From January 2002 to February 2006, a total of twenty-one patients underwent reimplantation after hip resection arthroplasty for the treatment of infection. Histological studies and cultures of specimens of periprosthetic tissue that had been obtained at the time of reimplantation were retrospectively reviewed. The results of culture were considered positive when the same microorganism was isolated in at least two samples. Two histological criteria were used to diagnose infection: (1) Criterion A (the Feldman criterion), defined as the presence of at least five neutrophils per high-power field (x400) in at least five separate microscopic fields and (2) Criterion B (the Athanasou criterion), defined as the presence of at least one neutrophil per high-power field (x400), on average, after examination of ten microscopic fields. The sensitivity, specificity, positive predictive value, and negative predictive value of each of these criteria were calculated with use of microbiological results as the gold standard for defining infection.
Seven of the twenty-one patients had a positive result on culture, and the most common microorganism was coagulase-negative staphylococcus. The sensitivity, specificity, positive predictive value, and negative predictive value of frozen-section analysis were 28.5%, 100%, 100%, and 73.6%, respectively, according to the Feldman criterion and 71.4%, 64.2%, 50%, and 81.8%, respectively, according to the Athanasou criterion. The numbers of lymphocytes and plasma cells did not help in the diagnosis of infection. Fibrosis was more common in patients without an infection.
The probability of infection is high when at least five neutrophils per high-power field are found in the periprosthetic tissue, but it is not possible to rule out infection when the number of neutrophils is less than five.
Diagnostic Level I.
The Journal of Bone and Joint Surgery 07/2007; 89(6):1232-7. · 3.27 Impact Factor
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Clinical Orthopaedics and Related Research 11/2004; · 2.53 Impact Factor
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Medicina Clínica 11/2004; 123(13):509-15. · 1.38 Impact Factor
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ABSTRACT: To describe the chromosomal numerical changes present in primary prostate tumours and their matched lymph-node metastases, to identify a clonal cell migration process which could account for the metastatic behaviour.
Twenty-eight cases of unsuspected stage D1 (pT2-3pN1M0) prostate cancer were detected among patients who had a radical prostatectomy for clinically localized prostate cancer. Fluorescence in situ hybridization (FISH), using centromeric probes to enumerate chromosomes 7, 8, 10 and 12, was used to assess numerical chromosomal changes. FISH analysis was used on isolated nuclei obtained from matched primary tumours and their lymph node metastases.
Of the 28 suitable cases it was possible to complete the study in 18 pairs of matched tissues; the remainder were excluded because of insufficient tissue or poor preservation of at least one of the tissues. There was cytogenetic change (aneuploidy) in 16 of the 18 primary tumours, the most common being monosomy 8, detected in 14, followed by trisomy 7, in 13 aneuploid tumours. All lymph node metastases were aneuploid by FISH. As in the primary tumours, monosomy 8 and trisomy 7 were the most common cytogenetic alterations, in 13 and 15 of the lymph node tissues. FISH analysis showed a high correlation (83%) in the cytogenetic pattern of changes between the primary tumours and their lymph node metastases. Moreover, a similar number of cells had the most common aneusomies when comparing prostate and the lymph node tissues.
These results show a similar pattern of cytogenetic alteration in the primary tumour and its lymph node metastasis, characterized by the frequent presence of trisomy 7 and monosomy 8, suggesting that clonal cell selection is not involved in the metastatic process.
BJU International 09/2004; 94(3):407-11. · 2.84 Impact Factor
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ABSTRACT: OBJECTIVE
To describe the chromosomal numerical changes present in primary prostate tumours and their matched lymph-node metastases, to identify a clonal cell migration process which could account for the metastatic behaviour.MATERIALS AND METHODS
Twenty-eight cases of unsuspected stage D1 (pT2–3pN1M0) prostate cancer were detected among patients who had a radical prostatectomy for clinically localized prostate cancer. Fluorescence in situ hybridization (FISH), using centromeric probes to enumerate chromosomes 7, 8, 10 and 12, was used to assess numerical chromosomal changes. FISH analysis was used on isolated nuclei obtained from matched primary tumours and their lymph node metastases.RESULTSOf the 28 suitable cases it was possible to complete the study in 18 pairs of matched tissues; the remainder were excluded because of insufficient tissue or poor preservation of at least one of the tissues. There was cytogenetic change (aneuploidy) in 16 of the 18 primary tumours, the most common being monosomy 8, detected in 14, followed by trisomy 7, in 13 aneuploid tumours. All lymph node metastases were aneuploid by FISH. As in the primary tumours, monosomy 8 and trisomy 7 were the most common cytogenetic alterations, in 13 and 15 of the lymph node tissues. FISH analysis showed a high correlation (83%) in the cytogenetic pattern of changes between the primary tumours and their lymph node metastases. Moreover, a similar number of cells had the most common aneusomies when comparing prostate and the lymph node tissues.CONCLUSIONS
These results show a similar pattern of cytogenetic alteration in the primary tumour and its lymph node metastasis, characterized by the frequent presence of trisomy 7 and monosomy 8, suggesting that clonal cell selection is not involved in the metastatic process.
BJU International 08/2004; 94(3):407 - 411. · 2.84 Impact Factor
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ABSTRACT: Sarcomatoid (S) renal cell carcinoma (RCC) is an uncommon subtype of RCC with a poor prognosis because of its local aggressiveness and high metastatic rate. Currently, there is no specific, effective treatment for it. A relatively nontoxic tyrosine kinase inhibitor, imatinib (STI-571) has been approved as a target therapy in neoplasms that express c-Kit. We investigated c-Kit expression in this type of tumor, which to our knowledge has not been previously described.
We reviewed 215 cases of RCC diagnosed at our department from 1995 to 2002. Of the cases 20 (9.3%) were SRCC. Formalin fixed, paraffin embedded material was available in 19 cases. We performed immunohistochemical staining against c-Kit using rabbit polyclonal antihuman antibody (CD117, Dako Corp., Carpinteria, California), diluted 1:100. Its expression was evaluated in the epithelial and the spindle components.
Two of the 20 SRCC cases (10%) showed no epithelial differentiation. The epithelial component was conventional RCC in 10 cases (50%), papillary RCC in 5 (25%) and chromophobe RCC in 3 (15%). A total of 16 cases (80%) presented at an advanced stage at diagnosis, namely T3 or T4 and/or metastatic disease. Immunohistochemical study showed positivity in the epithelial component only in the 3 chromophobe SRCCs. The sarcomatoid component was positive for c-Kit in 18 cases (94.7%).
High c-Kit expression in SRCC in our series and the existence of a target therapy, imatinib (STI-571), against cells that express this receptor open the possibility of using this treatment for these tumors, especially in cases of advanced disease.
The Journal of Urology 07/2004; 171(6 Pt 1):2176-80. · 3.75 Impact Factor
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ABSTRACT: The overexpression of c-Kit in chromophobe renal cell carcinoma (ChRCC) has been described by comparative gene expression analyses and has been proposed as a possible specific hallmark of this neoplasm. The aim of our study was to establish its immunohistochemical expression in a large series of ChRCC and to compare it with other renal neoplasms. In our study, immunohistochemical characterization of KIT was performed in 87 renal neoplasms including 25 cases of ChRCC, 13 cases of renal oncocytoma, and 39 renal cell carcinomas (21 cases of conventional RCC [CRCC], 8 cases of CRCC with granular cell differentiation, and 10 cases of papillary RCC [PRCC]). Eighty-eight percent ChRCC and 71% oncocytomas showed immunohistochemical expression of KIT, while the other types of RCC studied were all negative. The meaning of immunohistochemical expression of KIT in ChRCC and oncocytomas is still unknown, but its immunohistochemical staining appears to be useful in distinguishing ChRCC from PRCC, CRCC, and its granular cell variant. Moreover, our findings support current models that consider that there is a histopathogenic relationship between oncocytoma and ChRCC. Finally, it should be determined whether KIT plays a role in the tumorigenesis of ChRCC and oncocytoma and whether targeted therapy with STI-571, an inhibitor of KIT, could be effective in exceptional cases of ChRCC with metastatic extension or recurrence.
American Journal of Surgical Pathology 06/2004; 28(5):676-8. · 4.35 Impact Factor
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Medicina Clínica 07/2003; 121(3):109-16. · 1.38 Impact Factor
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ABSTRACT: Urothelial dysplasia and carcinoma in situ (CIS) are related to recurrence and progression of urothelial carcinoma. Distinguishing CIS and dysplasia from reactive atypia is often difficult on the basis of histological features alone. Cytokeratin 20 (CK20), p53, and Ki-67 are related either to neoplastic change or prognosis in urothelial proliferations. The objective of the present study was to establish the immunohistochemical pattern of these three antibodies in urothelial dysplasia and CIS. Three groups of patients were evaluated: 40 nonneoplastic urothelial samples, 50 cases with histologically incontrovertible CIS, and 30 samples with nonconclusive atypical changes (atypia of unknown significance). Monoclonal antibodies (MoAb) against CK20, p53, and Ki-67 (MIB-1) were used on paraffin-embedded samples. Nonneoplastic urothelium showed no reactivity to CK20 except for umbrella cells; p53 and Ki-67 were negative or weakly positive in <10% of basal cells. In the CIS group, 42% showed positivity for all three MoAb; 44%, for two; and 14%, only for one. CK20 was positive through the full thickness of the urothelium in 72% of cases, p53 was positive in 80% of cases, and Ki-67, in 94% of cases. In the third group, the suspected dysplastic cells showed strong positivity in scattered cells through the epithelium in 75% of cases. Aberrant CK20 expression in urothelial cells plus overexpression of p53 and Ki-67 are indicators of dysplastic change in urothelial mucosa. Thus, immunohistochemistry is a useful tool to confirm the diagnosis of CIS and could be helpful to distinguish dysplastic changes from reactive atypia.
Modern Pathology 03/2003; 16(3):187-91. · 4.79 Impact Factor
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ABSTRACT: A rare case of low-grade primary leiomyosarcoma of the sacrum is described in a young woman who suffered from pain in the right sacroiliac region. A lytic sacral mass was observed on conventional radiology and CT studies. Magnetic resonance imaging clearly showed Gd-DTPA enhancement in the entire mass demonstrating its hypervascularity, which was later confirmed by angiography. Histopathology and immunohistochemical results of biopsy and curettage of the lesion confirmed the diagnosis. We report on the features of a rare tumor entity through imaging and diagnostic methods.
European Radiology 01/2003; 12 Suppl 3:S35-9. · 3.22 Impact Factor
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Medicina Clínica 06/2002; 118(16):627-33. · 1.38 Impact Factor
