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Biomedical subjects

Guido Bellezza

Publications and source records attributed to Guido Bellezza.

14 recordsLinked to original sources

A unique simultaneous occurrence of paratracheal granular cell tumor and papillary thyroid carcinoma.

We report an unusual case of granular cell tumor in the paratracheal region detected during total thyroidectomy for papillary carcinoma and clinically misdiagnosed as tracheal infiltration of thyroid neoplasia. Histologically, the granular cell tumor had infiltrated the thyroid gland close behind the papillary carcinoma. At immunohistochemical investigation, the cells showed diffuse positivity for S-100, neuron-specific enolase, and CD68, and surprisingly, positivity also for galectin-3 and HBME-1. A granular cell tumor should also be considered in the cytologic differential diagnosis of the thyroid and paratracheal nodules.

Biomarkers, Tumor↗

Ductal carcinoma in situ with microinvasion: clinicopathologic study and biopathologic profile.

Data regarding the biologic behavior and surgical management, in particular the axillary lymph node excision, of ductal carcinoma in situ with microinvasion (DCIS-MI) are controversial. Therefore, we decided to study the histopathologic characteristics, the biopathologic profile, as well as the follow-up of a group of patients with DCIS-MI. Thirty-one cases of DCIS-MI, 21 of whom were treated with axillary lymph node dissection, were studied. All cases were classified according to the Van Nuys classification, and the extension of DCIS was quantified. The biopathologic profile (ER, PR, MIB 1, p53, c-erbB-2) as well as the follow-up was also investigated. The results did not reveal any statistically significant differences between the two groups, and there was no statistically significant relationship between the extension of DCIS and the number of microinvasion (MI) foci or maximum MI diameter, or between Van Nuys classification of DCIS and again the number of MI foci or maximum MI diameter. DCIS-MI seems associated with good prognosis. None of the patients had relapses or metastases. Our data seem to suggest that the natural history of DCIS-MI resembles DCIS, and we, therefore, suggest that all the surgically removed area should be examined histologically to avoid missing foci of infiltrating breast cancer larger than 1mm.

Adult↗

Biopathologic profile of breast cancer core biopsy: is it always a valid method?

For breast cancer management biopathologic profile and particularly the expression of estrogen receptor (ER) and progesterone receptor (PR) is considered essential. In advanced cases, core biopsy results are the only data available. To evaluate reliability of data, results of ER, PR, MIB1, p53 and c-erbB2 on core biopsy were compared with those on surgical specimens. Results showed a statistically significant concordance for ER and PR in pT1 but not in pT2 tumors, possibly due to breast cancer heterogeneity. MIB1 results were worse with no significant concordance even for pT1 group. There was statistically significant concordance in pT1 and pT2 groups for p53 and c-erbB 2, probably due to the high number of negative cases for these markers. We recommend more core biopsies for larger tumors since core biopsy has a high probability for giving unreliable data in these cases. In conclusion, this study showed that core biopsy has a high probability for not very reliable data in bigger tumors where the results obtained might be the only data available. A higher number of core biopsy is recommended in those cases.

Adult↗

Ectopic prostatic tissue in the bladder.

Ectopic prostatic tissue in the bladder has rarely been reported and usually involves the midline in the form of vestigial remains of embryonic prostatic elements. To our knowledge there are only 32 reports on this lesion in the literature in English. Prostatic heterotopia may be endoscopically confused with malignancy in the urinary system. We report three cases of ectopic prostatic tissue at the retrotrigonal area and left ureteral orifice. The patients presented with gross or microscopic hematuria and all the lesions had a polypoid appearance. The histopathologic and immunohistochemical examination revealed the prostatic nature of the tissue. No recurrences were evidenced. The authors review the literature concerning this lesion which should be recognized by urologists and pathologists, who must be aware of its benign nature.

Aged↗

Akt phosphorylation and gefitinib efficacy in patients with advanced non-small-cell lung cancer.

BACKGROUND: Gefitinib, a specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has activity against approximately 10% of unselected non-small-cell lung cancer (NSCLC) patients. Phosphatidylinositol 3'-kinase (PI3K)/Akt and Ras/Raf/mitogen-activated protein kinase (MAPK), the two main EGFR-signaling pathways, mediate EGFR effects on proliferation and survival. Because activation of these pathways is dependent on the phosphorylation status of the components, we evaluated the association between phosphorylation status of Akt (P-Akt) and MAPK (P-MAPK) and gefitinib activity in patients with advanced NSCLC. METHODS: Consecutive patients (n = 106) with NSCLC who had progressed or relapsed on standard therapy received gefitinib (250 mg/day) until disease progression, unacceptable toxicity, or patient refusal. P-Akt and P-MAPK positivity was determined with immunohistochemistry using tumor tissues obtained before any anticancer treatment. Association of P-Akt and time to progression was determined by univariable and multivariable analyses. All statistical tests were two-sided. RESULTS: Of the 103 evaluable patients, 51 (49.5%) had tumors that were positive for P-Akt, and 23 (22.3%) had tumors that were positive for P-MAPK. P-Akt-positivity status was statistically significantly associated with being female (P<.001), with never-smoking history (P =.004), and with bronchioloalveolar carcinoma histology (P =.034). Compared with patients whose tumors were negative for P-Akt, patients whose tumors were positive for P-Akt had a better response rate (26.1% versus 3.9%; P =.003), disease control rate (60.9% versus 23.5%; P<.001), and time to progression (5.5 versus 2.8 months; P =.004). Response rate, disease control rate, and time to progression did not differ according to P-MAPK status. The multivariable analysis showed that P-Akt positivity was associated with a reduced risk of disease progression (hazard ratio = 0.58, 95% confidence interval = 0.35 to 0.94). CONCLUSIONS: Patients with P-Akt-positive tumors who received gefitinib had a better response rate, disease control rate, and time to progression than patients with P-Akt-negative tumors, suggesting that gefitinib may be most effective in patients with basal Akt activation.

Adult↗

Biopathological profile of multiple synchronous homolateral and bilateral breast cancers.

It still needs to be verified whether multiple syncronous homolateral and bilateral breast cancers represent intramammary spread of a single tumor or two or more separate neoplastic events. To clarify this problem, we studied the biopathological profile of 46 homolateral and 20 bilateral cases. The cancers were always surgically removed and processed at the same time. The expression of estrogen receptors (ER), progesterone receptors (PR), MIB 1, p53, and c-erbB-2 was determined. Computer-assisted image analysis (CAS 200) was used to evaluate ER, PR, MIB 1, and p53. The histological concordance was 95.6% in homolateral and 50% in bilateral cases. The immunophenotype profile of multiple homolateral neoplasms showed a concordance between 93.47% for ER and 78.26% for p53. The results were statistically significant for all parameters except for p53. In bilateral cancers, there was a significant statistical concordance for ER. These data strongly suggest that both mechanisms may exert an influence and, in particular, that in the majority of homolateral carcinomas, there may be intramammary spread of tumor cells. In multiple bilateral tumors, however, the great diversity of the histological aspects and the differences in the immunophenotype pattern suggest that the vast majority of these may constitute independent multiple events.

Adult↗

Primary cutaneous leiomyosarcoma: a clinicopathological and immunohistochemical study of 7 cases.

Primary cutaneous leiomyosarcomas are rare tumors, few series being reported in the current literature. A retrospective study of 7 cases was undertaken to understand the clinicopathological characteristics of these neoplasms and some of their molecular mutations. Histologically, a well-differentiated proliferation of cells of smooth muscle derivation was evident in all cases. The number of mitoses was considered the most important criterion of malignancy (more than 2 for 10 HPF). Smooth muscle actin, desmin, and vimentin were positive in all cases. Immunohistochemical analysis also revealed a positivity for p53 in 3 cases and no reaction for retinoblastoma protein. Research for Epstein-Barr virus was negative in all cases. Three patients developed local recurrences owing to incomplete surgical excision. Recurrent tumors were more atypical and located deeper. No distant metastases were observed. Our results emphasize that cutaneous leiomyosarcomas have an indolent biological course if treated by surgical excision with wide margins. Molecular abnormalities involving tumor suppressor genes are probably involved.

Aged↗

Pigmented "black" pheochromocytoma of the adrenal gland: a case report and review of the literature.

A pigmented "black" mass was discovered incidentally in a 72-year-old woman. The tumor, which was detected near the upper pole of the left kidney, was cystic and intensely black throughout with the presence of abundant, coarse, dark brown to black pigment granules. Histologic examination showed a proliferation of monomorphous neoplastic cells arranged in a typical zellballen growth pattern. These features indicated a diagnosis of pheochromocytoma. Immunostains for chromogranin A, synaptophysin, and neuron-specific enolase were positive. The immunostain for HMB-45 was negative. Electron microscopy showed neurosecretory-type granules and larger pleomorphic granules, which were considered most consistent with neuromelanin, a waste product of catecholamine metabolism. The evidence of melanin or melanin-like pigment in the adrenal gland has been described in only 10 cases in the literature and is always a microscopic finding. The case reported here is unique for the characteristic black macroscopic appearance and the abundance of pigment.

Adrenal Gland Neoplasms↗

The clinical relevance of Bcl-2, Rb and p53 expression in advanced non-small cell lung cancer.

PURPOSE: The aim of this study was to evaluate the impact of Bcl-2, retinoblastoma (Rb) and p53 proteins on overall survival of 102 patients with locally advanced and metastatic NSCLC who underwent cisplatin-based chemotherapy. MATERIALS AND METHODS: Paraffin-embedded bronchial biopsy and fine-needle biopsy specimens were evaluated by an immunostaining method. RESULTS: Median age of analyzed patients was 61 years. Male/female ratio was 88/14. There were 10 (10%) patients with stage IIIA, 37 (36%) with stage IIIB and 55 (54%) with stage IV NSCLC. Only 15 (15%) tumor specimens had no detectable alterations for analyzed factors. Forty-six samples (45%) had positive immunostaining for p53, 61 (60%) had negative immunostaining for Rb and 8 (8%) had positive immunostaining for Bcl-2. Median and 5-year survival of analyzed population was 12 months and 6%, respectively. In univariate analysis Bcl-2 overexpression, stage (III versus IV) and normal lactate dehydrogenase (LDH) serum levels were associated with better overall survival (P<0.02, 0.001 and 0.03). In multivariate analysis, only stage was identified as an independent predictive factor. CONCLUSION: High frequency of Rb and Bcl-2 loss was detected in patients with advanced NSCLC. P53, Rb and Bcl-2 have not been shown to be independent predictors of survival even if Bcl-2 might have a particular relevance in patients with advanced NSCLC and should be better explored in this setting.

Adult↗

Relevance of p53, bcl-2 and Rb expression on resistance to cisplatin-based chemotherapy in advanced non-small cell lung cancer.

PURPOSE: Tumors with p53 overexpression have been associated with enhanced resistance to cisplatin-based chemotherapy in a few and small studies involving non-small cell lung cancer. The relationships and interactions between p53, Rb and bcl-2 immunostaining, clinical parameters and response to cisplatin-based chemotherapy were evaluated in the present study. EXPERIMENTAL DESIGN: Histological specimens obtained by bronchial or fine-needle biopsy from patients who underwent cisplatin-based chemotherapy between 1992 and 1999 were evaluated by immunostaining. RESULTS: There were 102 patients, 88 men. Median age was 63 years; 47 had stage III and 55 stage IV disease. Forty-six tumor samples (45%) had positive immunostaining for p53, 61 (59%) had negative immunostaining for Rb and 8 (8%) had positive immunostaining for bcl-2. The response rate of the group with p53 positive immunostaining was 26% versus 57% of the p53 negative group (P=0.004). In multivariate analyses p53 positive immunostaining was identified as an independent predictive factor for resistance to cisplatin-based chemotherapy (P=0.006). CONCLUSIONS: Our study confirmed an association of p53 immunostaining and response rate of patients treated with cisplatin-based chemotherapy.

Carcinoma, Non-Small-Cell Lung↗

The correlation of protein peroxidation with morphological changes in experimental oestradiol-induced carcinogenesis.

Oestradiol-induced male Syrian hamster carcinogenesis is a well-known experimental model of human cancer of the breast, ovary and uterus. The pathomechanism postulated in this model is 4-hydroxylation of oestradiol and further free radical formation. The same process is suspected in human breast cancer. Dynamic changes in protein peroxidation were reported during the tumour induction. In this paper we try to correlate the protein peroxidation markers with the histopathological progression of the changes. The biochemical and histopathological evaluations were performed after 1, 3, 6 and 9 months of the hormone exposition. Significant protein peroxidation was observed as soon as after 1 month and increased further until the 6th month. After 9 months however, it was not significantly different from the control. The discrete histopathological changes after 1 month, progressed into tubular and interstitial hyperplasias after 3 and 6 months. After 9 months several dysplastic areas, sometimes with features of carcinoma in situ, were observed. The severe 9-month histopathological changes did not correlate with the protein peroxidation.

Animals↗

Coexpression of HER-2/neu and p53 in breast cancer identifies a subset with an aggressive biopathological profile.

AIMS AND BACKGROUND: Amplification/overexpression of HER-2/neu and inactivation of p53 may be reliable parameters for the prognostic assessment of breast carcinomas. Several studies have addressed the prognostic significance of simultaneous expression of these gene abnormalities with controversial results. METHODS: In this study we analyzed the biopathological profile of 45 breast cancers with both HER-2/neu and p53 overexpression and compared their features with those of 45 randomly selected cases negative for these gene products. RESULTS: Tumors with HER-2/neu and p53 coexpression were found in younger patients, were more often multifocal and/or multicentric, were poorly differentiated in 55% of cases and lymph node-positive in 57%, showing a statistically significant difference compared to tumors with neither alteration (11% and 28%, respectively). Moreover, they were prevalently negative for estrogen (71% vs 22%) and progesterone receptors (78% vs 40%) and showed a higher proliferative activity. CONCLUSIONS: Our data demonstrate that the coexpression of p53 and HER-2/neu is an additive effect in terms of genetic instability reflected by both morphological and biological adverse features; patients with such coexpression should be assigned to specific therapeutic and follow-up protocols.

Aged↗

Detection of HER-2/neu (c-erbB-2) overexpression and amplification in breast carcinomas with ambiguous immunohistochemical results. A further contribution to defining the role of fluorescent in situ hybridization.

BACKGROUND: The assessment of HER-2/neu status is a prerequisite in the clinical management of patients with breast cancer in order to obtain prognostic and predictive information, including Herceptin sensitivity. Immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) are the techniques recommended to detect HER-2/neu alterations and considerable attention is currently being focused on the standardization of these techniques. Intrinsic limitations of IHC, such as antigen preservation and antibody specificity, may make it difficult to score the membrane staining thereby resulting in inconclusive results. PATIENTS AND METHODS: In this study, 65 invasive breast carcinomas, with doubtful IHC results using the monoclonal antibody CB11, were reanalyzed with two recently licensed assays, the Hercep Test (IHC) and the Path Vision (FISH). RESULTS: IHC with Hercep Test detected HER-2 protein overexpression in 72% of cases, including nine (14%) strongly positive (3+), 13 (20%) medium positive (2+) and 25 (38%) weakly positive (1+) specimens. FISH testing, with interpretable results in 48 cases, showed a moderate HER-2 gene amplification in only 22% of carcinomas with 2+ or 3+ overexpression. CONCLUSION: These data indicated an excessive sensitivity of the Hercep Test and suggested that, in the case of indeterminate results after standard IHC, the FISH technique is the best approach to establish HER-2 status.

Adult↗

Inflammatory myofibroblastic tumor of the larynx with anaplastic lymphoma kinase (ALK) protein overexpression. A case report.

Inflammatory myofibroblastic tumor is an uncommon lesion which mainly develops in the lung and is extremely rare in the larynx. It may be easily misinterpreted as a malignant epithelial or mesenchymal spindle cell neoplasm. Histological and clinical knowledge of this lesion is important to exclude misdiagnosis and inappropriate treatment. We report a case of inflammatory myofibroblastic tumor arising on the right vocal cord of a 23-year-old man. The tumor was composed of a mixture of spindle cells and inflammatory elements. Immunohistochemical investigation revealed that the neoplastic cells expressed anaplastic lymphoma kinase (ALK) protein.

Adult↗