Variable phenotype associated with SP-C gene mutations: fatal case with the I73T mutation.
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Biomedical subjects
Publications and source records attributed to G Pettinato.
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The HOX network contains 39 genes that act as transcriptional regulators and control crucial cellular functions during both embryonic development and adult life. Inside the network, this is achieved according to the rules of temporal and spatial co-linearity with 3' HOX genes acting on the anterior part of the body, central HOX genes on the thoracic part and lumbo-sacral HOX genes on the caudal region. We analysed HOX gene expression in normal breast tissue and in primary breast cancers by reverse-transcriptase-polymerase chain reaction (RT-PCR). 17 out of 39 HOX genes were expressed in the normal breast tissue. The expression of thoracic HOX genes tended to be similar in normal and neoplastic breast tissues suggesting that these genes are involved in breast organogenesis. In contrast, cervical and lumbo-sacral HOX gene expression was altered in the primary breast cancers with respect to normal breast tissue. This supports their involvement in breast cancer evolution and suggests they could be targets for future cancer therapies.
AIMS: Hashimoto's thyroiditis (HT) is an autoimmune disease in which both proliferation and apoptosis are enhanced. p27(Kip1) protein protects tissues from disease mechanisms that involve excessive cell proliferation and apoptosis. This study investigated whether there is loss of p27(Kip1) expression in HT and whether p27(Kip1) immunoreactivity has any relation to the proliferative indicator Ki-67. Because p27(Kip1) is regulated through either degradation, mediated by the S phase kinase associated protein 2 (Skp2), or sequestration, via D3 cyclin, the expression of these proteins was also investigated. METHODS: Immunohistochemistry was used to assess p27(Kip1), Ki-67, Skp2, and cyclin D3 expression in 19 cases of HT and in 10 normal thyroids. The results were evaluated by image analysis and reported as labelling indices (LIs) in both groups. RESULTS: The p27(Kip1) LI was lower in HT than in normal thyroid (28% v 75%; p < 0.001), whereas Ki-67 (1.13% v 0.13%), Skp2 (0.74% v 0.15%), and cyclin D3 (1.56% v 0.00%) LIs were higher in HT than in normal thyroids (p < 0.001). There was no correlation between p27(Kip1) and the expression of Ki-67, Skp2, and cyclin D3. CONCLUSIONS: p27(Kip1) downregulation is not exclusive to tumours but occurs also in HT, independently of the proliferative status and of changes in Skp2 and cyclin D3 expression. Further investigation is required to understand the mechanisms leading to p27 deregulation because these observations suggest that the regulation of p27(Kip1) expression in epithelial thyroid cells may play a role in HT pathogenesis.
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PURPOSE: To evaluate the predictive value of sentinel lymph node biopsy versus axillary node dissection on lymph node status in patients with T1-T2 breast cancer. MATERIAL AND METHODS: Twenty-nine patients with T1 and 12 with T2 breast carcinoma and clinically N0 axillary lymph nodes, underwent lymphoscintigraphy following the administration of 99mTc-human albumin nanocolloids. The tracer was injected subdermally, over the tumor mass, in the 34 patients with palpable lesions and peritumorally (n=3) or intratumorally (n=4), under stereotactic or ultrasound guidance, in the 7 patients with non-palpable lesions. Anterior and lateral planar images were acquired 15 min after the injection of the tracer and repeated every 30 min up to 3 hr until identification of sentinel lymph node. At the end of the scintigraphic study, sentinel node skin projection was marked using a dermographic pen. Eighteen hours after lymphoscintigraphy, sentinel lymph node was identified and removed during surgery by hand-held gamma probe, then, the remaining axillary lymph nodes were dissected. All surgical specimens underwent histologic examination. Sentinel lymph nodes free of metastasis at histology, underwent additional examination with immunohistochemistry using monoclonal antibodies against cytokeratin and EMA to search for micrometastases. RESULTS: Sentinel lymph node was identified in the 34 patients injected subdermally and in the 3 patients injected peritumorally, while it remained undetected in the 4 patients injected intratumorally except for one case in which it was isolated by radioguided surgery but not scintigraphically. Sentinel nodes resulted free of metastases both at histology and immunohistochemistry in 32 cases and metastatic in 6. In the 32 patients with non-metastatic sentinel lymph nodes the other axillary nodes were also free of metastases. Among the 6 metastatic sentinel lymph nodes, in 3 cases they were the only metastatic nodes of the axilla while in the other 3 cases metastases were spread to other axillary nodes. CONCLUSIONS: In agreement with previous studies, our results showed that sentinel lymph node radioguided biopsy is a simple and reliable method for predicting axillary lymph nodes status and for avoiding axillary dissection in early breast cancer patients with sentinel node free of metastases.
Testicular tumours represent 2% of all male malignancies, mostly concerning young men (20-40 years old). The polyembryoma is one of the uncommonest lesions and just recently it has been identified as autonomous nosographic entity. The reported case is peculiar because the patient was older than the most ones described in the literature and the tumour arose after polychemotherapy for non Hodgkins' disease. The Authors analyse some aspects concerning etiology, pathology and clinical approach to such rare neoplasm.
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A case of Kaposi sarcoma with HIV-negative and sequence of HHV-8 positive and exclusive rectosigmoid and descending colon involvement without immunodeficiency is reported. Histologically, in addition to typical features of Kaposi sarcoma, Cowdry type A inclusions were seen. PCR analysis of the tumor showed positivity for human herpesvirus 8. Two of the six reported cases of Kaposi sarcoma limited to the bowel were from African men before the AIDS epidemic. J. Surg. Oncol. 2001;76:197-200.
3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are established drugs for the treatment of hypercholesterolemia, but several studies have shown that benefits obtained with these drugs are not causally related only to regression of cholesterol lowering. Moreover, in experimental models of progressive renal disease, statins have reduced the extent of glomerulosclerosis. This study evaluated the antiproteinuric effect of a daily dose of 40 mg fluvastatin for 6 months in moderately proteinuric patients with immunoglobulin A nephropathy, stable renal function, and no indicators of poor long-term prognosis. The effects of therapy were evaluated on the basis of 24-hour proteinuria (total proteinuria and albuminuria), albuminemia, creatinine clearance, cholesterol, and triglyceride values. Renal function remained stable in all patients. A significant decrease in proteinuria was observed after 6 months of therapy and persisted for all the observations. An increase in serum albumin was observed after 6 months of therapy. This study suggests that there is an antiproteinuric effect of HMG-CoA reductase inhibitors in moderately proteinuric patients with immunoglobulin A nephropathy.
Amyloid deposition in secondary amyloidosis frequently involves thyroid gland, but rarely is responsible of a goiter. Amyloid goiter in secondary amyloidosis is characterized by deposition of amyloid A protein (AA) in the gland, associated to atrophic follicles. We identified cases of amyloid goiter in the files of our department in the period from 1985 to 1998. Five cases of amyloid goiter with ingravescent symptomatology, characterized by dyspnea, dysphagia and hoarseness were selected. In four cases of five we observed predisposing conditions as, for example, tuberculosis, Crohn's disease, or rheumatoid arthritis. In all cases the symptoms relative to thyroid enlargement preceded or, anyway, predominated over other clinical evidence of systemic amyloidosis. In one case a symptomatology of systemic amyloidosis was not evident. We would like to underline that in all cases the immunoreactivity for amyloid A in the amorphous material present in the gland permitted the diagnosis of secondary amyloidosis even in the absence of systemic symptoms.
We have established a cell line (TB) from a cerebrospinal fluid (CSF) specimen of a patient with a primary leptomeningeal melanomatosis. TB cell line was immunoreactive with the antibodies for low molecular weight neurofilament protein, vimentin, neuron-specific enolase, chromogranin, synaptophysin and HMB-45 (an antibody sensitive and specific for melanoma). When TB cells were transplanted into nude mice, the same immunohistochemical pattern present in cultured cells was found but surprisingly, a positive staining for desmin was observed. Significant amounts of serotonin and its metabolite were detectable. Retinoic acid but not nerve growth factor was able to induce differentiation towards a neuronal phenotype. In summary, TB cells represent primitive neuroectodermal cells having the potential for neuronal, myoblastic and possibly melanoblastic differentiation.
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We evaluated blood concentrations of bcl-2, a proto-oncogene that can inhibit apoptotic phenomena, in a group of patients with immunoglobulin A (IgA) nephropathy. Concentrations of bcl-2 were higher in patients with proteinuria than in those without proteinuria. A 6-month course of 5 mg/day lisinopril given to subjects with proteinuria significantly reduced blood bcl-2 concentrations and caused a reduction in proteinuria. Therefore increased blood bcl-2 concentrations may be considered an index of risk in subjects with IgA nephropathy, and the positive effects of angiotensin-converting enzyme inhibitors on proteinuria in patients with IgA nephropathy may be attributed, at least in part, to their effect on the mechanisms that regulate apoptosis. This is of fundamental importance in resolving glomerular hypercellularity in the course of glomerulonephritis.
Ten cases of breast hamartomas were reviewed; the patients' age ranged from 31 to 55 (mean 40.4, median 39). All cases presented with a palpable, sometimes tender, lump. The typical mammographic feature was a well defined, round to lens shaped, variable dense mass, occasionally surrounded by a thin radiolucent zone. All hamartomas were unilateral (4 in the right and 6 in the left breast, respectively) and no recurrence occurred after local excision. The tumor size ranged from 5 to 150 mm (mean 54 mm). Histologically all hamartomas were composed of a typical fibrous, adipose and glandular tissue combination. Immunohistochemically there was a strong positivity for cytokeratin and epithelial membrane antigen in the epithelial cells, a positive finding for vimentin and muscle-specific actin in stromal and myoepithelial cells, and for S-100 protein in myoepithelial cells. Vessels endothelial cells were immunoreactive for Factor VIII. Immunohistochemical analysis of hormone receptors completed on formaldehyde-fixed paraffin-embedded specimens, showed estrogen and progesterone receptors positivity in 9 cases and estrogen positive progesterone negative receptors in one case. In all cases the receptorial positivity was limited to the epithelial elements. These data revealed that 1) breast hamartoma is a benign, tumor-like lesion, histologically dissimilar from other lesions such as fibroadenoma and pseudoangiomatous hyperplasia; and 2) hamartoma tissue is influenced by hormones like the surrounding normal breast parenchyma.
This article describes histopathological, immunohistologic, and morphometric features of an epithelioid haemangioendothelioma that presented in the breast of a 30-year-old woman. Histologically the tumour was composed of large round, polygonal, slightly spindle shaped endothelial cells lying in a myxoid matrix. The lesion exhibited primitive vasoformation characterized by the presence of cytoplasmic vacuoles. The tumour cells reacted positively to F-VIII related antigen, whereas mammary ducts entrapped by the tumour cells reacted positively with keratin. Although the breast is an unusual location for this type of lesion, epithelioid haemangioendothelioma should be considered a rare differential diagnosis of a breast mass.
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