Analysis of the CAVEOLIN-1 gene at human chromosome 7q31.1 in primary tumours and tumour-derived cell lines.
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We identified CAVEOLIN-1 as a candidate for a tumour suppressor gene mapping to human chromosome 7q31.1. A number of studies suggest that caveolin could function as a tumour suppressor. Expression of caveolin, and in turn the number of caveolae within a cell, are inversely correlated with the transforming ability of numerous oncoproteins, including H-ras, v-abl, and bcr-abl, and caveolin is a major transformation-dependent substrate of v-src. Heterologous expression of caveolin has been shown to abrogate anchorage-independent growth and induce apoptosis in transformed fibroblasts and also to suppress anchorage-independent growth in human mammary carcinoma cells. We have analysed the status and expression of the human CAVEOLIN-1 gene in primary tumours and tumour-derived cell lines. We found no evidence for mutation of CAVEOLIN-1 in human cancers. Additionally, we found that while the first two exons of CAVEOLIN-1 are associated with a CpG island, this is not methylated in either primary tumours or in tumour-derived cell lines in which Caveolin-1 expression is low or undetectable. The level of expression of Caveolin-1 does not correlate with loss of heterozygosity at the CAVEOLIN-1 locus in these same cell lines. Contrary to other published studies, we have shown that CAVEOLIN-1 is not expressed in normal breast ductal epithelial cells in vivo. CAVEOLIN-1 is however highly expressed in breast myoepithelial cells and its expression is retained in tumours derived from breast myoepithelium. Together our data refute a role for CAVEOLIN-1 as a breast tumour suppressor gene in vivo. (+info)
The mammary myoepithelial cell--Cinderella or ugly sister?
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The breast myoepithelial cell is the Cinderella of mammary biology. Although its contribution to benign and some malignant pathologies is recognised, it has been largely neglected in molecular and biological studies. The reason for this has been the perception that its role in normal physiology is confined to lactation and the belief that most breast cancers arise from luminal epithelial cells. This review presents our perspective on its broader biological significance and its potential use as a model system for understanding breast carcinogenesis. (+info)
Pulmonary epithelial-myoepithelial tumor of unproven malignant potential: report of a case and review of the literature.
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Epithelial-myoepithelial tumors of the lung are rare neoplasms whose biological behavior and clinical course still remain to be defined. A case of epithelial-myoepithelial tumor of the lung arising from bronchial mucosa-submucosa and occurring as a polypoid lesion of the upper left bronchus in a 47-year-old man is reported. The tumor did not infiltrate the cartilaginous wall of the bronchus and showed a biphasic histological appearance with a double layering of epithelial and myoepithelial cells. Myoepithelial spindle cells with eosinophilic cytoplasm were also observed. Mitotic figures were very rare and necrosis absent. Immunohistochemical study for epithelial and muscular markers confirmed the presence of a double-cell component in the tumor, namely epithelial and myoepithelial. The patient is alive and well, with no evidence of recurrent or metastatic disease 6 months after surgery. On the basis of the present case and the six previously reported cases, we suggest using the noncommittal term pulmonary epithelial-myoepithelial tumor of unproven malignant potential (PEMTUMP) for this type of neoplasm. In addition, we first introduce p63 as a novel marker for highlighting the myoepithelial cells of the respiratory tract and speculate on the role of these cells in the development of this unusual tumor. (+info)
CGH analysis of ductal carcinoma of the breast with basaloid/myoepithelial cell differentiation.
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2-18% of ductal carcinoma-No Special Type (NST) are reported to express basal cell keratin 14 and such tumours may have a different metastatic pattern and prognosis. We performed immunohistochemistry for cytokeratins 19 (luminal) and 14 (basal) on 92 ductal carcinoma-NST. Those tumours showing CK14 expression were further characterized by immunohistochemistry for myoepithelial cell phenotype and analysed by comparative genomic hybridization. The 7 cases of ductal carcinoma-NST exhibiting a basal cell phenotype were all grade III tumours and showed a molecular cytogenetic profile similar to more conventional myoepithelial cell carcinomas. Therefore it appears that grade III invasive ductal carcinomas contain a subset of tumours with specific morphological and cytogenetic characteristics, and probably prognosis for the patient. (+info)
Radiologic-pathologic correlation of unusual lingual masses: Part II: benign and malignant tumors.
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Because the tongue is superficially located and the initial manifestation of most diseases occurring there is mucosal change, lingual lesions can be easily accessed and diagnosed without imaging analysis. Some lingual neoplasms, however, may manifest as a submucosal bulge and be located in a deep portion of the tongue, such as its base; their true characteristics and extent may be recognized only on cross-sectional images such as those obtained by CT or MRI. Some uncommon tongue neoplasms may have characteristic radiologic features, thus permitting quite specific radiologic diagnosis. Lipomas typically manifest at both CT and MR imaging as homogeneous nonenhancing lesions. Relative to subcutaneous fat they are isoattenuating on CT images, and all MR sequences show them as isointense. Due to the paramagnetic properties of melanin, metastases from melanotic melanoma usually demonstrate high signal intensity on T1-weighted MR images and low signal intensity on T2-weighted images. Although the radiologic findings for other submucosal neoplasms are nonspecific, CT and MR imaging can play an important role in the diagnostic work-up of these unusual tumors. Delineation of the extent of the tumor, and recognition and understanding of the spectrum of imaging and the pathologic features of these lesions, often help narrow the differential diagnosis. (+info)
Cytology of myoepithelial carcinoma of the salivary gland.
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BACKGROUND: Myoepithelial carcinoma, also know as malignant myoepithelioma, is rare in the salivary gland, and its cytologic features have rarely been reported. DESIGN: Four cases of myoepithelial carcinoma with cytology were retrieved from the archives of the Pathology Departments of two academic institutes. In three cases, the specimens were obtained by fine needle aspiration biopsy (FNA); the remaining case was a bench aspiration performed on the surgically resected specimen at the time of intra-operative consultation. The cytologic features were reviewed and correlated with the histology. RESULTS: The four patients with myoepithelial carcinoma (two men and two women) ranged in age from 48 to 64 years. Three cases arose from the parotid gland, and the remaining case was a recurrent tumor in the minor salivary glands of the hard palate. The aspirates of two cases consisted of predominantly spindle cells, one predominantly epithelioid/plasmacytoid cells, and one with a mixture of both spindle and epithelioid/plasmacytoid cells. Cellular pleomorphism was noted in two cases and mitotic figures in three cases. Two cases were cytologically diagnosed as malignant spindle cell neoplasm, not otherwise specified. The FNA of the recurrent tumor was diagnosed as consistent with the previous malignancy. The remaining case was interpreted as a pleomorphic adenoma with atypia. CONCLUSIONS: The cytologic features of myoepithelial carcinoma are diverse and may lack overt features of malignancy. Pathologists should be aware of this entity when evaluating cytologic specimen of salivary gland mass. (+info)
A case of myoepithelial carcinoma displaying biallelic inactivation of the tumour suppressor gene APC in a patient with familial adenomatous polyposis.
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Familial adenomatous polyposis (FAP) is an autosomal dominant disorder caused by mutation of the APC gene. It is characterised by the appearance of hundreds to thousands of colorectal adenomas in adolescence and the subsequent development of colorectal cancer. Various extracolonic malignancies are associated with FAP, including desmoids and neoplasms of the stomach, duodenum, pancreas, liver, and brain. We present a family affected by FAP with an exon 14 APC mutation displaying two rare extracolonic lesions, a hepatoblastoma and a myoepithelial carcinoma. The hepatoblastoma was found in a male patient aged 2 years. The second lesion, a myoepithelial carcinoma of the right cheek, was found in a female patient aged 14 years. Inactivation of the normal APC allele was demonstrated in this lesion by loss of heterozygosity analysis, thus implicating APC in the initiation or progression of this neoplasm. This is the first reported case of this lesion in a family affected by FAP. (+info)
Myoepithelial carcinoma of the salivary glands: behavior and management.
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OBJECTIVE: To investigate the biological behavior and proper management of myoepithelial carcinomas of salivary glands. METHODS: Twenty-seven cases of myoepithelial carcinoma of salivary glands were retrospectively studied and their detailed clinical and follow-up data were presented. RESULTS: The subjects consisted of 17 men and 10 women aged 16 to 73 years (mean age: 51 years). The parotid gland was the most common site (n = 14) of cancer. Clinical features included extensive local growth, invasion of the surrounding tissues, infrequent cervical lymph node metastasis but high rates of distant metastasis, frequent/multiple recurrences and poor prognosis. CONCLUSIONS: Myoepithelial carcinomas of the salivary gland should be classified as high-grade malignancies. Early and radical surgery with close follow-up are essential for achieving favorable outcomes. Radiotherapy appears to be non-sensitive and elective neck dissection is generally unnecessary. (+info)