1/7. Characterization of human MMTV-like (HML) elements similar to a sequence that was highly expressed in a human breast cancer: further definition of the HML-6 group.Previously, we found a retroviral sequence, HML-6.2BC1, to be expressed at high levels in a multifocal ductal breast cancer from a 41-year-old woman who also developed ovarian carcinoma. The sequence of a human genomic clone (HML-6.28) selected by high-stringency hybridization with HML-6.2BC1 is reported here. It was 99% identical to HML-6.2BC1 and gave the same restriction fragments as total dna. HML-6.28 is a 4.7-kb provirus with a 5'LTR, truncated in RT. Data from two similar genomic clones and sequences found in GenBank are also reported. Overlaps between them gave a rather complete picture of the HML-6.2BC1-like human endogenous retroviral elements. work with somatic cell hybrids and FISH localized HML-6.28 to chromosome 6, band p21, close to the MHC region. The causal role of HML-6.28 in breast cancer remains unclear. Nevertheless, the ca. 20 Myr old HML-6 sequences enabled the definition of common and unique features of type A, B, and D (ABD) retroviruses. In Gag, HML-6 has no intervening sequences between matrix and capsid proteins, unlike extant exogenous ABD viruses, possibly an ancestral feature. Alignment of the dUTPase showed it to be present in all ABD viruses, but gave a phylogenetic tree different from trees made from other ABD genes, indicating a distinct phylogeny of dUTPase. A conserved 24-mer sequence in the amino terminus of some ABD envelope genes suggested a conserved function.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/7. Cushing's syndrome secondary to ectopic ACTH secretion from metastatic breast carcinoma.breast carcinoma is a rare cause of ectopic ACTH syndrome. There are only two previously reported cases in which ACTH secretion is documented. We describe the case of a 56-year-old woman who presented with clinical and biochemical features of ectopic ACTH syndrome in the setting of metastatic breast carcinoma. Despite aggressive management of her ectopic ACTH syndrome, her course was complicated by opportunistic infection, respiratory failure and death. Immunostaining of the breast metastases for ACTH was positive and in situ hybridization revealed proopiomelanocortin gene expression. This is the first reported case of ectopic ACTH syndrome associated with metastatic breast cancer in which the technique of in situ hybridization has been used to confirm the breast cancer metastases as the source of ectopic ACTH secretion.- - - - - - - - - - ranking = 2keywords = hybridization (Clic here for more details about this article) |
3/7. Lymphoepithelioma-like carcinoma of the breast. An unusual pattern of infiltrating lobular carcinoma.A case of breast carcinoma, showing both lymphoepithelioma-like and lobular infiltrating carcinoma, is described, which must be distinguished from the medullary carcinoma with which it shares some features, such as the strong lymphocytic infiltration, but not sharp circumscription, syncytial growth pattern, nuclear pleomorphism, and high mitotic rate. Unlike the lymphoepithelial carcinoma of the nasopharynx and some lympho-epithelioma-like carcinomas of the lung, stomach, salivary glands, and thymus, it does not seem to be connected with Epstein-Barr virus (EBV) infection, as shown by negative results of both in situ hybridization and polymerase chain reaction. This neoplasia may be defined as a peculiar form of lobular carcinoma, therefore, more representative of an unusual microscopic pattern than a distinctive clinicopathologic entity in itself.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
4/7. A case of metastatic breast cancer with outgrowth of HER2-negative cells after eradication of HER2-positive cells by humanized anti-HER2 monoclonal antibody (trastuzumab) combined with docetaxel.A 38-year-old woman with cancer of the left breast underwent a modified radical mastectomy with lymph node dissection. Twenty-one months later, massive liver metastases and pleural carcinomatosis occurred. The liver metastases responded completely to chemotherapy with trastuzumab combined with docetaxel, but the pleural carcinomatosis was refractory to the therapy. fluorescence in situ hybridization showed that both the primary tumor and the metastatic tumors of the lymph nodes were composed of HER2 amplification-positive and HER2 amplification-negative cancer cells. This analysis also detected a single cell with HER2 amplification in the pleural effusion that was taken at the completion of the chemotherapy, but four follow-up tests showed no amplified cells. It is speculated that in the liver metastases, the trastuzumab was cytotoxic to both HER2-amplified and nonamplified cancer cells and may have acted through its antiangiogenic effect. However, in the pleural effusion, the effect of trastuzumab was more specific to HER2-amplified cells and caused outgrowth of cancer cells lacking expression of HER2 receptors.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
5/7. HER2 and central nervous system metastasis in patients with breast cancer.We report a case of a patient who developed a central nervous system (CNS) metastasis 17 months after surgery and adjuvant therapy for stage II breast cancer. The HER2 status of the primary tumor as determined by immunohistochemistry (IHC) was 1 , and fluorescence in situ hybridization (FISH) performed retrospectively showed a borderline-negative result (ratio, 1:9), although HER2 amplification was present in a minority of breast cancer cells. By contrast, the HER2 status of the CNS metastasis was positive by IHC (3 ) and FISH (ratio, 3:7). This report discusses the possibility that, for metastatic invasion into the CNS, clonal selection may occur, favoring HER2-positive cell clones.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
6/7. Clinical application of array-based comparative genomic hybridization to define the relationship between multiple synchronous tumors.Array-based comparative genomic hybridization (CGH) is a technique that allows genome wide screening of gains and losses in dna copy number. In cases where multiple tumors are encountered, this genetic technique may prove useful in differentiating new primary tumors from recurrences. In this case report, we used array-based CGH to examine the genomic relationships among two leiomyosarcomas and two breast cancers in the same patient, three of which were diagnosed synchronously. Array-based CGH was performed on the four tumor samples using random prime amplified microdissected dna. Samples were hybridized onto bacterial artificial chromosome arrays composed of approximately 2400 clones. Patterns of alterations within the tumors were compared and genetic alterations among the leiomyosarcomas and breast lesions were found. overall, three distinct genetic profiles were observed. While the two leiomyosarcomas shared a similar pattern of genetic alterations, the two invasive breast lesions did not. The nearly identical pattern of genetic alterations belonging to the two metachronous leiomyosarcomas confirmed metastatic recurrence while the two different genetic profiles of the invasive ductal carcinomas suggest that the two lesions represented two distinct foci of multifocal disease rather than clonal extension of the primary tumor. We conclude that genetic analysis by array-based CGH can clearly elucidate the relationships between multiple tumors and may potentially serve as an important clinical tool.- - - - - - - - - - ranking = 5keywords = hybridization (Clic here for more details about this article) |
7/7. Detection of alterations in chromosomes 16 and 1 by fluorescence in situ hybridization in breast tumors cytologically or histologically equivocal for malignancy.Structural and numerical alterations, and fusion of chromosomes 16 and 1 have been shown to occur frequently in low-grade breast carcinoma, but not in benign papilloma by fluorescence in situ hybridization (FISH). We carried out FISH analysis of 11 benign tumors and 3 breast tumors for which the preoperative diagnosis was equivocal for cancer. In 11 benign lesions and 1 benign phyllode tumor which was cytologically equivocal for malignancy, alteration of the chromosome 16 or 1 signal was not detected as a predominant cell clone. On the other hand, in 1 grade 1 invasive ductal carcinoma which was judged as equivocal for malignancy and 1 marked adenosis with atypia which was judged as malignant by fine-needle aspiration cytology, the majority of constituent tumor cells showed fusion of chromosomes 16 and 1. Detection of alterations in chromosomes 16 and 1 as a predominant clone was suggested to be an indicator of lesion malignancy even though the grade of malignancy may not be high. As a supportive diagnostic procedure, FISH analysis may give information about the nature of lesions, when the lesions are clinically or pathologically equivocal for cancer.- - - - - - - - - - ranking = 5keywords = hybridization (Clic here for more details about this article) |