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MCF-7/AdrVp is a multidrug-resistant human breast cancer subline that displays an ATP-dependent reduction in the intracellular accumulation of anthracycline anticancer drugs in the absence of overexpression of known multidrug resistance transporters such as P glycoprotein or the multidrug resistance protein. RNA fingerprinting led to the identification of a 2.4-kb mRNA that is overexpressed in MCF-7/AdrVp cells relative to parental MCF-7 cells. The mRNA encodes a 663-aa member of the ATP-binding cassette superfamily of transporters that we term breast cancer resistance protein (BCRP). Enforced expression of the full-length BCRP cDNA in MCF-7 breast cancer cells confers resistance to mitoxantrone, doxorubicin, and daunorubicin, reduces daunorubicin accumulation and retention, and causes an ATP-dependent enhancement of the efflux of rhodamine 123 in the cloned transfected cells. BCRP is a xenobiotic transporter that appears to play a major role in the multidrug resistance phenotype of MCF-7/AdrVp human breast cancer cells.

Context.--Methods for plasma cell enrichment of bone marrow (BM) specimens can increase the sensitivity of fluorescence in situ hybridization (FISH) for detecting cytogenomic abnormalities. There are no published reports using these methods to evaluate high-risk cytogenomic abnormalities in patients with plasma cell neoplasms (PCNs) after therapy. Objective.--To evaluate the utility of plasma cell enrichment combined with FISH for detection of high-risk cytogenomic abnormalities in patients with PCNs after therapy. Design.--Twenty-eight patients with PCNs, of whom 22 received treatment, were included in this study. Plasma cells were enriched in BM aspirates by using a magnetic cell-sorting procedure to select [CD138.sup.+] cells. Probes were chosen to assess for del(17p13/7P53), del(13q14/RB7), 1q21/CKS1B gain, IgH/FGFR3, and IgH/MAF. Clinicopathologic data were collected during clinical follow-up after plasma cell enrichment. Results.--Plasma cells in nonenriched BM specimens ranged from 1% to 28% (median, 8%) compared with 28% to 96% (median, 73%) in enriched BM specimens (P < .001). In a subset of treated patients in clinical remission, FISH detected high-risk cytogenomic abnormalities only in plasma cell-enriched samples. This approach also detected abnormalities in cases of solitary plasmacytoma and monoclonal gammopathy of undetermined significance. Conclusions.--Plasma cell enrichment of BM specimens increases FISH sensitivity for detecting high-risk cytogenomic abnormalities, particularly in treated patients, and these results, in combination with clinical follow-up data, can be of value to improve risk stratification and patient management. (Arch Pathol Lab Med. 2013;137:625-631; doi: 10.5858/arpa.2012-0209-OA), Plasma cell myeloma (PCM) is the most common type of plasma cell neoplasm (PCN), diagnosed in approximately 20 000 patients each year in the United States. Among patients with monoclonal [...]

* Context.--Li-Fraumeni syndrome (LFS), characterized by predisposition to early onset of a variety of malignancies, is usually associated with germline mutation of the tumor-suppressor gene, TP53. Mutation carriers are at increased risk of multiple primary tumors, many of which arise in previous radiation-therapy sites. In patients with LFS, acute myeloid leukemia is uncommon and myelodysplastic syndrome (MDS) is rare. Objective.--To evaluate the morphologic, cytogenetic, and molecular diagnostic findings of 3 unique cases of MDS arising in patients with germline TP53 mutation, 2 with classic LFS. Design.--We searched the Li-Fraumeni Syndrome Registry in the Department of Genetics at the University of Texas M. D. Anderson Cancer Center (Houston, Texas) and identified 3 patients with documented germline TP53 mutations or LFS who had developed MDS during a period of 6 years (2000-2005). The clinical, cytogenetic, and molecular diagnostic data and bone marrow aspirate smears and biopsies on all patients were reviewed. Immunohistochemical staining with antibody to p53 was also performed. Results.--Two patients met the criteria for classic LFS; one had no history of malignancy in first-degree relatives. The MDS followed chemotherapy and radiation therapy and progressed to acute myeloid leukemia in 2 patients. Cytogenetic analysis demonstrated chromosome 5 abnormalities in a complex karyotype in all cases. Two patients died, one of acute myeloid leukemia and one with glioblastoma multiforme, MDS, and persistent pancytopenia. Conclusions.--Patients with LFS may develop MDS, which is most likely therapy-related and is associated with cytogenetic markers of poor prognosis., Li-Fraumeni syndrome (LFS), a rare autosomal dominant syndrome first described by Li and Fraumeni in 1969, (1) is characterized by a high incidence of a variety of malignant neoplasms in [...]

* Primary follicular lymphoma of the testis in childhood is extremely rare. To our knowledge, only 5 cases have been reported to date. We report a case in a 6-year-old boy who presented with painless right scrotal enlargement. Right radical orchiectomy revealed a follicular large cell lymphoma with diffuse areas confined to the testis and epididymis, clinical stage IE. Immunohistochemical stains demonstrated that the neoplastic cells were of B-cell lineage, positive for CD10, CD20, CD79a, and BCL-6. Staining for CD21 accentuated networks of dendritic reticulum cells within the nodules. The cells were negative for BCL-2, p53, and T-cell antigens. There was no evidence of the t(14;18) detected by polymerase chain reaction. The data suggest that follicular lymphoma of the testis in children has a different pathogenesis than follicular lymphoma in adults. (Arch Pathol Lab Med. 2001;125:551-554), Malignant lymphoma of follicle center origin is one of the most common types of non-Hodgkin lymphoma (NHL) in the United States. It accounts for approximately 20% to 30% of cases [...]

Non-Hodgkin lymphoma arising in the paratesticular organs without testicular involvement is rare. In most previously reported cases, the classification systems that were used are now outdated and/or immunologic studies were not done. We report the clinical and pathologic features of 2 cases of non-Hodgkin lymphoma arising in the epididymis and the spermatic cord. Patient I was a 35-year-old man who presented with a painless scrotal mass. Patient 2 was a 61-year-old man who presented with a right inguinal mass. Orchiectomy performed in both patients revealed a mass confined to the epididymis in patient 1 and to the spermatic cord in patient 2. Histologic examination in both cases revealed diffuse large cell lymphoma, and immunohistochemical studies supported B-cell lineage. Subsequent staging studies showed no other site of disease in patient I and an isolated mass anterior to the right psoas muscle in patient 2. Malignant lymphoma involving testicular adnexal structures without involvement of the testis is extremely uncommon. To our knowledge, only 6 cases confined to the epididymis and 12 cases confined to the spermatic cord have been reported previously. (Arch Pathol Lab Med. 2001;125:428-432), A Report of 2 Cases and Review of the Literature Testicular lymphoma is an aggressive extranodal non-Hodgkin lymphoma (NHL) that frequently invades the tunica albuginea, rete testis, epididymis, and spermatic [...]

Abstract. When injected into mice, the synthetic double-stranded polynucleotide poly(inosinic) * poly(cytidylic) acid induces high natural killer (NK) cell activity within 4 to 12 hours. Induction of NK activity in […]