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Biomedical subjects

Elizabeth Perlman

Publications and source records attributed to Elizabeth Perlman.

8 recordsLinked to original sources
PubMed2007

Treatment of Wilms tumor relapsing after initial treatment with vincristine and actinomycin D: a report from the National Wilms Tumor Study Group.

PURPOSE: NWTS-5 was a multi-institutional clinical trial for patients less than 16 years of age at diagnosis with specific renal neoplasms who were diagnosed between August 1, 1995 and May 31, 2002. A uniform approach to the treatment of patients with relapse was employed. PATIENTS AND METHODS: Seventy-two patients who relapsed after immediate nephrectomy (stages I and II), initial chemotherapy with vincristine (VCR) and actinomycin D and no radiation therapy were registered on stratum B of the NWTS-5 relapse protocol. Four patients were not evaluable: one due to insufficient data and three due to major protocol violations. Among the 68 remaining patients, one who was 19 years of age at initial diagnosis of Wilms tumor, five with bilateral Wilms tumor at diagnosis, three who developed a contralateral relapse, and one with persistent disease were not included in this analysis. Relapse treatment included surgical excision, when feasible, radiation therapy and alternating courses of VCR, doxorubicin and cyclophosphamide and etoposide and cyclophosphamide. RESULTS: The outcomes of 58 patients were analyzed. The lung was the only site of relapse for 31 patients. Event-free survival 4 years after relapse was 71.1% and 4-year overall survival was 81.8% for all patients and were 67.8 and 81.0% for those who relapsed only to their lungs. The most frequent toxicities were hematological. CONCLUSIONS: These results demonstrate that a significant proportion of children with Wilms tumor who relapse after initial treatment with VCR and actinomycin D can be successfully re-treated.

Antibiotics, Antineoplastic↗
PubMed2005

Rhabdoid tumor of the kidney in the National Wilms' Tumor Study: age at diagnosis as a prognostic factor.

PURPOSE: The objective of this study is to determine prognostic factors in rhabdoid tumor of the kidney (RTK), including both demographic and treatment variables. PATIENTS AND METHODS: A total of 142 patients studied on National Wilms' Tumor Studies 1, 2, 3, 4, and 5 were analyzed. Patients were enrolled between the years 1969 and 2002. Variables examined included sex, age of diagnosis, tumor stage, presence of CNS lesions, as well as treatment variables, including the use of doxorubicin and/or radiotherapy (RT). RESULTS: No survival differences were observed between males and females, between those treated with or without doxorubicin, or with or without RT. Patients with tumors of lower stage had an overall survival rate of 41.8%, whereas, tumors of higher stage were associated with a 15.9% survival (P < .001). A highly significant difference in survival was noted when patients were stratified according to age of diagnosis. Survival at 4 years in infants under 6 months of age at diagnosis was 8.8%, whereas, survival in patients 2 years of age or older was 41.1% (P < .0001). Stratification into intermediate age brackets demonstrated a strong correlation of increasing survival with increasing age at diagnosis. All patients with a CNS lesion, except one, died. CONCLUSION: Age at diagnosis is a highly significant prognostic factor for survival of children with RTK. Infants have a dismal prognosis, whereas, older children have a more favorable outcome. Higher tumor stage and presence of a CNS lesion were both factors predictive of a poor survival rate.

Age Distribution↗
PubMed2005

Loss of heterozygosity for chromosomes 1p and 16q is an adverse prognostic factor in favorable-histology Wilms tumor: a report from the National Wilms Tumor Study Group.

PURPOSE: To determine if tumor-specific loss of heterozygosity (LOH) for chromosomes 1p or 16q is associated with a poorer prognosis for children with favorable-histology (FH) Wilms tumor entered on the fifth National Wilms Tumor Study (NWTS-5). PATIENTS AND METHODS: Between August 1995 and June 2002, 2,021 previously untreated children with FH or anaplastic Wilms tumor, clear-cell sarcoma of the kidney (CCSK) or malignant rhabdoid tumor of the kidney (RTK), were treated with stage- and histology-specific therapy. Their tumors were assayed for LOH for polymorphic DNA markers on chromosomes 1p and 16q. ResultsLOH for 1p or 16q was rarely observed in CCSK (n = 90) or RTK (n = 22). The relative risk (RR) of relapse for patients with FH stage I to IV tumors with LOH, stratified by stage, was 1.56 for LOH 1p (P = .01) and 1.49 for LOH 16q (P = .01), whereas the RR of death was 1.84 (P = .03) and 1.44 (P = .15), respectively. When the effects of LOH for both regions were considered jointly among patients with stage I to II FH disease, the risks of relapse and death were increased for LOH 1p only (RR = 2.2, P = .02 for relapse; RR = 4.0, P = .02 for death), for LOH 16q only (RR = 1.9, P = .01 and RR = 1.4, P = .60) and for LOH for both regions (RR = 2.9, P = .001 and RR = 4.3, P = .01) in comparison with patients with LOH at neither locus. The risks of relapse and death for patients with stage III to IV FH tumors were increased only with LOH for both regions (RR = 2.4, P = .01 and RR = 2.7, P = .04). CONCLUSION: Tumor-specific LOH for both chromosomes 1p and 16q identifies a subset of FH Wilms tumor patients who have a significantly increased risk of relapse and death. LOH for these chromosomal regions can now be used as an independent prognostic factor together with disease stage to target intensity of treatment to risk of treatment failure.

Child↗
PubMed2004

Treatment outcomes in adults with favorable histologic type Wilms tumor-an update from the National Wilms Tumor Study Group.

PURPOSE: To describe the clinical outcomes in adults with favorable histologic type (FH) Wilms tumor (WT) registered in the National Wilms Tumor Studies (NWTS) 4-5. We also describe the results of patients treated in the "modern era" (1979-2001) with surgical staging, central pathology review and stage-appropriate multimodality treatment. METHODS AND MATERIALS: Twenty-three adult patients (> or =16 years of age) with FHWT after central pathology review were registered on NWTS 4-5. The tumor stage distribution was Stage I in 5, Stage II in 8, Stage III in 6, and Stage IV in 4 patients. All patients underwent primary nephrectomy followed by multiagent chemotherapy and/or radiotherapy (RT). All patients underwent tumor stage-based chemotherapy that generally followed existing NWTS Group (NWTSG) protocols. To analyze the outcomes of adult patients treated in the "modern era," the data from this report were combined with the data from 22 patients with FHWT previously reported in 1990 by the NWTSG. RESULTS: The 5-year relapse-free survival, overall survival, and disease-specific survival (DSS) rate was 77.3%, 82.6%, and 95.7%, respectively, for patients registered in the NWTS 4-5 protocols. Three patients (13%) died of chemotherapy-induced hepatic venoocclusive disease. For a total of 45 adults with FHWTs treated in the "modern era," the overall survival rate was 82%. The survival rate for those with Stage I, II, III, and IV disease was 100%, 92%, 70%, and 73%, respectively. Of the 12 Stage I-II patients treated with two drugs and no RT, the survival rate was 100%. The survival rate for Stage III and IV patients treated with three drugs and RT was 63% and 70%, respectively. CONCLUSION: The results of this report demonstrate that adults with FHWT treated with a multimodality approach similar to NWTSG protocols have good survival. We recommend that all adult patients be treated with stage-appropriate combined modality therapy, and furthermore, be entered in current Children's Oncology Group WT protocols so that coherent data can be gathered for this relatively rare tumor. Finally, all patients should be monitored for signs and symptoms of hepatic venoocclusive disease.

Adolescent↗
PubMed2002

Mucinous cancers have fewer genomic alterations than more common classes of breast cancer.

Mucinous cancers of the breast are distinguished histologically by their abundant pools of mucin and low degree of nuclear pleomorphism. Relative to the more common breast cancers of no distinctive type (ductal carcinoma), mucinous cancers have a relatively favorable prognosis. In a study of chromosomal changes in mucinous cancers, we evaluated the extent of loss of heterozygosity (LOH) at chromosomal regions commonly deleted in usual infiltrating ductal carcinoma, including markers on chromosomal arms 1p, 1q, 3p, 6q, 8p, 9p, 11p, 11q, 13q, 16q, 17p, and 17q. Remarkably, we found an average frequency of LOH of only 1.9 of these 12 chromosomal arms in 18 cases of mucinous carcinoma, compared to an average frequency of LOH of 6.4 of these same chromosomal arms in cases of infiltrating ductal cancer. In three of the 18 cases of mucinous carcinoma studied, including one case with regional lymph node metastases, no LOH was seen at any of the 12 chromosomal regions studied. We considered the possibility of other chromosomal loci being more commonly affected in mucinous cancers and conducted comparative genomic hybridization on six of the cases. These studies demonstrated a low overall frequency of genomic copy number changes (mean of 3.1 changes per case) and failed to reveal any other chromosomal locus with frequent losses that had not been evaluated by microsatellite analysis. Together, these data indicate that mucinous cancers of the breast do not have the extensive genomic alterations that are typically found in more common variants of breast cancer. Thus, mucinous cancers most likely have less genetic instability than most other forms of breast cancer and the molecular pathogenesis of this form of breast cancer is likely to be substantially different than that of usual ductal breast cancer.

Adenocarcinoma, Mucinous↗
PubMed2002

Micropapillary serous carcinoma of the ovary has distinct patterns of chromosomal imbalances by comparative genomic hybridization compared with atypical proliferative serous tumors and serous carcinomas.

Recent studies have subdivided serous borderline tumors into 2 categories: atypical proliferative serous tumors (APSTs), which have a relatively benign course, and micropapillary serous carcinomas (MPSCs), which behave like low-grade carcinoma. This study was undertaken to determine, using comparative genomic hybridization (CGH), whether cytogenetic changes support this hypothesis. Nine cases of APST, 10 of MPSC, and 11 of invasive serous carcinoma (SC) were analyzed by CGH. Tumor DNA was extracted from frozen or paraffin-embedded tissue from the primary ovarian tumor, using either sections with at least 70% tumor cells or tissue after relative enrichment by microdissection. Chromosomal imbalances were identified in 3 of 9 APST, 6 of 10 MPSC, and 11 of 11 SC. Three or more chromosomal imbalances were found in 0 of 9 APST, 4 of 10 MPSC, and 9 of 11 SC. Recurrent copy number alterations were grouped into 4 classes correlating with the different tumor types. Class I changes were present in APST and in MPSC or SC and included +8q (7 of 11 SC, 2 of 10 MPSC, 2 of 9 APST), -9p (5 of 11 SC, 0 of 10 MPSC, 1 of 9 APST), and +12 (+12p in 3/11 SC, +12 in 2 of 10 MPSC, +12 in 1 of 9 APST). Class II changes were found only in MPSC and SC, but not in APST. The most frequent examples were +3q (10 of 11 SC, 1 of 10 MPSC), -4q (5 of 11 SC, 1 of 10 MPSC), and -17p (5 of 11 SC, 1 of 10 MPSC). Class III changes were limited to SC, like -16q (7 of 11 SC) and -18q (6 of 11 SC). Class VI changes were unique to MPSC. Gain of 16p (3 of 10 MPSC) was the only aberration in this group. This aberration was not only unique to MPSC but was also the most frequent finding in MPSC. These data support the hypothesis that noninvasive serous tumors of the ovary can be subdivided into 2 categories: APST and MPSC. The number of imbalances in MPSC is substantially higher than in APST and lower than in SC. Some changes in MPSC are shared with SC and APST and others with SC only, suggesting that a subset of MPSC may represent a stage in progression from APST to SC. Other cases of MPSC with independent genetic alterations may represent another subset of tumors that are a distinct entity from APST and SC.

Adolescent↗
PubMed2002

A genome-wide screen for normally methylated human CpG islands that can identify novel imprinted genes.

DNA methylation is a covalent modification of the nucleotide cytosine that is stably inherited at the dinucleotide CpG by somatic cells, and 70% of CpG dinucleotides in the genome are methylated. The exception to this pattern of methylation are CpG islands, CpG-rich sequences that are protected from methylation, and generally are thought to be methylated only on the inactive X-chromosome and in tumors, as well as differentially methylated regions (DMRs) in the vicinity of imprinted genes. To identify chromosomal regions that might harbor imprinted genes, we devised a strategy for isolating a library of normally methylated CpG islands. Most of the methylated CpG islands represented high copy number dispersed repeats. However, 62 unique clones in the library were characterized, all of which were methylated and GC-rich, with a GC content >50%. Of these, 43 clones also showed a CpG(obs)/CpG(exp) >0.6, of which 30 were studied in detail. These unique methylated CpG islands mapped to 23 chromosomal regions, and 12 were differentially methylated regions in uniparental tissues of germline origin, i.e., hydatidiform moles (paternal origin) and complete ovarian teratomas (maternal origin), even though many apparently were methylated in somatic tissues. We term these sequences gDMRs, for germline differentially methylated regions. At least two gDMRs mapped near imprinted genes, HYMA1 and a novel homolog of Elongin A and Elongin A2, which we term Elongin A3. Surprisingly, 18 of the methylated CpG islands were methylated in germline tissues of both parental origins, representing a previously uncharacterized class of normally methylated CpG islands in the genome, and which we term similarly methylated regions (SMRs). These SMRs, in contrast to the gDMRs, were significantly associated with telomeric band locations (P =.0008), suggesting a potential role for SMRs in chromosome organization. At least 10 of the methylated CpG islands were on average 85% conserved between mouse and human. These sequences will provide a valuable resource in the search for novel imprinted genes, for defining the molecular substrates of the normal methylome, and for identifying novel targets for mammalian chromatin formation.

Amino Acid Sequence↗