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P Thorner

Publications and source records attributed to P Thorner.

At least 19 recordsLinked to original sources
PubMed2005

Evidence for an age cutoff greater than 365 days for neuroblastoma risk group stratification in the Children's Oncology Group.

PURPOSE: In the Children's Oncology Group, risk group assignment for neuroblastoma is critical for therapeutic decisions, and patients are stratified by International Neuroblastoma Staging System stage, MYCN status, ploidy, Shimada histopathology, and diagnosis age. Age less than 365 days has been associated with favorable outcome, but recent studies suggest that older age cutoff may improve prognostic precision. METHODS: To identify the optimal age cutoff, we retrospectively analyzed data from the Pediatric Oncology Group biology study 9047 and Children's Cancer Group studies 321p1-p4, 3881, 3891, and B973 on 3,666 patients (1986 to 2001) with documented ages and follow-up data. Twenty-seven separate analyses, one for each different age cutoff (adjusting for MYCN and stage), tested age influence on outcome. The cutoff that maximized outcome difference between younger and older patients was selected. RESULTS: Thirty-seven percent of patients were younger than 365 days, and 64% were > or = 365 days old (4-year event-free survival [EFS] rate +/- SE: 83% +/- 1% [n = 1,339] and 45% +/- 1% [n = 2,327], respectively; P < .0001). Graphical analyses revealed the continuous nature of the prognostic contribution of age to outcome. The optimal 460-day cutoff we selected maximized the outcome difference between younger and older patients. Forty-three percent were younger than 460 days, and 57% were > or = 460 days old (4-year EFS rate +/- SE: 82% +/- 1% [n = 1,589] and 42% +/- 1% [n = 2,077], respectively; P < .0001). Using a 460-day cutoff (assuming stage 4, MYCN-amplified patients remain high-risk), 5% of patients (365 to 460 days: 4-year EFS 92% +/- 3%; n = 135) fell into a lower risk group. CONCLUSION: The prognostic contribution of age to outcome is continuous in nature. Within clinically relevant risk stratification, statistical support exists for an age cutoff of 460 days.

Age Factors↗
PubMed2004

High-resolution cDNA microarray CGH mapping of genomic imbalances in osteosarcoma using formalin-fixed paraffin-embedded tissue.

Formalin-fixed paraffin embedded (FFPE) tumor tissue provides an opportunity to perform retrospective genomic studies of tumors in which chromosomal imbalances are strongly associated with oncogenesis. The application of comparative genomic hybridization (CGH) has led to the rapid accumulation of cytogenetic information on osteosarcoma (OS); however, the limited resolving power of metaphase CGH does not permit precise mapping of imbalances. Array CGH allows quantitative detection and more precise delineation of copy number aberrations in tumors. Unfortunately the high cost and lower density of BACs on available commercial arrays has limited the ability to comprehensively profile copy number changes in tumors such as OS that are recurrently subject to genomic imbalance. In this study a cDNA/EST microarray including 18,980 human cDNAs (which represent all 22 pairs of autosomal chromosomes and chromosome X) was used for CGH analysis of eight OS FFPE. Chromosomes 1, 12, 17, and X harbored the most imbalances. Gain/amplification of X was observed in 4/8 OS, and in keeping with other recent genomic analyses of OS, gain/amplification of 17p11.2 was often accompanied by a distal deletion in the region of the p53 gene. Gain/amplification of the X chromosome was verified using interphase FISH carried out on a subset of OS FFPE sections and OS tissue arrays.

Adolescent↗
PubMed2002

Prognostic impact of chromosomal aberrations in Ewing tumours.

Although greater than 50% of Ewing tumours contain non-random cytogenetic aberrations in addition to the pathognomonic 22q12 rearrangements, little is known about their prognostic significance. To address this question, tumour samples from 134 Ewing tumour patients were analysed using a combination of classical cytogenetics, comparative genomic and fluorescence in situ hybridisation. The evaluation of the compiled data revealed that gain of chromosome 8 occurred in 52% of Ewing tumours but was not a predictive factor for outcome. Gain of 1q was associated with adverse overall survival and event-free survival in all patients, irrespective of whether the tumour was localised or disseminated (overall survival: P=0.002 and P=0.029; event-free survival: P=0.018 and P=0.010). Loss of 16q was a significant predictive factor for adverse overall survival in all patients (P=0.008) and was associated with disseminated disease at diagnosis (P=0.039). Gain of chromosome 12 was associated with adverse event-free survival (P=0.009) in patients with localised disease. These results indicate that in addition to a 22q12 rearrangement confirmation in Ewing tumours it is important to assess the copy number of 1q and 16q to identify patients with a higher probability of adverse outcome.

Adult↗
PubMed2002

Tyrosine phosphorylation in human lymphomas.

In a previous study, we showed that the high level of protein tyrosine phosphorylation present in lymphomas containing an anaplastic lymphoma kinase (ALK) can be demonstrated in routinely processed paraffin tissue sections using immunolabelling techniques. In the present study we investigated whether oncogenic tyrosine kinase activation also occurs in other categories of lymphoma by staining 145 cases of lymphoma covering those tumours with a range of different subtypes including those with morphological similarity to ALK-positive anaplastic large cell lymphoma (ALCL). Twelve cases of the borderline malignant disorder lymphomatoid papulosis were also studied. Twenty seven of the 28 cases of ALK-positive ALCL showed the extensive cytoplasmic labelling for phosphotyrosine in the neoplastic cells. The remaining case containing moesin-ALK exhibited membrane-associated phosphotyrosine expression. There was no nuclear phosphotyrosine labelling in any of the ALK-positive ALCL, even though ALK was present within the cell nuclei in 23 of the tumours. Variable degrees of phosphotyrosine labelling, usually membrane-restricted, were observed in 7/40 cases of ALK-negative ALCL, 9/29 cases of diffuse large B-cell lymphoma, 3/6 cases of mediastinal B-cell lymphoma, 2/7 cases of Hodgkin's lymphoma, 3/6 cases of peripheral T-cell lymphomas unspecified, 4/6 cases of B-cell chronic lymphocytic leukaemia, 2/6 cases of follicular lymphomas and 2/12 cases of lymphomatoid papulosis studied. However none of these phosphotyrosine-positive cases showed the strong cytoplasmic labelling comparable to that seen in ALK-positive lymphoma. We conclude that activation of a tyrosine kinase is probably not a major oncogenic event in lymphomas other than ALK-positive ALCL.

Cell Nucleus↗
PubMed2001

Comparative genomic hybridization analysis identifies gains of 1p35 approximately p36 and chromosome 19 in osteosarcoma.

Osteosarcomas (OS) are aggressive tumors of the bone and often have a poor prognosis. Conventional cytogenetic analyses of OS have revealed highly complex karyotypes, with numerous abnormalities. In this study, we analyzed 18 untreated OS tumors from 17 patients of the younger incidence age group by comparative genomic hybridization (CGH), 4 tumors by spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH). Comparative genomic hybridization identified frequent copy number changes of the chromosomal region 1p (10/17) and gain of part or all of chromosome 19(8/17). In addition gains were observed at 5p(3/17), 8q(3/17), 16p(3/17), and 17p(5/17); and losses at chromosomes 2q(3/17), 10(4/17) and 13(3/17). High level gains were detected in the 8q23 approximately q24 region in two tumors as well as at 17p in one primary and a metastatic tumor. Minimal regions of gain were present at 1p35 approximately p36.3 (8/17); 5p14 approximately p15.2 (3/17), and 8q22 approximately q24.3 (3/17). SKY analysis demonstrated that OS has a complex pattern of clonal and non-clonal rearrangements and helped confirm the structural basis for the imbalances detected by CGH. Spectral karyotyping confirmed an overall pattern of chromosomal gain affecting 1p in all four tumors. Fluorescence in situ hybridization analysis from these tumors confirmed the gain of the 1p36 region in 2 tumors as determined by CGH analysis as well as the amplification of 8q.

Bone Neoplasms↗
PubMed2001

Acquisition of secondary structural chromosomal changes in pediatric ewing sarcoma is a probable prognostic factor for tumor response and clinical outcome.

BACKGROUND: The Ewing sarcoma (ES) group of tumors commonly have the t(11;22)(q24;q12) or other rearrangements involving 22q12. In addition to these consistent aberrations, both numeric and structural aberrations have been reported: namely gains of chromosomes 8 and 12, the unbalanced translocation t(1;16), and deletions at the short arm of chromosome 1. METHODS: To evaluate the frequency and to study the prognostic implications of some of these aberrations in children, the authors performed a pilot study of 26 ES pediatric patients by classic cytogenetics and/or interphase fluorescence in situ hybridization (FISH) and compared these data with clinical parameters. RESULTS: Gains of chromosomes 8 and 12 were detected, by interphase FISH, in 48% (10 of 21) and 38% (6 of 16) of the tumors, respectively, and this was not significant with respect to treatment response. Statistical analysis revealed that the presence of additional secondary structural chromosomal aberrations was associated with an unfavorable outcome (P = 0.0034 as an independent prognostic value as an unfavorable marker). Presence of metastasis at diagnosis also was found to be associated with poor outcome (P = 0.0131). Spectral karyotyping analysis was shown to facilitate the detection of more complex structural chromosomal aberrations in a representative ES tumor. CONCLUSIONS: It is important to determine whether additional structural chromosomal aberrations are present in ES tumors because it appears that a more complex karyotype with multiple chromosomal aberrations is associated with poor outcome in ES.

Adolescent↗
PubMed2001

Ophthalmic involvement as a presenting feature of nonorbital childhood parameningeal embryonal rhabdomyosarcoma.

OBJECTIVE: To describe presenting ophthalmic signs and symptoms in children with parameningeal rhabdomyosarcoma. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Twenty-three children with parameningeal rhabdomyosarcoma treated from 1978 through 1998. MAIN OUTCOME MEASURES: Each patient's presenting symptoms and history, the ophthalmic signs at presentation, the location of the tumor on computed tomographic scanning, the pathologic diagnosis after tumor biopsy, and the child's outcome after chemotherapy and radiotherapy. RESULTS: Eight of 23 patients with parameningeal rhabdomyosarcoma had ophthalmologic signs at presentation. All patients had sixth nerve palsies, and four had additional third nerve palsies. Fifth and seventh nerve involvement was seen in three children each, and two manifested additional fourth nerve palsies. In two patients, invasion of the optic canals and posterior orbit resulted in unilateral blindness in one and marked unilateral visual loss in the other. In no patient was the symptomatic history longer than 12 weeks. Seven of eight patients were treated with a combination of surgery, chemotherapy, and radiotherapy. The mean survival time for five patients who died from parameningeal rhabdomyosarcoma associated with ophthalmic signs was 27.2 months. Three patients are currently alive, with a mean survival time of 33.7 months after diagnosis. The survival time of 12 patients with parameningeal rhabdomyosarcoma and without ophthalmologic signs at presentation was better, in that nine are alive, with a mean survival time of 54 months. CONCLUSIONS: Advanced parameningeal rhabdomyosarcoma with skull base invasion may present with ophthalmic signs. These patients sought treatment late and had advanced tumors because their initial signs and symptoms were often attributed to more common ailments. Usually, the onset of the cranial nerve palsy initiated referral to the tertiary care center. The sixth nerve was the most vulnerable. Further invasion of the skull base or cavernous sinus may cause additional third, fourth, and fifth nerve palsies. The optic nerve was involved when the optic canals and orbit were encroached on by the tumor. The prognosis for survival was poor when these tumors were accompanied by ophthalmic signs.

Child↗
PubMed2001

In vivo identification of Langerhans and related dendritic cells infected with HIV-1 subtype E in vaginal mucosa of asymptomatic patients.

In Thailand, the predominant HIV subtype is E, rather than Subtype B as in North America and Europe, and the predominant mode of transmission is heterosexual contact. Subtype E has the ability to replicate in vitro in Langerhans cells. We hypothesized that this cell type might constitute a reservoir for the HIV virus in vaginal mucosa of asymptomatic carriers. To examine this hypothesis, we compared vaginal tissue histology in HIV-1-seropositive cases with seronegative cases and determined the immunophenotype of HIV-1-infected cells, their numbers, and their distribution in vaginal mucosa. Vaginal biopsies were performed at four different sites from six asymptomatic HIV-1 Subtype E-infected persons and from six seronegative cases at necropsy and examined histologically. Immunophenotyping was performed using immunoperoxidase for Gag p24 HIV, CD3, CD20, CD68, CD1a, S-100 and p55 antigens and by double labeling, combining immunoperoxidase with alkaline phosphatase using pairs of the above antigens. Twenty of twenty-four vaginal biopsies (83.3%) from HIV-seropositive cases showed definite inflammation compared to five of twenty-four vaginal necropsies (20.8%) from HIV-seronegative cases. One third of HIV-seropositive biopsies (8/24) demonstrated p24-positive cells in the epithelium, whereas three-fourths (18/24) of the biopsies revealed p24-positive cells in the lamina propria. All seropositive patients showed positive cells in at least one biopsy, but not all biopsies contained positive cells. Infected cells were more frequently observed at sites of greater inflammation. The dendritic cell count in HIV-seropositive vaginal epithelium was significantly higher than that observed in the seronegative cases (P =.004). The majority of p24-positive cells in the vaginal epithelium were Langerhans cells (CD1a+/S-100+), whereas in the lamina propria, about half of p24-positive cells were Langerhans-related dendritic cells (p55+ and S-100+) and half were T lymphocytes. In conclusion, the increased propensity for heterosexual transmission of Subtype E may be related to vaginal inflammation, leading to the accumulation of Langerhans cells and related dendritic cells which, once infected with HIV, can act as a reservoir for further virus transmission.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Establishment of a cytokine-producing anaplastic large-cell lymphoma cell line containing the t(2;5) translocation: potential role of cytokines in clinical manifestations.

A permanent cell line, HSC-M1, was established from a child with advanced CD30 (Ki-1)+ anaplastic large-cell lymphoma (ALCL). Clinical features included irritability, fever, weight loss, tender lymphadenopathy, pneumonitis, neutrophilia, and bone marrow erythrophagocytosis. While HSC-M1 cells exhibited an immunophenotype characteristic of ALCL of T-cell lineage, the cell line also demonstrated features of monocyte-macrophage lineage. Cytogenetic and polymerase chain reaction (PCR) analysis of the HSC-M1 cell line and involved bone marrow demonstrated the characteristic non-random chromosomal translocation t(2:5)(p23:q35). Reverse transcriptase PCR for mRNA expression of cytokines and cytokine receptors showed that HSC-M1 cells expressed the message for multiple cytokines and their receptors. Measurement of cytokine levels in serum samples using enzyme-linked immunosorbent assays showed increased concentrations of several cytokines. The increased levels of some cytokines correlated with disease activity and clinical symptoms. Although spontaneous production by HSC-M1 cells of some of these cytokines was demonstrated, the production of others was only detectable after stimulation with exogenous CD30 ligand. With few exceptions, there was good correlation between serum cytokine levels and cytokines produced by HSC-M1 cells. These findings indicate that cytokine production is a feature of ALCL cells and that some of the clinical manifestations in ALCL may result from cytokines produced by either the malignant or accessory cells.

Chromosomes, Human, Pair 2↗
PubMed2000

Comparative genomic hybridization analysis of clear cell sarcoma of the kidney.

BACKGROUND: Clear cell sarcoma of the kidney (CCSK) is a rare malignant pediatric tumor, distinguished from the Wilms tumor by its characteristic histologic features and a more aggressive clinical behavior with a tendency to metastasize to bone. Genetic studies on CCSK are limited and no consistent findings have been reported. PROCEDURE: We examined four cases of CCSK for presence of consistent genetic alterations using comparative genomic hybridization (CGH). This is the first report concerning CGH analysis of CCSK. RESULTS: Three of the tumors showed no chromosome gains or losses. One of the tumors had gains of 1 q and the terminal end of 11 q. CONCLUSIONS: These results are consistent with previous findings of limited chromosomal changes in CCSK karyotypes. Gain of 1 q in CCSK warrants further investigation. Copy number gains of 1 q have been repeatedly demonstrated in soft tissue and bone sarcomas, as well as other tumors, implying the presence of genes involved in tumor development and/or progression.

Child↗
PubMed2000

The effects of prebiopsy corticosteroid treatment on the diagnosis of mediastinal lymphoma.

BACKGROUND/PURPOSE: For children with probable mediastinal lymphoma and a high risk of cardiorespiratory morbidity, many centers recommend delaying the diagnostic biopsy for 24 to 48 hours while corticosteroids are administered to reduce tumor size and morbidity. This study was undertaken to determine the effect of preoperative steroid use on the accuracy of the pathological diagnosis and incidence of perioperative cardiorespiratory morbidity. METHODS: From 1988 to 1998, 86 children were treated for mediastinal lymphoma. Twenty-three received steroid before biopsy (study group) because of clinical evidence of respiratory compromise, and the remaining 63 served as controls. Clinical parameters, steroid use, and detailed pathological findings obtained at initial and subsequent biopsies were reviewed. Steroid treatment was considered to have had an adverse effect on the pathological diagnosis if (1) a definitive diagnosis was delayed more that 1 month, (2) a definitive diagnosis could not be made, or (3) the extent of disease could not be staged with certainty. RESULTS: Steroid treatment had an adverse effect on the pathological diagnosis in 5 of 23 (22%) children: 1 diagnostic delay, 3 failures of a definitive diagnosis, and 1 possible failure of staging. A definitive diagnosis was made in all control patients. Perioperative survival was 100% in both groups. At biopsy, only 3 children in the steroid treatment group and 2 children in the control group had moderate, nonfatal cardiorespiratory instability. Parameters of steroid use among children who had inaccurate pathological diagnoses or cardiorespiratory morbidity were not significantly different from those who did not. CONCLUSIONS: Steroid treatment before biopsy of mediastinal lymphoma may adversely affect the pathological accuracy or cause a delay in definitive diagnosis in a minority of cases. The dose and duration of steroid use was not related to outcome. Prebiopsy steroid appears to minimize the likelihood of cardiorespiratory morbidity in high-risk patients.

Adolescent↗
PubMed1999

Application of comparative genomic hybridization, spectral karyotyping, and microarray analysis in the identification of subtype-specific patterns of genomic changes in rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) in children occurs predominantly as two major histologically defined subtypes called embryonal RMS (RMS-E) and the prognostically less favorable alveolar RMS (RMS-A). Comparative genomic hybridization (CGH) was performed on 21 RMS and identified consistent gains affecting chromosomes 2 (8/10), 5 (5/10), 6 (3/10), 7 (7/10), 8 (9/10), 11 (6/ 10), and 12 (5/10) in RMS-E. Losses/deletions involved chromosomes 19 (2/10) and chromosomes 4, 9, 10, 17, 21 (1/10 each). High copy number amplification, involving the 2p24 region (5/11) and less frequently, the 12q13-21 (2/11), 9p22 (1/11), and 17q22-25 (1/11) regions, was detected in RMS-A. Gene amplification at band 2p24 was present in 6/12 alveolar tumors, and in each case, MYCN was amplified, together with the distally placed DDX1 gene. For these patients there was a shorter disease free interval and a higher mortality than patients with tumors without amplification. Detailed spectral karyotype analysis (SKY) was performed on two RMS cell lines (one of each subtype) and identified a surprisingly high level of structural change. Gene expression studies with the Atlas Human Cancer Array (588 genes) showed that 153 genes generated a signal of similar intensity in both cell lines, and 45 genes appeared to have subtype-specific expression. The chromosomal location of differentially expressed genes was compared to the pattern of genomic alteration in RMS as determined by CGH in this study and the literature.

Chromosome Aberrations↗
PubMed1999

Erosive adenomatosis of the nipple in an eight-year-old girl.

Erosive adenomatosis of the nipple (EAN) is a rare, benign neoplasm of breast lactiferous ducts. Peak incidence is in the fifth decade in women. Clinically, it may be mistaken for Paget's disease and, histologically, for adenocarcinoma. Some authors have proposed an association with breast carcinoma and fibrocystic breast changes. Erosive adenomatosis of the nipple is extremely rare in children. Treatment is usually local excision of the nipple. This is the first formal English language case report of EAN in the pediatric age group. It is important for dermatologists to be familiar with this entity to prevent unwarranted breast removal.

Adenocarcinoma↗
PubMed1999

Analysis of chromosome 22q as an aid to the diagnosis of rhabdoid tumor: a case report.

Malignant rhabdoid tumor is a highly aggressive tumor of childhood that may present as a soft-tissue primary tumor. We report a soft-tissue neoplasm that was polyphenotypic by immunohistochemical expression of epithelial, mesenchymal, and neural markers and did not meet the criteria for any of the usual pediatric small round-cell tumors. The findings raised the diagnosis of rhabdoid tumor, leading to testing for WT1 mRNA and protein expression, which were positive, as has been reported for renal rhabdoid tumor. This tumor had the typical clinical behavior of rhabdoid tumor with therapy resistance and early tumor-related death. Multicolor spectral karyotyping of this neoplasm showed a balanced translocation between chromosomes 1 and 22 with breakpoints at 1p36 and 22q11-12. The latter region is commonly involved in rhabdoid tumor. This change was also identified by fluorescence in situ hybridization. This case suggests that studies of chromosome 22 may be required to distinguish rhabdoid tumor from other soft-tissue tumors.

Chromosomes, Human, Pair 22↗
PubMed1998

Colo-colic intussusception associated with pneumatosis cystoides intestinalis.

This paper describes pneumatosis cystoides intestinalis in association with colo-colic intussusception in a young teenager. The intussusception was easily reduced at barium enema. The recognition of the characteristic filling defects in the barium column facilitates a correct diagnosis. This association has only been reported previously in six adults.

Adolescent↗
PubMed1998

Congenital thymic cysts in children--mostly misdiagnosed.

BACKGROUND/PURPOSE: Thymic cysts are rare lesions of the neck and mediastinum that are difficult to diagnose. Often considered inconsequential, these lesions can frequently be symptomatic. In this report the authors contrast their experience with that of the literature. METHODS: From 1984 through 1997, the authors encountered 14 patients with this lesion. All cysts were completely excised. Patients that had an acquired cyst of the thymus were excluded from this series. RESULTS: Of the 14 patients ranging in age from 2 weeks to 16 years, seven patients had cervical masses, five had mediastinal masses, and two children had both sites involved. Seven children were symptomatic with wheezing and upper respiratory infection, with cough and fever being the most common clinical features. Investigations included chest radiograph, contrast esophagram, sonography (US) and computerized tomography (CT). Displacement of vital mediastinal or neck structures was observed in eight patients. Only two patients received correct diagnosis before surgery. Successful and complete excision of all cysts was achieved. The cysts were benign and ranged in size from 2 to 22 cm in diameter. CONCLUSION: Often forgotten, thymic cysts are rare benign lesions that should be considered in the differential diagnosis of cervical and mediastinal masses in children.

Adolescent↗
PubMed1998

Cyclosporine in the treatment of an unusual case of juvenile systemic sclerosis.

We describe a child who initially presented with juvenile dermatomyositis (JDM). Four years after the complete remission of JDM she developed systemic sclerosis without internal organ involvement. She was unresponsive to a combination of systemic corticosteroid therapy and pencillamine. The institution of cyclosporine induced a complete remission.

Adolescent↗