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Biomedical subjects

H B Marsden

Publications and source records attributed to H B Marsden.

At least 37 records · Page 2Linked to original sources

Improvements in survival from childhood cancer: results of a population based survey over 30 years.

Survival from cancer of children whose cancer was diagnosed during the 30 years 1954-83 was analysed. The study was population based with nearly 3000 cases covering about 30 million child years at risk. When survival during the three decades 1954-63, 1964-73, and 1974-83 was compared striking improvements were observed. For all childhood cancer five year survival increased from 21% in the first decade to 49% in the third decade. During the first and third decades five year survival rates for acute lymphocytic leukaemia increased from 2% to 47%, Hodgkin's disease from 44% to 91%, non-Hodgkin's lymphoma from 18% to 45%, Wilms's tumour from 31% to 85%, and germ cell tumours from 10% to 64%. Twenty patients developed second primary tumours, but otherwise there were few late deaths. Less than 1% of children who survived without a relapse for 10 years subsequently died of their initial cancer. Survival from childhood cancer is no longer rare, and people who have been cured of cancer during childhood should be accepted as normal members of society.

Adolescent↗

Tamm-Horsfall protein is a marker of renal and extra-renal rhabdoid tumours.

A monoclonal antibody (MAb) to Tamm-Horsfall protein (THP) was used to stain 6 renal rhabdoid tumours (RRT) and 2 primary extra-renal rhabdoid tumours (E-RRT). One of the E-RRT was a tumour from the posterior fossa of a 3-year-old child and the other was a lump from the right side of the neck in an 18-month-old girl. Five of 6 RRT and both cases of E-RRT were positive for THP. Both cases of E-RRT also reacted with vimentin and cytokeratin MAbs. On electron microscopy, cells from both E-RRT were seen to contain concentric whorls of intermediate filaments characteristic of rhabdoid tumours. Viable tissues from one RRT and one E-RRT (the posterior fossa tumour) were available for tissue culture. Ninety-five percent of the cells growing out of both tumours were polygonal and approximately 5% of these cells were THP-positive.

Biomarkers, Tumor↗

Malignant disease in the mothers of children with Ewing's tumour.

Previous research has shown that mothers of children with soft tissue sarcoma, osteosarcoma, and chondrosarcoma are at excess risk of developing breast cancer. The occurrence of malignant disease in the mothers of a population-based series of children with Ewing's sarcoma was investigated in order to determine whether these mothers were at excess risk of cancer and of breast cancer in particular. Sixty-one mothers were traced; there were two cases of breast cancer and two other registrable neoplasms. Risk of malignancy in the mothers was not in excess of expectation.

Adult↗

Primary rhabdoid tumour of the brain.

A posterior fossa tumour in a 3 year old child is presented with characteristic histological, ultrastructural and immunohistochemical features of rhabdoid tumour. Many tumour cells contained cytoplasmic eosinophilic hyaline inclusions. Ultrastructurally concentric whorls of 10 nm intermediate filaments were identified. Immunohistochemical staining disclosed vimentin, cytokeratin and epithelial membrane antigen positivity. Renal and extrarenal rhabdoid tumours have been well documented but a primary rhabdoid tumour of the brain is extremely rare. Additional ultrastructural features seen were tubular crystalline inclusions in endoplasmic reticulum and abnormal large mitochondria.

Autopsy↗

Neurofibromatosis in children with soft tissue sarcoma.

Case records of the 157 children with soft tissue sarcoma in the Manchester Children's Tumour Registry diagnosed between 1954 and 1983 were reviewed for reference to diagnostic features of neurofibromatosis (NF). Interviews were carried out with 124 families of these children. Four children in the series were identified as having NF. All four were boys, very young at diagnosis, and had rhabdomyosarcomas of the bladder or prostate. In addition, there were indications that a further nine children may have been affected. It is suggested that NF may be more common in children with soft tissue sarcoma than previously thought and that clinicians should be alert for signs and symptoms of NF in such children and their families. Affected children may be at increased risk of developing further malignancies.

Adolescent↗

A classification scheme for childhood cancer.

The International Agency for Research on Cancer (IARC) is sponsoring a worldwide study of childhood cancer incidence. Cancers in children are highly specific and differ in many ways from cancers found in adults. Data for the international study will be presented according to the classification scheme described below which has been devised specifically for use with paediatric cancers. The features of this scheme are: (1) it is based on the International Classification of Diseases for Oncology (ICD-O); (2) diagnostic groups are defined mainly in terms of morphology; (3) the common types of childhood cancer are individually specified; (4) certain other rare conditions of interest are distinguished; (5) it provides for flexibility of data presentation with respect to amount of detail; (6) all possible combinations of ICD-O morphology and topography codes are included; and (7) the maximum number of codes has been allocated to specific categories. There is a great need for standardization in the classification of childhood cancers and we propose that the scheme be used for presentation of incidence data for results of aetiological and other related studies of cancer in children.

Child↗

A cell line from Wilms' tumour with deletion in short arm of chromosome II.

A cell line (T3/73) from a Wilms' tumour has been established from a 9 month-old boy with aniridia. The tumour was removed in 1973. On histological examination a diagnosis of Wilms' tumour was made which showed undifferentiated areas, marked tubule formation and abundant striped muscle fibres. The tumour cells, which are fusiform, grew rapidly in culture without the addition of growth factors, and have undergone over 100 passages. Approximately 95% and 5% were positive for desmin and cytokeratin, respectively. The cell doubling time was 28 hr. Cytogenetic studies revealed a karyotype of 46,XY,del(11) (p12::p14). Although the cells stained very intensely with a monoclonal antibody that detects oncogene ras p 21 antigen, Southern blot analysis using c-Ha-ras as a probe failed to reveal an obvious deletion or amplification of either Ha-ras allele.

Antibodies, Monoclonal↗

Patterns of multiple primary tumours in patients treated for cancer during childhood.

One hundred and sixty one children who have developed more than one primary neoplasm have been identified. Children with tumours of the central nervous system, retinoblastoma and leukaemia were those most frequently observed to develop a second malignancy whilst osteosarcoma was the most common second tumour. The patterns of second neoplasms appear to be changing and a recent increase in the number of children with leukaemia and lymphoma who develop second primary tumours has been observed. In this series, the two most frequent associations of tumours were retinoblastoma followed by osteosarcoma and the combination of acute leukaemia with a tumour of the central nervous system. Genetic factors which may have contributed to the development of the second primary tumour were identified in 53 patients (33%), 33 of whom had the genetic form of retinoblastoma. In an analysis of the treatment of 151 patients, for whom the interval between the two neoplasms was greater than 12 months, the second malignancy was considered to be 'radiation associated' in 93 (61%). Fifty children (33%) had been treated with either single or multiple agent chemotherapy which included an alkylating agent in 38. Forty five children had received a combination of chemotherapy and radiotherapy and of these, 10 developed leukaemia as their second tumour. Of the 19 secondary leukaemias, 16 have occurred in patients treated since 1970.

Adolescent↗

Evaluation of desmin as a diagnostic and prognostic marker of childhood rhabdomyosarcomas and embryonal sarcomas.

The diagnostic and prognostic relevance of desmin expression in 80 rhabdomyosarcomas (RMS) and 5 embryonal sarcomas (ES) was examined using a peroxidase anti-peroxidase staining procedure. Fifty-nine RMS but only one ES stained for desmin (P less than 0.05). The maximum percentage of desmin containing cells was 49 in RMS compared with only 1% in ES. Desmin positivity correlated inversely with survival (P less than 0.02) in that RMS with high proportions of desmin positive cells were associated with poorer prognoses than those containing fewer desmin positive cells. If the degree of expression of desmin is related to myogenic differentiation, then our results indicate that poorly differentiated RMS tend to have a better prognosis than the well differentiated tumours. One possible explanation is that the poorly differentiated RMS respond better to chemotherapy than to well differentiated RMS. A multivariant analysis incorporating desmin staining, treatment, histology, age and gender revealed that the two most significant independent prognostic factors were treatment and histology.

Desmin↗

Adrenal cortical tumours: epidemiological and familial aspects.

Epidemiological data on the 14 cases of adrenal cortical tumour registered with the Manchester Children's Tumour Registry from 1954 and 1985 are presented. The incidence of adrenal cortical carcinomas was 0.3%, mainly in girls, most of whom presented with virilisation. The incidence of neoplastic disease among close relatives was ascertained, but, except in siblings, this was not significantly higher than would be expected. Evidence from extended pedigrees, however, indicates that at least four of the children could be members of families with the SBLA (sarcoma, breast and brain tumour, leukaemia, laryngeal and lung cancer, and adrenal cortical carcinoma) cancer family syndrome, and that other relatives may be at risk of developing such neoplasms.

Adolescent↗

Study of childhood renal tumours using a monoclonal antibody to Tamm-Horsfall protein.

A monoclonal antibody to Tamm-Horsfall glycoprotein was used for the immuno-localization of Tamm-Horsfall protein in formalin fixed, paraffin embedded tissue sections of childhood renal tumours, normal children's kidneys, and human fetal kidneys. The procedure was a dinitrophenyl hapten sandwich staining method. The antibody, diluted 1/100,000, gave a very strong and specific staining of the loop of Henle and distal tubules of normal and fetal kidneys. No staining was seen in Wilms' tumour, mesoblastic nephroma, and bone metastasizing renal tumour of childhood. In contrast, two of seven renal carcinomas and three of four rhabdoid renal tumours were positive for Tamm-Horsfall protein.

Antibodies, Monoclonal↗

Malignant melanoma in families of children with osteosarcoma, chondrosarcoma, and adrenal cortical carcinoma.

Seven cases of malignant melanoma in the close relatives of children with osteosarcoma and chondrosarcoma are described. The association between certain childhood malignancies (adrenal cortical carcinoma, osteosarcoma, chondrosarcoma, retinoblastoma) and malignant melanoma is discussed and it is proposed that in certain families malignant melanoma may be another manifestation of the same gene defect which results in susceptibility to tumours characteristic of the SBLA cancer family syndrome.

Adolescent↗

Breast cancer risk in mothers of children with osteosarcoma and chondrosarcoma.

Mothers of a population-based series of 86 children with osteosarcoma or chondrosarcoma were traced and their health status or cause of death ascertained. There were 6 cases of breast cancer among these mothers and 6 other cancers. Risk of breast cancer was approximately three times that expected, and appeared to be highest in mothers of boys and in mothers of children under the median age at diagnosis. The mothers who developed breast cancer were relatively young at diagnosis compared with population data. Risk of other malignancies in the mothers was not in excess of expectation. These findings are in line with those reported for breast cancer risk in mothers of children with soft tissue sarcomas, and provide further indications of a genetic component in the aetiology of these cancers.

Adolescent↗

Gangliorhabdomyosarcoma: a histopathological and immunohistochemical study of three cases.

A histopathological and immunoperoxidase study on three cases of genitourinary gangliorhabdomyosarcoma using a spectrum of conventional staining methods and antibodies against myoglobin, neuron-specific enolase and S-100 protein is presented. The results of the study have shown that differentiated myoblasts, ganglion cells and Schwann cells reacted positively with the particular antisera, but the majority of undifferentiated cells were negative. From the immunopathology results it was not possible to determine whether the undifferentiated cells were precursors of neural cells or myoblasts; the histological appearance resembled that of mesenchymal cells commonly seen in rhabdomyosarcomas. Theories concerning the origin of these tumours from neural crest ectomesenchyme or from neural crest and somitic mesenchyme are considered. Further study is needed to establish their histogenesis.

Cell Nucleus↗

Study of childhood renal tumours using antisera to fibronectin, laminin, and epithelial membrane antigen.

Using a peroxidase-antiperoxidase staining procedure, formalin fixed paraffin embedded sections of fetal and normal kidney; benign (mesoblastic nephroma); and malignant tumours (Wilms' tumour, clear cell renal carcinoma, rhabdoid renal tumour, and bone metastasising renal tumour of childhood (BMRTC] were examined for their reactivity with antisera to fibronectin, laminin, and epithelial membrane antigen. Mesoblastic nephroma contained fibronectin but no laminin. Most Wilms' tumours lacked both fibronectin and laminin; 50% of rhabdoid renal tumours were positive for fibronectin and laminin--rhabdoid tumours as recognised morphologically may, in fact, be two separate entities. BMRTC and clear cell renal carcinoma lacked both fibronectin and laminin. Epithelial membrane antigen was present in most of the tubular Wilms' tumour but absent in blastemal Wilms' tumours. The presence of epithelial membrane antigen in rhabdoid tumours was surprising, as histologically, this type of tumour shows no sign of epithelial differentiation. Epithelial membrane antigen antiserum stained clear cell renal carcinomas: epithelial membrane antigen is found in the distal and not the proximal tubules of fetal and normal kidneys. Thus an obvious interpretation is that clear cell renal carcinomas originate from distal rather than from proximal tubules, as has always been thought. On the basis of these results and data from other published findings some possible histogenetic origins of childhood renal tumours were proposed.

Adenocarcinoma↗

New look at mesoblastic nephroma.

Thirty eight mesoblastic nephromas were studied. The age range of the patients was between the neonatal period and 18 months. The presence of cartilage is consistent with a mesoblastic origin, but squamous epithelium was a feature in three tumours. Particular attention was given to the adjacent renal tissue in which various histological features were noted: vacuolated and dysplastic tubules; cysts; and subcapsular epithelial tumourlets. The findings had aspects in common with both dysplastic kidneys and nephroblastoma. Classification of the tumours as normocellular and hypercellular was attempted, but there was considerable overlap. The behaviour of the tumour was good in all cases, although follow up was relatively short on some patients, and deaths from non-neoplastic causes occurred.

Cartilage↗

Study of childhood renal tumours using peroxidase conjugated lectins.

Six peroxidase conjugated lectins were used to compare their ability to bind to formalin fixed paraffin embedded tissue sections of childhood renal tumours (Wilms' tumour, mesoblastic nephroma, renal carcinoma, rhabdoid renal tumour, and bone metastasising renal tumour of childhood (BMRTC) with fetal and normal children's kidney. Lectins were found to be helpful in the differential diagnosis of renal tumours. Another important finding was that the mesenchyme of renal tumours showed differences in its reactivity among various types of kidney tumours. The results of lectin binding were not helpful in establishing the origin of kidney tumours.

Child↗