Flow cytometric analysis of DNA content in children with neuroblastoma

Brenner, David; Barranco, S. C.; Winslow, Boyd H.; Shaeffer, James

doi:10.1016/s0022-3468(89)80250-7

Cited by 18 publications

(6 citation statements)

References 10 publications

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“…In 1988, Takeuchi [17] found that neither the DNA ploidy nor the proliferative index of neuroblastoma cells correlated with any of the conventional prognostic variables of neuroblastoma, whereas higher proliferative indices of neuroblastoma cells were associated with an unfavorable clinical outcome, though no correlation between the DNA ploidy of neuroblastoma cells and the survival of patients was evident. In 1989, Brenner et al [11] reported that the distribution of aneuploid and diploid cases above and under 1 year of age showed no statistically signi® cant difference, which supported our data. There are also studies [11,24] in which the pattern of distribution of the aneuploid and the diploid tumors in the favorable and the unfavorable stages had no statistically signi® cant difference.…”

Section: Discussionsupporting

confidence: 89%

“…In 1989, Brenner et al [11] reported that the distribution of aneuploid and diploid cases above and under 1 year of age showed no statistically signi® cant difference, which supported our data. There are also studies [11,24] in which the pattern of distribution of the aneuploid and the diploid tumors in the favorable and the unfavorable stages had no statistically signi® cant difference. All 6 aneuploid cases in our study had their primary tumor in the abdomen.…”

Section: Discussionsupporting

confidence: 89%

“…It is obvious that, when compared with fresh material, studies with paraf® n blocks have some drawbacks affecting the precision of¯ow cytometric studies. The method of Hedley et al [18] used in this study was found to be a reliable method for DNA content analysis in other studies [10,11,15]. The median age (36 months) in this series was higher when compared with that of POG series (22 months) [1].…”

Section: Discussionmentioning

confidence: 61%

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Dna Content and Proliferative Activity in Children With Neuroblastoma

Yalçın¹,

Kutluk²,

Kansu³

et al. 2000

Pediatric Hematology and Oncology

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Many studies have reported that neuroblastoma patients with aneuploid DNA content and a low cellular proliferative activity have better outcome; other studies have reported contradictory results. Formalin-fixed, paraffin-embedded archival pretreatment specimens of 56 neuroblastomas were studied. Thick sections from paraffin blocks were deparaffinized, and rehydrated. Following enzymatic digestion and filtration, cellular suspensions were analyzed by flow cytometry. Six tumors were aneuploid (13.3%) and 39 samples were diploid (86.7%). S-phase fraction (SPF) ranged from 1 to 78% with a median of 31%. DNA ploidy and proliferative activity results showed no correlation with the prognostic variables. There was no significant difference between the 5-year overall and event-free survival rates of the aneuploid and the diploid neuroblastomas or between the neuroblastomas with a high and low proliferative activity. The results revealed the prognostic significance of neither DNA ploidy nor the cellular proliferative activity in neuroblastoma in contrast to other studies.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 61%

See 1 more Smart Citation

Dna Content and Proliferative Activity in Children With Neuroblastoma

Yalçın¹,

Kutluk²,

Kansu³

et al. 2000

Pediatric Hematology and Oncology

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“…Subsequently, Brenner et al 4 and Gansler et alp reported a favorable outlook for neuroblastoma patients with aneuploid tumors. Ensley et al 21 reported that diploid, squamous cell carcinomas of the head and neck might be more resistant to capsulation-based chemotherapy than aneuploid tumors.…”

Section: Discussionmentioning

confidence: 99%

Potent effects of adjuvant chemotherapy using 5-fluorouracil + leucovorin on DNA aneuploid colorectal cancer

1998

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Background:The relationship between DNA ploidy of colorectal cancer cells and sensitivity to adjuvant chemotherapy, using 5-fluorouracil + leucovorin, was investigated.Methods: Seventy-five patients with Dukes' B or C colorectal cancer, who underwent potentially curative resection, were randomly allocated to 2 groups. Thirty-eight patients received adjuvant chemotherapy using 5-fluorouracil + leucovorin (chemotherapy group), and 37 patients received no adjuvant chemotherapies (no-chemotherapy group). Tumor cell ploidy of all patients was analyzed using paraffin-embedded samples.Results: There was no statistically significant difference in overall survival between patients who received chemotherapy and those who did not. Among the patients with diploid tumors (n = 39), there was no significant difference in survival between the chemotherapy group (n = 20, 5-year survival rate of 34.3%) and the no-chemotherapy group (n = 19, 5-year survival rate of 27.1%). By contrast, among the patients with aneuploid tumors (n = 36), the survival rate was significantly better in the chemotherapy group (n = 18, 5-year survival rate of 77.8%), than in the no-chemotherapy group (n = 18, 5-year survival rate of 43.7%) (P = 0.023). Conclusion:These results suggest that aneuploid tumors are more sensitive to adjuvant chemotherapy, using 5-fluorouracil + leucovorin, than are diploid tumors.

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“…DNA content was also shown to correlate with response to treatment: 17 of 17 hyperdiploid tumours had complete or partial responses, whereas 0 of 6 diploid tumours responded to treatment. Several subsequent flow cytometric studies [6][7][8][9][10][11] have confirmed and extended these findings, namely: that a hyperdiploid DNA content of tumour cells characterises low stage disease in younger patients with a favourable clinical course, whereas a normal cellular DNA content is associated with unfavourable clinical features and significantly reduced survival probability.…”

mentioning

confidence: 83%

Neuroblastoma tumour genetics: clinical and biological aspects

Bown¹

2001

Journal of Clinical Pathology

114

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Neuroblastoma tumour cells show complex combinations of acquired genetic aberrations, including ploidy changes, deletions of chromosome arms 1p and 11q, amplification of the MYCN oncogene, and-most frequently-gains of chromosome arm 17q. Despite intensive investigation, the fundamental role of these features in neuroblastoma initiation and progression remains to be understood. Nonetheless, great progress has been made in relating tumour genetic abnormalities to tumour behaviour and to clinical outcome; indeed, neuroblastoma provides a paradigm for the clinical importance of tumour genetic abnormalities. Knowledge of MYCN status is increasingly being used in treatment decisions for individual children, and the clinical value of 1p and 17q data as adjuncts or refinements in risk stratification is under active investigation. Reliable detection of these molecular cytogenetic features should be regarded as mandatory for all new cases at presentation. (J Clin Pathol 2001;54:897-910) Keywords: neuroblastoma genetics; 17q gain in neuroblastoma; neuroblastoma: 1p and MYCN; tumour genetics and prognosis Neuroblastoma is an embryonal tumour of neuroectodermal cells derived from the neural crest and destined for the adrenal medulla and sympathetic nervous system. The disease accounts for approximately 6% of childhood cancers, with an annual incidence of 8/million children under the age of 15. The median age at diagnosis is 22 months, and more than 95% of cases present by 10 years of age.1 There are approximately 90 new cases each year in the UK.The clinical hallmark of neuroblastoma is its variability. In children over the age of 1 year, approximately 75% of cases present with disseminated metastases (stage 4); these tumours are aggressive, chemoresistant, and generally incurable. It is principally the dismal outlook for this group of patients that accounts for the disproportionate contribution of neuroblastoma to childhood cancer mortality (approximately 15% of cancer related deaths).In contrast, infants with neuroblastoma tend to present with lower stage disease (stages 1, 2, and 4s), and the clinical behaviour of these tumours diVers greatly from the aggressive forms; they are generally chemosensitive and high cure rates are obtained. Moreover, a proportion of lower stage tumours show spontaneous regression, even those showing widespread dissemination in stage 4s disease. This extreme clinical heterogeneity has led some workers to question whether neuroblastoma may consist of two distinctly diVerent diseases.Hence, the well established clinical indicators of adverse prognosis are age > 1 year at diagnosis and advanced tumour stage.2 Clinical risk systems based on tumour histologydegree of ganglionic diVerentiation, extent of Schwannian stroma, etc-have also been developed. 4The biological hallmark of neuroblastoma is the complexity of the genetic abnormalities acquired by the tumour cells, and some of these abnormalities are powerful prognostic markers independent of the clinical features. This fact helps in r...

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Flow cytometric analysis of DNA content in children with neuroblastoma

Cited by 18 publications

References 10 publications

Dna Content and Proliferative Activity in Children With Neuroblastoma

Dna Content and Proliferative Activity in Children With Neuroblastoma

Potent effects of adjuvant chemotherapy using 5-fluorouracil + leucovorin on DNA aneuploid colorectal cancer

Neuroblastoma tumour genetics: clinical and biological aspects

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