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1.
Acta Neurochir (Wien) ; 160(4): 793-800, 2018 04.
Article in English | MEDLINE | ID: mdl-29188366

ABSTRACT

INTRODUCTION: The neutrophil-lymphocyte count ratio (NLCR) is an established prognostic marker for renal, lung and colorectal carcinomas and has been suggested to be predictive of histological grade and outcome in adult intracranial tumours. The purpose of this study was to determine whether a correlation of the pre-operative neutrophil count (NC) and NLCR with the final histological grade exists in paediatric intracranial tumours. METHODS: A retrospective analysis was undertaken at a single centre. Patients less than 18 years old at the time of surgery who underwent tumour-related procedures from 2006 to 2015 were included. Patients with recurrent tumours, previous bone marrow transplant and metastases were excluded. Pre-operative full blood counts (FBC), collected before the diagnosis of intracranial pathology and before administration of steroids, were matched with histological diagnosis for each patient. Post-operative FBC was also recorded, together with survival data where applicable. RESULTS: A total of 116 patients (74 male, 42 female; mean age, 8 ± 0.9 years) with a diagnosis of primary intracranial tumours had pre-operative FBC that could be matched to final histological grade. Pre-operative NC and NLCR were higher with increasing grade of tumour: grade 1 (NC 4.29 109/l, NLCR 2.26), grade 2 (NC 4.59 109/l, NLCR 2.38), grade 3 (NC 5.67 109/l, NLCR 2.72) and grade 4 (NC 6.59 109/l, NLCR 3.31). Patients with WHO grade 1 and 2 tumours pooled together had a lower NC (4.37 95% CI ± 0.67 109/l) compared to WHO grade 3 and 4 patients (6.41 95% CI ± 0.99 109/l, p = 0.0013). The NLCR was lower in grade 1 and 2 tumours (2.29 ± 0.59) (compared to grade 3 and 4 tumours; 3.20 ± 0.76) but this did not reach significance (p = 0.069). The subgroup of patients with pilocytic astrocytoma had a significantly lower NC when compared to patients with high-grade tumours (p = 0.005). Medulloblastoma and supratentorial PNET subgroups had significantly higher NC compared to the low-grade group (p = 0.033, p = 0.002). Post-operative NC was significantly higher in the high-grade tumours (p = 0.034), but no difference was observed for NLCR (p = 0.28). CONCLUSIONS: No evidence exists to support the correlation of pre-operative NC or NLCR to histological diagnosis in paediatric intracranial tumours. Our results indicate that a higher pre-operative NC/NLCR correlates with a higher histological grade of tumour. This suggests that immunological mechanisms may be involved in the pathogenesis of paediatric brain tumours, and a further prospective study is required to substantiate and expand these findings.


Subject(s)
Astrocytoma/blood , Brain Neoplasms/blood , Cerebellar Neoplasms/blood , Medulloblastoma/blood , Neoplasm Recurrence, Local/blood , Adolescent , Astrocytoma/epidemiology , Astrocytoma/pathology , Brain Neoplasms/epidemiology , Brain Neoplasms/pathology , Cerebellar Neoplasms/epidemiology , Cerebellar Neoplasms/pathology , Child , Child, Preschool , Female , Humans , Leukocyte Count , Male , Medulloblastoma/epidemiology , Medulloblastoma/pathology , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/pathology
3.
J Med Genet ; 47(11): 771-4, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20805372

ABSTRACT

INTRODUCTION: The Li-Fraumeni Syndrome is caused by a germline TP53 mutation and is associated with a high risk of breast cancer at young ages. Basal (triple negative) breast cancers are now well recognised to be a typical sub-type of breast cancer developing in a large proportion of BRCA1 gene carriers. We considered whether a similar narrow sub-type of breast cancer was found in TP53 gene mutation carriers. OBJECTIVE: A hypothesis generating study to investigate whether there are specific breast tumour characteristics associated with germline TP53 mutations. METHODS: Pathological characteristics in 12 breast cancers arising in nine patients carrying pathogenic TP53 mutations were compared to a reference panel of 231 young onset breast tumours included in the POSH study. RESULTS: Patients carrying a TP53 mutation showed a significantly higher likelihood of developing a breast cancer with Human Epidermal growth factor Receptor (HER2) amplification (83%) when compared to the cohort of young onset breast cancer cases (16%); ER and PR status were equivalent between groups. CONCLUSION: These findings suggest that breast cancer developing on a background of an inherited TP53 mutation is highly likely to present with amplification of HER2.


Subject(s)
Breast Neoplasms/genetics , Germ-Line Mutation , Receptor, ErbB-2/genetics , Tumor Suppressor Protein p53/genetics , Adult , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , DNA Mutational Analysis , Female , Gene Amplification , Humans , Immunohistochemistry , In Situ Hybridization , Li-Fraumeni Syndrome/genetics , Receptor, ErbB-2/metabolism , Tumor Suppressor Protein p53/metabolism , Young Adult
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