Immunoexpression of cell cycle biomarkers in neuroblastoma samples and its correlation with prognostic factors

Noronha, Lúcia de; Araújo, Deli Grace de Barros; Gozzo, Priscilla do Carmo; Harada, Luana E.; Percicote, Ana Paula; Nagashima, Seigo; Gugelmin, Elisabeth Schneider; Watanabe, Flora; Machota, Milton Marcio; Cunha, Isabela Werneck da

doi:10.1590/s1676-24442013000100009

Cited by 2 publications

(1 citation statement)

References 37 publications

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“…13,[16][17][18][19] The MIB-1 index has been found to be significantly lower in cases of Schwannian-stroma-rich neuroblastomas and significantly higher in poorly differentiated cases. 14 MIB-1 index values are generally similar in studies performing manual counts [13][14][15][16][17][18] and the surprisingly few that have used image analysis. 19 Reported values range from 0% to 82%, which are virtually identical to our results of 0% to 81.8%.…”

Section: Discussionmentioning

confidence: 86%

MIB-1 Index as a Surrogate for Mitosis-Karyorrhexis Index in Neuroblastoma

Atikankul¹,

Atikankul

Santisukwongchote³

et al. 2015

American Journal of Surgical Pathology

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Neuroblastoma, the most common extracranial solid tumor in infancy, shows marked biological heterogeneity. Multiple prognostic markers are combined to risk-stratify neuroblastoma patients for treatment. One marker assesses histology, dividing patients into favorable and unfavorable categories based, in part, on the mitosis-karyorrhexis index (MKI). The recommended scoring of 5000 cells is, however, time-consuming and observer-dependent, and accurate counts may not always be performed. In the present study, we investigated using MIB-1 as a surrogate marker for the MKI. Twenty-five cases of neuroblastoma, ranging from low to high MKI, were immunostained for MIB-1. A total of 375 microscopic fields were digitally captured with > 100,000 cells scored. The MIB-1 index was determined by image analysis and MKI, by manual counting of the same immunostained fields. There was a significant correlation between the MIB-1 index and MKI comparing all fields (r = 0.7869, P < 0.01) and an even better correlation comparing individual cases (r = 0.9147, P < 0.01). Using a linear regression model, a formula was generated to calculate MKI from the MIB-1 index as follows: MKI = (MIB-1 index × 0.124) + 1.412. With this formula, a low MKI corresponds to an MIB-1 index < 4.74, intermediate MKI to an MIB-1 index of 4.74 to 20.87, and high MKI to an MIB-1 index > 20.87. For comparison, the calculations were repeated using a manual MIB-1 count on the same images. Similar significant correlations were obtained, with nearly identical cutoff values for MKI categories. This approach can facilitate determination of the MKI by assessing the MIB-1 index, either by image analysis or manual counting.

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Section: Discussionmentioning

confidence: 86%

MIB-1 Index as a Surrogate for Mitosis-Karyorrhexis Index in Neuroblastoma

Atikankul¹,

Atikankul

Santisukwongchote³

et al. 2015

American Journal of Surgical Pathology

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Expression level of quiescin sulfhydryl oxidase 1 (QSOX1) in neuroblastomas

et al. 2014

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Neuroblastoma is the most common extracranial solid malignant tumor observed during childhood. Although these tumors can sometimes regress spontaneously or respond well to treatment in infants, genetic alterations that influence apoptosis can, in some cases, confer resistance to chemotherapy or result in relapses and adversely affect prognosis for these patients. The aim of this study was to correlate immunohistochemical expression of the protein quiescin sulfhydryl oxidase 1 (QSOX1) in samples obtained from untreated neuroblastomas with the patients’ clinical and pathological prognostic factors and clinical course. Neuroblastoma samples (n=23) obtained from histology blocks were arrayed into tissue microarrays and analysed by immunohistochemistry. The cases were classified according to the following clinical and pathological prognostic factors: age at diagnosis greater or less than/equal to 18 months; location of the lesion at diagnosis (abdominal or extra-abdominal); presence or absence of bone-marrow infiltration; tumor differentiation (well or poorly differentiated); Shimada histopathologic classification (favourable or unfavourable); state of the tumor extracellular matrix (Schwannian-stroma rich or poor); amplification of the MYCN oncogene; and clinical course (dead or alive with or without relapses/residual lesions). Twelve of the cases were female, 9 children were over 18 months old, 9 cases presented with extra-abdominal tumors and 9 cases exhibited tumors with unfavourable histologies. Fifteen patients underwent bone-marrow biopsy, and 4 of these were positive for metastasis. Nine patients died. The higher immunohistochemical expression of QSOX1 was more common in well-differentiated samples (P=0.029), in stroma-rich samples (P=0.029) and in samples from patients with a high prevalence of relapses/residual disease. The functions of QSOX1 include extracellular matrix maturation and the induction of apoptosis. Therefore, QSOX1 may be involved in neuroblastoma differentiation and regression and may thus function as a biomarker for identifying risk groups for this neoplasm.

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Immunoexpression of cell cycle biomarkers in neuroblastoma samples and its correlation with prognostic factors

Cited by 2 publications

References 37 publications

MIB-1 Index as a Surrogate for Mitosis-Karyorrhexis Index in Neuroblastoma

MIB-1 Index as a Surrogate for Mitosis-Karyorrhexis Index in Neuroblastoma

Expression level of quiescin sulfhydryl oxidase 1 (QSOX1) in neuroblastomas

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