Proliferation and apoptosis in neuroblastoma: subdividing the mitosis-karyorrhexis index

The Shimada classification is a frequently used, histopathological classification system for neuroblastoma tumours. Tumours are classified as prognostically favourable or unfavourable based upon stroma content, degree of neuroblastic maturation and patient age at diagnosis. The mitosis-karyorrhexis index is introduced in this classification system, as the cellular density sum of mitotic and karyorrhectic cells in the tumour. The biological nature of karyorrhectic cells is uncertain, but a high mitosis-karyorrhexis index in stroma-poor tumours is an indicator of poor prognosis. In this study, neuroblastoma tumours were analysed for cell proliferation, using antiproliferating cell nuclear antigen (PCNA) immunohistochemistry, and apoptosis, by morphology and in situ end-labelling of fragmented DNA. The karyorrhectic cells described in the Shimada classification were shown to be either proliferating or undergoing apoptosis. It is further shown that a high cellular density of proliferating cells correlates with poor prognosis, whereas a high density of apoptosis, in contrast, indicates favourable outcome.