Flow cytometric DNA analysis of neuroblastoma. Correlation with histology and clinical outcome

Abstract

Clinical and histologic features of 38 cases of neuroblastoma were compared with data obtained by flow cytometric DNA analysis. Favorable clinical outcome was associated with an aneuploid stem line (P < 0.01) and a low percentage of tumor cells in the S, G I , and M phases of the cell cycle (P < 0.005).These favorable cytometric features were also associated with a favorable clinical stage (1, 2, 4s), and histologic evidence of Schwann's cell and ganglion cell differentiation. Consideration of cytometric data improved the sensitivity, specificity, and predictive efficiency of a current system for histologic grading of neuroblastoma.Cancer 58:2453-2458, 1986. HE PROGNOSIS OF CHILDREN WITH TUMORS Of theT sympathetic nervous system has been shown to correlate highly with several clinical, biochemical, and histologic Shimada et al. have recently shown that three morphologic features are particularly useful in predicting the behavior of these tumors: (1) the proportion of neuroblastic and Schwann's cells; (2) the extent of ganglion cell differentiation; and (3) the percentage of mitotic figures and karyorrhectic nuclei (mitotic karyorrhectic index, MKI). Flow cytometric DNA analysis (FCDA), like the MKI, provides information concerning growth lunetics. FCDA is also used to detect abnormal tumor DNA content (aneuploidy), which has been associated with a favorable outcome in cases of neur~blastoma.~ Previous studies from this and other laboratories have also demonstrated the usefulness of FCDA in the diagnosis of neoplastic and preneoplastic disorders of the uterine cervix, bladder, lung, breast, gastrointestinal tract, and other site^.^,^ In order to evaluate the prognostic value of FCDA of neuroblastoma and ganglioneuroblastoma, a retrospective study of 38 cases was undertaken. The percentage of cells in the S and G2/M phase ofthe cell cycle (%SG*M) showed a highly significant association with clinical outcome, and when incorporated into the histologic classi-

Morphometric Evaluation of Nb84, Synaptophysin and Agnor Is Useful for the Histological Diagnosis and Prognosis in Peripheral Neuroblastic Tumors (Pnts)

“…Regardless of the mechanism, the quantification of collagen can also provide prognostic information in pNTs. Other classic markers investigated in our study were Ki-67, 17 p53 15,18 and DNA ploidy, 13,14,23 which did not show association with NTs prognosis.…”

“…Because the monoclonal antibody NB84 directed to an unknown molecule of 57 kDa can provide considerable assistance in the recognition of the neuroblastic differentiation, NB84 has been thought to be important as an adjuvant to the diagnosis in the routinely processed specimens. [7][8][9] In addition, as the nuclear and stromal activity of tumor cells have been shown to influence tumor invasion and metastases, specific markers such as AgNOR, [10][11][12] DNA ploidy, [13][14][15] Ki-67, 16,17 p53, 15,16,18 collagen and neuropil matrix components have also been targeted as potential useful tumor markers. 16,[19][20][21][22] To validate the importance of NB84, synaptophysin and AgNOR and to explore the quantitative relationship between these factors and histological diagnosis and prognosis, as well as the relationship between NB84, synaptophysin and AgNOR and other tumor and stromal factors, we studied these markers in peripheral neuroblastic tumors and herein report our results.…”

Nuclear DNA content and morphological characteristics in the prognosis of adrenocortical carcinoma

“…An association of DNA diploidy with shorter survival has been previously reported in neuroblastoma (Look et al, 1984;Gansler et al, 1986;Oppedal et al, 1988;Abramowsky et al, 1989). A cytogenetic study of neuroblastomas showed that the karyotype of the majority of aneuploid tumours consisted of three nearly complete haploid sets of chromosomes, in contrast to that of diploid tumours, which were characterised by extensive structural chromosomal aberrations (Kaneko et al, 1987).…”

Multifocal neuroblastoma

“…51,52 Molecular analyses of neuroblastoma have also revealed several prognosis-associated biologic characteristics of tumor cells. Amplification of the MYCN gene 18,30,53 is the most famous indicator of an unfavorable tumor, whereas NTRK1 expression, 19 Haras p21 expression, 54 and a DNA near-triploid pattern 21,55,56 are frequently detected in favorable tumors. In the current study, no tumors exhibited MYCN amplification, whereas all tumors showed NTRK1 and Ha-ras p21 expression.…”