Length of Telomeric Repeats in Neuroblastoma: Correlation with Prognosis and Other Biological Characteristics

Abstract

Telomeres are the physical ends of eukaryotic chromosomes. In view of reports of the reduction of telomeric repeats in human malignant tumors, we measured the lengths of telomeric repeats in 55 primary neuroblastomas. The average lengths of telomeric repeats in these tumors fell in a wide range (from 1.1 kb to more than 23 kb) relative to those in ganglioneuromas and normal peripheral mononuclear cells. The reduction of telomeric repeats was significantly correlated with advanced stages of tumor development, poor prognosis, and increased S‐phase fractions in tumor cells. On the other hand, three cases of Stage IV‐S tumors showed the reduction of telomeric repeats and low percentage of S‐phase fractions. These Stage IV‐S patients had a good prognosis with spontaneous regression of metastatic tumors.

Telomeres: Prognostic markers for solid tumors

“…Using multivariate Cox proportional hazards analysis, telomere length in this cohort was found to be a prognostic factor independent of tumor stage, with an overall relative risk for elongated telomeres of 6.48 (p 5 0.04). 19 It is noteworthy that these studies on telomere length and their association with prognosis in colorectal carcinoma patients showed the opposite relationship, with longer telomeres indicating poor prognosis, as compared to studies in other cancer types [13][14][15][16]21 One explanation for this discrepancy might lie in the differential regulation of telomerase expression in colorectal epithelial cells. In this context, normal colorectal epithelium has been shown to contain cells of possible stem cell origin that are telomerase-positive and presumably counteract telomere attrition due to physiologically high cell proliferation rates, and total cell loss due to physiological shedding in this specialized cell compartment.…”

“…42 Regardless of the methodology used, the following discussion shows that telomeres can be used as clinical biomarkers in the prognosis of solid tumors, as reported in numerous studies. [12][13][14][15][16][17][18][19][20][21][22][23][24] These studies, and their major findings, are summarized in Table I and further discussed here in detail, according to the type of solid tumors analyzed.…”

“…For these reasons, numerous investigators have hypothesized that altered telomere length could predispose cells to possess the properties necessary to metastasize and cause recurrent disease, and thereby be a predictor of clinical outcome. [12][13][14][15][16][17][18][19][20][21][22][23][24] This concept is shown schematically in Figure 1.…”

“…[8][9][10][11] This review summarizes the use of telomere length or its proxies, such as telomere content, as potential prognostic markers in solid tumors, a possibility that has been raised in the last decade by a number of investigators. [12][13][14][15][16][17][18][19][20][21][22][23][24] A corresponding comprehensive discussion of these promising developments has not yet been offered, in spite of the growing body of knowledge. Excluded from this discussion are numerous reports on the prognostic value of telomeres in hematological malignancies, a research area that, in contrast to solid tumors, has been addressed in more depth and previously reviewed.…”

Proliferation marker KI‐S5 discriminates between favorable and adverse prognosis in advanced stages of neuroblastoma with and without MYCN amplification

“…31 In a few cases, fluorescence in situ hybridization on paraffin embedded specimens was used. 32 Briefly, paraffin embedded tumor samples were cut as for immunohistochemistry.…”