Monoclonal Antibody NB84 in the Differential Diagnosis of Neuroblastoma and Other Small Round Cell Tumors

Abstract

Two hundred fifty-five well-characterized formaldehyde-fixed and paraffin-embedded small round cell tumors mainly from children and young adults including 105 neuroblastomas were immunohistochemically analyzed with the NB84 monoclonal antibody raised to neuroblastoma cells. Most of the undifferentiated neuroblastomas (21 of 22) and all 83 differentiated neuroblastomas reacted with NB84, but none of these tumors were CD99 positive. Compared with synaptophysin, NB84 was more sensitive, although less specific, in the identification of neuroblastoma in formaldehyde-fixed tissue. In addition to neuroblastoma, skeletal and extraskeletal Ewing's sarcoma and medulloblastoma showed NB84 reactivity in approximately 20% of cases, and 50% of desmoplastic small round cell tumors showed positive cells, usually in smaller numbers than the neuroblastomas. The NB84 reactivity was seen slightly more commonly in morphologically defined (rosette-positive) cases of peripheral primitive neuroectodermal tumors than in Ewing's sarcoma. However, the NB84 positivity did not correlate with the expression of other neural markers (neurofilament proteins, CD57, and synaptophysin) in these tumors. All other small round cell tumors including rhabdomyosarcomas, Wilms' tumors, and lymphomas were NB84 negative. In the case of NB84-positive tumors other than neuroblastoma, their specific reactivity for other markers was useful (Ewing's sarcoma CD99 positive, desmoplastic small round cell tumor desmin and keratin positive). The NB84 monoclonal antibody is a useful reagent to separate neuroblastoma from other small round cell tumors. In problem cases it is best used in a panel together with other markers that address the significant differential diagnostic alternatives.

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

“…Compared to NB84, we found that synaptophysin, a neuroendocrine marker of well differentiated cells, was positive in 100% of the cases and highly expressed by tumors without potential for recurrence, making synaptophysin a potential marker to predict tumor behavior. Similar findings were also observed by Miettinen 7 and Bozzi. 30 For clinical and pathological use, it would be desirable that the aforementioned adjuvant methods could also provide information related to tumor prognosis, in addition to being easy to perform as well as rapidly assessable and reproducible.…”

“…Immunohistochemistry has proved to be a useful adjunctive method for the differential diagnosis of these tumors. 7,8,23 This is particularly true for the identification of lymphomas and leukemia, which are the most frequent members of this group of tumors. However, the diagnosis of neuroblastomas is more complex.…”

“…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.…”

Oct-4+/Tenascin C+ neuroblastoma cells serve as progenitors of tumor-derived endothelial cells

“…Oct-4 + cells were detected in all samples (Table 1). Next, these aspirates were double stained with anti-Oct-4 and anti-NB84 (an NB-specific marker) mAbs [40,41]. All BM Oct-4 + cells co-expressed NB84 (range 0.2-1.5%), thus proving their tumor origin (Table 1 and Figure 1B).…”

“…At variance with TEC, bulk tumor cells did not express PSMA, vWF, CD105, HLA-class I or HLA-G ( Figure 6A). Most TECs were found to express the NB-associated markers GD2 [49] NB84 [41], and CD56 [50] ( Figure 6B, 6-8), which were shared by most tumor cells ( Figure 6A). …”