Prognostic significance of nucleolar organizer regions (NORS) in malignant melanoma

Abstract

Nucleolar organizer regions (NORs) are loops of ribosomal DNA (rDNA) in the nucleolus and are associated with acidic proteins. They are seen in routinely processed paraffin sections by using a one‐step colloidal silver (Ag) staining method; they appear as black dots termed “AgNORs”. The quantitative assay of AgNORs has been used to differentiate benign from malignant neoplasms. Melanocytic lesions differ significantly in AgNOR counts between malignant melanoma and nevi. However, conflicting results have been reported as to AgNORs' prognostic value in melanoma. A recent study showed AgNOR counts to be a more accurate prognostic indicator than Breslow's thickness. In this study, we counted the AgNORs in 26 patients with primary cutaneous melanomas (CMM) between 2.0 mm and 2.5 mm thick. Of these, 14 are alive without disease (AN) at 5 years after diagnosis (group 1), and 12 are dead of disease (DD) in less than 5 years (group 2). The AgNORs were scored in 30 nuclei per tumor, and the means were calculated. For group 1, the mean number of AgNORs per nucleus was 6.88, ranging from 3.73 to 12.70. For group 2, the mean number was 6.97, ranging from 3.63 to 11.67. Statistical analysis using analysis of variance (ANOVA) showed no significant difference between the groups (p=0.33). In our study, AgNOR counts did not prove to be of prognostic value in malignant melanoma. Ronan SG, Farolan MJ, McDonald A, Manaligod JR, Das Gupta TK. Prognostic significance of nucleolar organizer regions (NORs) in malignant melanoma.

Recurrent Lentigo Maligna Melanoma: Regression Associated With Local Azelaic Acid 20%

“…Different human melanoma antigens should be considered as determinants in antitumour response – among others, non‐specific proteins (MAGE 1, MAGE 3, BAGE, GAGE), specific melanosomal proteins (MART‐1, GP100, tyrosinase, TRP‐1), specific mutated proteins (beta‐catenin, MUM‐1 and CD‐4) and carbohydrate epitopes (GM2, GD2, 9–0‐acetyl GD3) 3,4 . Regression seems to represent the ultimate immunological reaction aimed at tumour antigenic complexes but does not exclude further extension of the disease, as illustrated by patients with metastatic melanoma of undetermined origin 5–8 …”

Nucleolar organizer region staining patterns in paraffin‐embedded tissue cells from human skin cancers

“…9 Nevertheless, there are discrepancies among different studies regarding the prognostic value of AgNOR counts in MM. 10 In this work, the NOR patterns of BCC tumors with different severity grades, SCC, and MM were established. Three non-malignant lesions and a cell line were also studied.…”

“…Patients bearing MM tumor stage I, with a high number of NORs, developed metastasis some months earlier than those with fewer NORs 9 . Nevertheless, there are discrepancies among different studies regarding the prognostic value of AgNOR counts in MM 10 …”

Analysis of cell cycle phases and proliferative capacity in mice bearing melanoma maintained on different dietary proteins

“…Patients bearing melanoma tumor stage I, with a high number of NORs, developed metastasis a few months earlier than those with fewer NORs 21 . Nevertheless, there are discrepancies among different studies regarding the prognostic value of AgNOR counts in melanoma 22 …”

“…21 Nevertheless, there are discrepancies among different studies regarding the prognostic value of AgNOR counts in melanoma. 22 Significant correlation between AgNOR value and patient survival has been reported in many types of cancer diseases, showing that the AgNOR quantity is the only significant parameter that predicts patient death. 12 It is known that hypertrophy of the nucleolus is one of the most distinctive cytological features of cancer cells.…”