Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Diagnostic Pathology
Published in: Diagnostic Pathology 1/2017

Open Access 01-12-2017 | Research

Nucleoli cytomorphology in cutaneous melanoma cells – a new prognostic approach to an old concept

Authors: Piotr Donizy, Przemyslaw Biecek, Agnieszka Halon, Adam Maciejczyk, Rafal Matkowski

Published in: Diagnostic Pathology | Issue 1/2017

Login to get access

Abstract

Background

The nucleolus is an organelle that is an ultrastructural element of the cell nucleus observed in H&E staining as a roundish body stained with eosin due to its high protein content. Changes in the nucleoli cytomorphology were one of the first histopathological characteristics of malignant tumors. The aim of this study was to assess the relationship between the cytomorphological characteristics of nucleoli and detailed clinicopathological parameters of melanoma patients. Moreover, we analyzed the correlation between cytomorphological parameters of nucleoli and immunoreactivity of selected proteins responsible for, among others, regulation of epithelial-mesenchymal transition (SPARC, N-cadherin), cell adhesion and motility (ALCAM, ADAM-10), mitotic divisions (PLK1), cellular survival (FOXP1) and the functioning of Golgi apparatus (GOLPH3, GP73).

Methods

Three characteristics of nucleoli – presence, size and number – of cancer cells were assessed in H&E-stained slides of 96 formalin-fixed paraffin-embedded primary cutaneous melanoma tissue specimens. The results were correlated with classical clinicopathological features and patient survival. Immunohistochemical analysis of the above mentioned proteins was described in details in previous studies.

Results

Higher prevalence and size of nucleoli were associated with thicker and mitogenic tumors. All three nucleolar characteristics were related to the presence of ulceration. Moreover, microsatellitosis was strongly correlated with the presence of macronucleoli and polynucleolization (presence of two or more nucleoli). Lack of immunologic response manifested as no TILs in primary tumor was associated with high prevalence of melanoma cells with distinct nucleoli. Interestingly, in nodular melanoma a higher percentage of melanoma cells with prominent nucleoli was observed. In Kaplan-Meier analysis, increased prevalence and amount, but not size of nucleoli, were connected with shorter cancer-specific and disease-free survival.

Conclusion

(1) High representation of cancer cells with distinct nucleoli, greater size and number of nucleoli per cell are characteristics of aggressive phenotype of melanoma; (2) higher prevalence and size of nucleoli are potential measures of cell kinetics that are strictly correlated with high mitotic rate; and (3) high prevalence of cancer cells with distinct nucleoli and presence of melanocytes with multiple nucleoli are features associated with unfavorable prognosis in patients with cutaneous melanoma.
Literature
1.
Donizy P, Kaczorowski M, Biecek P, Halon A, Matkowski R. Nucleoli and nuclear pseudoinclusions in cutaneous melanoma cells - a new prognostic approach to an old concept. Virchows Arch. 2017;471suppl.1:S117.
2.
Sirri V, Urcuqui-Inchima S, Roussel P, Hernandez-Verdun D. Nucleolus: the fascinating nuclear body. Histochem Cell Biol. 2008;129:13–31.CrossRefPubMed
3.
4.
Derenzini M, Montanaro L, Treré D. What the nucleolus says to a tumour pathologist. Histopathology. 2009;54:753–62.CrossRefPubMed
5.
Visintin R, Amon A. The nucleolus: the magician’s hat for cell cycle tricks. Curr Opin Cell Biol. 2000;12:372–7.CrossRefPubMed
6.
Chubb JR, Boyle S, Perry P, Bickmore WA. Chromatin motion is constrained by association with nuclear compartments in human cells. Curr Biol. 2002;12:439–45.CrossRefPubMed
7.
Zhang LF, Huynh KD, Lee JT. Perinucleolar targeting of the inactive X during S phase: evidence for a role in the maintenance of silencing. Cell. 2007;129:693–706.CrossRefPubMed
8.
9.
Politz JC, Yarovoi S, Kilroy SM, Gowda K, Zwieb C, Pederson T. Signal recognition particle components in the nucleolus. Proc Natl Acad Sci U S A. 2000;97:55–60.CrossRefPubMedPubMedCentral
10.
Leung E, Brown JD. Biogenesis of the signal recognition particle. Biochem Soc Trans. 2010;38:1093–8.CrossRefPubMed
11.
Ganot P, Jady BE, Bortolin ML, Darzacq X, Kiss T. Nucleolar factors direct the 2′-O-ribose methylation and pseudouridylation of U6 spliceosomal RNA. Mol Cell Biol. 1999;19:6906–17.CrossRefPubMedPubMedCentral
12.
YT Y, Shu MD, Narayanan A, Terns RM, Terns MP, Steitz JA. Internal modification of U2 small nuclear (sn)RNA occurs in nucleoli of Xenopus oocytes. J Cell Biol. 2001;152:1279–88.CrossRef
13.
Jellbauer S, Jansen RP. A putative function of the nucleolus in the assembly or maturation of specialized messenger ribonucleoprotein complexes. RNA Biol. 2008;5:225–9.CrossRefPubMed
14.
Ploton D, O'Donohue MF, Cheutin T, Beorchia A, Kaplan H, Thiry M. Three-dimensional organization of rDNA and transcription. The Nucleolus. 2004:154–69. Olson MOJ, editor. New York: Kluwer/Plenum
15.
Raska I, Shaw PJ, Cmarko D. Structure and function of the nucleolus in the spotlight. Curr Opin Cell Biol. 2006;18:325–34.CrossRefPubMed
16.
Donizy P, Zietek M, Halon A, Leskiewicz M, Kozyra C, Matkowski R. Prognostic significance of ALCAM (CD166/MEMD) expression in cutaneous melanoma patients. Diagn Pathol. 2015;2:86.CrossRef
17.
Donizy P, Zietek M, Leskiewicz M, Halon A, Matkowski R. High percentage of ADAM-10 positive melanoma cells correlates with paucity of tumor-infiltrating lymphocytes but does not predict prognosis in cutaneous melanoma patients. Anal Cell Pathol (Amst). 2015;2015:975436.
18.
Pieniazek M, Donizy P, Halon A, Leskiewicz M, Matkowski R. Prognostic significance of immunohistochemical epithelial-mesenchymal transition markers in skin melanoma patients. Biomark Med. 2016;10:975–85.CrossRefPubMed
19.
Donizy P, Kaczorowski M, Biecek P, Halon A, Szkudlarek T, Matkowski R. Golgi-related proteins GOLPH2 (GP73/GOLM1) and GOLPH3 (GOPP1/MIDAS) in cutaneous melanoma: patterns of expression and prognostic significance. Int J Mol Sci. 2016;17:E1619.CrossRefPubMed
20.
Kaczorowski M, Borowiec T, Donizy P, Pagacz K, Fendler W, Lipinski A, Halon A, Matkowski R. Polo-like kinase-1 immunoreactivity is associated with metastases in cutaneous melanoma. J Cutan Pathol. 2017; doi:10.​1111/​cup.​12985 [Epub ahead of print] [Epub ahead of print].
21.
Lee RG, Tsamandas AC, Demetris AJ. Large cell change (liver cell dysplasia) and hepatocellular carcinoma in cirrhosis: matched case-control study, pathological analysis, and pathogenetic hypothesis. Hepatology. 1997;26:1415–22.CrossRefPubMed
22.
Eilers M, Picard D, Yamamoto KR, Bishop JM. Chimaeras of myc oncoprotein and steroid receptors cause hormone-dependent transformation of cells. Nature. 1989;340:66–8.CrossRefPubMed
23.
Arabi A, Wu S, Ridderstrale K, Bierhoff H, Shiue C, Fatyol K, Fahlen S, Hydbring P, Soderberg O, Grummt I, Larsson LG, Wright AP. C-Myc associates with ribosomal DNA and activates RNA polymerase I transcription. Nat Cell Biol. 2005;7:303–10.CrossRefPubMed
24.
Grandori C, Gomez-Roman N, Felton-Edkins ZA, Ngouenet C, Galloway DA, Eisenman RN, White RJ. C-Myc binds to human ribosomal DNA and stimulates transcription of rRNA genes by RNA polymerase I. Nat Cell Biol. 2005;7:311–8.CrossRefPubMed
25.
Grummt I. Life on a planet of its own: regulation of RNA polymerase I transcription in the nucleolus. Genes Dev. 2003;17:1691–702.CrossRefPubMed
26.
Voit R, Hoffmann M, Grummt I. Phosphorylation by G1-specific Cdk-cyclin complexes activates the nucleolar transcription factor UBF. EMBO J. 1999;18:1891–9.CrossRefPubMedPubMedCentral
27.
28.
Cavanaugh AH, Hempel WM, Taylor LJ, Rogalsky V, Todorov G, Rothblum LI. Activity of RNA polymerase I transcription factor UBF blocked by Rb gene product. Nature. 1995;374:177–80.CrossRefPubMed
29.
30.
Donjerkovic D, Scott DW. Regulation of the G1 phase of the mammalian cell cycle. Cell Res. 2000;10:1–16.CrossRefPubMed
31.
Pich A, Chiusa L, Margaria E. Prognostic relevance of AgNORs in tumor pathology. Micron. 2000;31:133–41.CrossRefPubMed
32.
Barzilai A, Goldberg I, Yulash M, Pavlotsky F, Zuckerman A, Trau H, Azizi E, Kopolovic J. Silver-stained nucleolar organizer regions (AgNORs) as a prognostic value in malignant melanoma. Am J Dermatopathol. 1998;20:473–7.CrossRefPubMed
Metadata
Title
Nucleoli cytomorphology in cutaneous melanoma cells – a new prognostic approach to an old concept
Authors
Piotr Donizy
Przemyslaw Biecek
Agnieszka Halon
Adam Maciejczyk
Rafal Matkowski
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Diagnostic Pathology / Issue 1/2017
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/s13000-017-0675-7

Other articles of this Issue 1/2017

Diagnostic Pathology 1/2017 Go to the issue

Review

Molecular genetics of microsatellite-unstable colorectal cancer for pathologists

Research

Composite intestinal adenoma-microcarcinoid in the colon and rectum: a case series and historical review

Case Report

Case report: maternal mosaicism resulting in inheritance of a novel GATA6 mutation causing pancreatic agenesis and neonatal diabetes mellitus

Research

N-myc downstream-regulated gene 2 (NDRG2) promoter methylation and expression in pituitary adenoma

Review

Pleural epithelioid angiosarcoma with lymphatic differentiation arisen after radiometabolic therapy for thyroid carcinoma: immunohistochemical findings and review of the literature

Research

Diagnostic accuracy of oral cancer cytology in a pilot study