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The role of Cyclin D1 and Ki‐67 in the development and prognostication of thin melanoma


Kaufmann, Corina; Kempf, Werner; Mangana, Joanna; Cheng, Phil; Emberger, Michael; Lang, Roland; Kaiser, Andreas K; Lattmann, Evelyn; Levesque, Mitchell; Dummer, Reinhard; Koelblinger, Peter (2020). The role of Cyclin D1 and Ki‐67 in the development and prognostication of thin melanoma. Histopathology, 77(3):460-470.

Abstract

Background

Despite their low individual metastatic potential, thin melanomas (≤ 1 mm Breslow thickness) contribute significantly to melanoma mortality overall. Therefore, identification of prognostic biomarkers is particularly important in this subgroup of melanoma. Prompted by pre‐clinical results, we investigated cyclin D1 protein and Ki‐67 expression in in situ, metastatic and non‐metastatic thin melanomas.
Material and Methods

Immunohistochemistry was performed on 112 melanoma specimens, thereof 22 in situ, 48 non‐metastatic and 42 metastatic thin melanomas. Overall, epidermal and dermal cyclin D1 and Ki‐67 expression were semi‐quantitatively evaluated by three independent investigators and compared between groups.
Results

Epidermal Ki‐67 expression did not differ statistically in in situ and invasive melanoma (P = 0.7). Epidermal cyclin D1 expression was significantly higher in thin invasive than in in situ melanoma (P = 0.003).

No difference was found in cyclin D1 expression between metastatic and non‐metastatic invasive tumours. Metastatic and non‐metastatic thin melanomas did not show significant differences in epidermal expression of Ki‐67 and cyclin D1 (P = 0.148 and P = 0.611, respectively). In contrast, strong dermal expression of Ki‐67 was more frequent in metastatic than non‐metastatic samples (28.6 vs. 8.3%, respectively, P = 0.001). The prognostic value of dermal Ki‐67 expression was confirmed by multivariate analysis (P = 0.047).
Conclusion

We found an increased expression of cyclin D1 invasive thin melanomas compared to in situ melanomas which supports a potential role of this protein in early invasion in melanoma, as suggested by pre‐clinical findings. Moreover, our results confirm that high dermal Ki‐67 expression is associated with an increased risk of metastasis development in thin melanoma and could possibly serve as a prognostic biomarker in clinical practice, especially if combined with additional methods.

Abstract

Background

Despite their low individual metastatic potential, thin melanomas (≤ 1 mm Breslow thickness) contribute significantly to melanoma mortality overall. Therefore, identification of prognostic biomarkers is particularly important in this subgroup of melanoma. Prompted by pre‐clinical results, we investigated cyclin D1 protein and Ki‐67 expression in in situ, metastatic and non‐metastatic thin melanomas.
Material and Methods

Immunohistochemistry was performed on 112 melanoma specimens, thereof 22 in situ, 48 non‐metastatic and 42 metastatic thin melanomas. Overall, epidermal and dermal cyclin D1 and Ki‐67 expression were semi‐quantitatively evaluated by three independent investigators and compared between groups.
Results

Epidermal Ki‐67 expression did not differ statistically in in situ and invasive melanoma (P = 0.7). Epidermal cyclin D1 expression was significantly higher in thin invasive than in in situ melanoma (P = 0.003).

No difference was found in cyclin D1 expression between metastatic and non‐metastatic invasive tumours. Metastatic and non‐metastatic thin melanomas did not show significant differences in epidermal expression of Ki‐67 and cyclin D1 (P = 0.148 and P = 0.611, respectively). In contrast, strong dermal expression of Ki‐67 was more frequent in metastatic than non‐metastatic samples (28.6 vs. 8.3%, respectively, P = 0.001). The prognostic value of dermal Ki‐67 expression was confirmed by multivariate analysis (P = 0.047).
Conclusion

We found an increased expression of cyclin D1 invasive thin melanomas compared to in situ melanomas which supports a potential role of this protein in early invasion in melanoma, as suggested by pre‐clinical findings. Moreover, our results confirm that high dermal Ki‐67 expression is associated with an increased risk of metastasis development in thin melanoma and could possibly serve as a prognostic biomarker in clinical practice, especially if combined with additional methods.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Dermatology Clinic
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Pathology and Forensic Medicine
Health Sciences > Histology
Uncontrolled Keywords:Pathology and Forensic Medicine, Histology, General Medicine
Language:English
Date:September 2020
Deposited On:17 Jun 2020 13:00
Last Modified:23 Jul 2024 01:39
Publisher:Wiley-Blackwell Publishing, Inc.
ISSN:0309-0167
OA Status:Hybrid
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1111/his.14139
PubMed ID:32374893
  • Content: Accepted Version