Radiological Patterns of Uveal Melanoma Liver Metastases in Correlation to Genetic Status
by
, , , , , ,
Serdar Yavuzyigitoglu
1,2
,
Michael C. Y. Tang
1,
Miguel Jansen
1,
Kaspar W. Geul
3,
Roy S. Dwarkasing
4,
Jolanda Vaarwater
1,2,
Wojtek Drabarek
1,2,
Robert M. Verdijk
5,
Dion Paridaens
1,6,
Nicole C. Naus
1,
Erwin Brosens
2
,
Annelies de Klein
2 and
Emine Kilic
1,* 1
Department of Ophthalmology, Erasmus Medical Centre Rotterdam, 3015 GD Rotterdam, The Netherlands
2
Department of Clinical Genetics, Erasmus Medical Centre Rotterdam, 3015 GD Rotterdam, The Netherlands
3
Department of Internal Medicine, Sint Franciscus Gasthuis Rotterdam, 3045 PM Rotterdam, The Netherlands
4
Department of Radiology, Erasmus Medical Centre Rotterdam, 3015 GD Rotterdam, The Netherlands
5
Department of Pathology, Erasmus Medical Centre Rotterdam, 3015 GD Rotterdam, The Netherlands
6
The Rotterdam Eye Hospital, 3011 BH Rotterdam, The Netherlands
*
Author to whom correspondence should be addressed.
Cancers 2021, 13(21), 5316; https://doi.org/10.3390/cancers13215316
Submission received: 11 October 2021
/
Accepted: 15 October 2021
/
Published: 22 October 2021
(This article belongs to the Special Issue Metastatic Uveal Melanoma)
Simple Summary
Patients with uveal melanoma develop metastases that almost always affect the liver. These liver metastases can have as different metastatic patterns. In this study we investigated the role of the mutation status of the primary tumor in this metastatic process. Mutations in BAP1 or SF3B1 did not correlate with a specific hepatic metastatic pattern, whereas chromosome 1p loss and 8p loss were much more frequent in the primary uveal melanomas of patients who eventually develop miliary metastases in comparison to patients who develop single solitary hepatic metastases. Future endeavors could focus on discovering additional (genetic) factors which influence the propagation and development of hepatic metastases in UM.
Abstract
This study reports the role played by the mutation status of Uveal Melanoma (UM) in relation to hepatic metastatic patterns as seen on imaging modalities. Radiological images were obtained from 123 patients treated at the Erasmus Medical Center Rotterdam or the Rotterdam Eye Hospital. Radiological images were derived from either computed tomography or magnetic resonance imaging. Hepatic metastatic patterns were classified by counting the number of metastases found in the liver. Miliary metastatic pattern (innumerable small metastases in the entire liver) was analyzed separately. Mutation status was determined in 85 patients. Median disease-free survival (DFS) and survival with metastases differed significantly between each of the metastatic patterns (respectively, p = 0.009, p < 0.001), both in favor of patients with less hepatic metastases. The mutation status of the primary tumor was not correlated with any hepatic tumor profiles (p = 0.296). Of the patients who had a solitary metastasis (n = 18), 11 originated from a primary BAP1-mutated tumors and one from a primary SF3B1-mutated tumor. Of the patients who had a miliary metastasis pattern (n = 24), 17 had a primary BAP1-mutated tumor and two had a primary SF3B1-mutated tumor. Chromosome 8p loss was significantly more in patients with more metastases (p = 0.045). Moreover, the primary UMs of patients with miliary metastases harbored more chromosome 8p and 1p loss, compared to patients with single solitary metastasis (p = 0.035 and p = 0.026, respectively). In conclusion, our study shows that there is an inverse correlation of the number of metastasis with the DFS and metastasized survival, indicating separate growth patterns. We also revealed that the number and type of metastases is irrelevant to the prognostic mutation status of the tumor, showing that both BAP1- and SF3B1-mutated UM can result in solitary and miliary metastases, indicating that other processes lay ground to the different metastatic patterns.
Keywords:
uveal melanoma; choroidal melanoma; eye melanoma; BAP1; SF3B1; liver metastases
