Inflammation in uveal melanoma

Bronkhorst, Inge H. G.; Jager, Martine J.

doi:10.1038/eye.2012.253

Cited by 85 publications

(69 citation statements)

References 47 publications

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“…We observed that HDAC4 expression was strongest for the cytoplasmic area and intensity in uveal melanoma. HDAC4 is often upregulated in malignancies with excess inflammation and chemokine signalling [30], consistent with an inflammatory phenotype known to enhance the progression of uveal melanoma [31]. In some immune cells, controlled nuclear export of HDAC4 plays an important role in cytokine production [28].…”

Section: Discussionmentioning

confidence: 99%

Tumour Expression of Histone Deacetylases in Uveal Melanoma

et al. 2018

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Purpose: To determine the expression of histone deacetylase enzymes in uveal melanoma tumour cells. Procedures: This is an observational immunohistochemical study of 16 formalin-fixed, paraffin-embedded eyes enucleated for uveal melanoma between January 2001 and March 2002. Haematoxylin and eosin paraffin sections were reviewed for histopathological parameters according to the American Joint Committee on Cancer 7th edition. Sections were then immunohistochemically stained for histone deacetylases 1, 2, 3, 4 and 6 and sirtuin 2 using an automated Leica Bond II platform and Fast Red chromogen, then digitally scanned using Aperio software before assessment of staining. Results: Nuclear expression of histone deacetylases 1, 2, 3, 4 and 6 and of sirtuin 2 was confirmed in uveal melanoma tumour cells. In addition, the tumour cells showed cytoplasmic expression of histone deacetylases 4 and 6 and sirtuin 2. Nuclear and cytoplasmic immunostaining was also seen in intraocular tissues uninvolved by the tumour. Conclusion: Uveal melanoma tumour cells express histone deacetylases 1, 2, 3, 4 and 6 and sirtuin 2, confirming potential tissue targets for histone deacetylase inhibitors.

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Section: Discussionmentioning

confidence: 99%

Tumour Expression of Histone Deacetylases in Uveal Melanoma

et al. 2018

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“…These include a large tumor diameter and prominence, localization in the ciliary body, a high mitotic count, and the presence of epithelioid cells and a leukocytic infiltrate. [6][7][8][9] Specific genetic features are also correlated with prognosis: the importance of chromosome 3 loss and chromosome 8q gain was identified first, [10][11][12] and subsequent studies showed that aberrations such as loss of chromosomes 1p, 6q, and 8p and gain of chromosome 6p have prognostic value as well. [13][14][15] Although loss of one copy of chromosome 3 is the aberration most strongly associated with poor prognosis, a combination with gain of chromosome 8q is more strongly correlated with metastatic UM than either of the two aberrations alone.…”

Section: Methodsmentioning

confidence: 99%

Radiation Treatment Affects Chromosome Testing in Uveal Melanoma

Doğrusöz

Kroes

Duinen

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. The purpose of this study was to determine whether radiation treatment induces chromosomal aberrations in uveal melanoma (UM) and to evaluate which tumor features determine success of karyotyping and FISH. METHODS.Material from 327 UM-containing enucleated eyes was submitted for karyotyping, while FISH for chromosome 3 was performed in 248 samples. Thirty-six UMs had previously undergone irradiation. Karyotypes were analyzed, and the success rate of karyotyping/FISH was evaluated and compared with clinicopathologic tumor characteristics and prior irradiation.RESULTS. Aberrations were observed in all chromosomes, with chromosomes 1, 3,6,8,13,15,16, and Y being altered in at least 15% of the tumors. Aberrations were more common and more complex in previously irradiated tumors (significant for chromosomes 5 [P ¼ 0.004] and 13 [P ¼ 0.04]). Karyotyping and FISH failed significantly more often in irradiated tumors (both P < 0.001). In nonirradiated cases, successful karyotyping was related to a large tumor prominence (P ¼ 0.004) and a high mitotic count (P ¼ 0.007). The success of FISH in these tumors was not associated with any of the studied parameters. In irradiated tumors, karyotyping succeeded more frequently in cases with a high mitotic count (P ¼ 0.03), whereas FISH was more often successful in tumors with a high mitotic count (P ¼ 0.001), a large diameter (P ¼ 0.009) and large prominence (P ¼ 0.008).CONCLUSIONS. Karyotyping and FISH are more often successful in UMs with features characteristic of high tumor aggressiveness, whereas prior irradiation leads to multiple chromosome aberrations and to unsuccessful tests. It will be interesting to determine whether other techniques can provide reliable information on the chromosome status of previously irradiated UMs.

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“…Immune responses against melanoma antigens may play a role in either preventing the growth of the primary tumor or the development of metastases. Indeed, several studies have indicated that an increased expression of HLA molecules confers an increased risk to develop metastases [48,59]. However an association between either the development of UM or its metastases and HLA type was not observed: a recent Dutch large-scale study examined which HLA alleles were related to the development of UM or associated with any specific clinical or tumor characteristics.…”

Section: Somatic Events and Mutationmentioning

confidence: 94%

“…Metastatic death occurs almost exclusively in patients with chromosome 3 loss and/or a specific mRNA gene expression profile, known as class 2 [58]. As has been reported for CM and cancer in general, other parameters related to poor prognosis might include immunological determinants [59]. Immune responses against melanoma antigens may play a role in either preventing the growth of the primary tumor or the development of metastases.…”

Section: Somatic Events and Mutationmentioning

confidence: 97%