Nucleolar Diameter and Microvascular Factors as Independent Predictors of Mortality from Malignant Melanoma of the Choroid and Ciliary Body

Al-Jamal, Rana’a T.; Mäkitie, Teemu; Kivelä, Tero

doi:10.1167/iovs.02-1215

Cited by 26 publications

(16 citation statements)

References 38 publications

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“…2004). We have previously confirmed that MLN is a predictor of survival after enucleation in primary uveal melanoma (Al Jamal et al. 2003).…”

Section: Discussionsupporting

confidence: 58%

“…1998; Moshari & McLean 2001). We have proved earlier that MLN is an independent predictor of survival in primary choroidal and ciliary body melanomas (Al Jamal et al. 2003).…”

Section: Introductionmentioning

confidence: 61%

“…1998; Moshari & McLean 2001). We have proved earlier that MLN is an independent predictor of survival in primary choroidal and ciliary body melanomas (Al Jamal et al 2003). We compared MLN in primary uveal melanoma and corresponding hepatic metastasis to determine whether it is associated with tumour progression and whether measuring MLN from hepatic metastasis might aid in predicting survival after dissemination of uveal melanoma.…”

Section: Introductionmentioning

confidence: 93%

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Nucleolar size in choroidal and ciliary body melanomas and corresponding hepatic metastases

Al-Jamal¹,

Toivonen²,

Kivelä³

2010

Acta Ophthalmologica

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. Purpose: This study aimed to investigate the relationship between hepatic metastasis and the mean diameter of the 10 largest nucleoli (MLN) in uveal melanoma. Methods: A cross‐sectional histopathological analysis of 37 metastases (13 surgical or needle biopsies, 24 autopsies) and corresponding primary choroidal and ciliary body melanomas was conducted, using statistical tests appropriate for paired data. The largest nucleoli were measured from digital photographs of silver‐stained sections along a 5‐mm‐wide linear field. Confounders considered were presence of epithelioid cells and microvascular density (MVD), counted as the number of discrete elements labelled by monoclonal antibody QBEND/10 to the CD34 epitope. Results: Hepatic metastases had more frequent epithelioid cells (p = 0.0047) and a higher MVD (median difference, 7.5 counts/0.313 mm2 more; p = 0.044) than their corresponding primary tumours. Hepatic metastases, especially in autopsy specimens rather than surgical biopsies, tended to have a smaller MLN (median 3.6 μm) than the corresponding primary tumour (median difference, 0.55 μm; p = 0.066). The MLN in hepatic metastases was not associated with presence of epithelioid cells and MVD. Overall survival after diagnosis of metastasis was comparable whether hepatic metastases had a large or small MLN (p = 0.95), whereas a high MVD tended to be associated with shorter survival (p = 0.096) among the 13 patients with known survival. Conclusions: The results suggest that MLN is not a useful marker for assessing prognosis after diagnosis of hepatic metastasis from uveal melanoma.

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“…2004). We have previously confirmed that MLN is a predictor of survival after enucleation in primary uveal melanoma (Al Jamal et al. 2003).…”

Section: Discussionsupporting

confidence: 58%

“…1998; Moshari & McLean 2001). We have proved earlier that MLN is an independent predictor of survival in primary choroidal and ciliary body melanomas (Al Jamal et al. 2003).…”

Section: Introductionmentioning

confidence: 61%

Section: Introductionmentioning

confidence: 93%

See 1 more Smart Citation

Nucleolar size in choroidal and ciliary body melanomas and corresponding hepatic metastases

Al-Jamal¹,

Toivonen²,

Kivelä³

2010

Acta Ophthalmologica

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“…Emdogain also acts on genes related to the immune system (Apte et al , 2001; All‐Ericsson et al , 2002; Al‐Jamal et al , 2003). ICA1 is a 69‐kDa peptide autoantigen associated with insulin‐dependent diabetes mellitus (Pietropaolo et al , 1993; Gaedigk et al , 1994, 1996; Winer et al , 2002).…”

Section: Discussionmentioning

confidence: 99%

Effects of Emdogain on osteoblast gene expression

et al. 2006

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“…Poor prognosis has been reported with a number of tumour characteristics including anterior location of melanoma (Seddon et al 1983; Kroll et al 1998; Isager et al 2004), large size tumours mainly with large basal tumour diameter (Shammas & Blodi 1977; Seregard & Kocks 1995; Coleman et al 1996; Damato et al 1996; Isager et al 2006; McLean et al 2004), epitheloid cell type (Seregard & Kock 1995; Mäkitie et al 1999; Singh et al 2001; Al‐Jamal & Kivelä 2006), high number of tumour infiltrating lymphocytes (McLean et al 2004; Niederkorn & Wang 2005) and microvascular channels (Rummelt et al 1995; Mäkitie et al 1999; Al‐Jamal et al 2003; Kivelä et al 2004). With Kaplan‐Meier and Cox regression analyses, it has been shown that the 10‐year melanoma‐specific mortality rate increases with higher numbers of tumour‐infiltrating CD68‐positive macrophages (Mäkitie et al 2001).…”

Section: Introductionmentioning

confidence: 99%

Melanoma Associated Spongiform Scleropathy: Characterization, Biochemical and Immunohistochemical studies

Alyahya

2008

Acta Ophthalmologica

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Summary. Melanoma associated spongiform scleropathy (MASS) is a non‐inflammatory scleral change with a spongiotic morphology seen in association with uveal melanoma. MASS is seen as whitish spindle shaped areas within the sclera that is adjacent to and in contact with a choroidal or ciliary body melanoma. This change can be seen as small scattered lesions in the inner scleral layers or as extensive areas along the whole extent of contact between the tumour and the sclera and involves most of the scleral thickness. MASS changes of different grades of severity were seen in 38% of 363 melanoma eyes investigated. The presence of MASS showed a statistical correlation with age. A significant high incidence of MASS was found in old age groups. This might due to the fact that MASS needs a longer period of contact between the tumour and the sclera to develop. It is also possible that age‐related changes of the extracellular matrix might alter its response to melanoma produced factors leading to the development of MASS. The development of MASS and its severity are influenced by the extent of contact between the tumour and the sclera. This is supported by the significant statistical relation between the largest basal diameter of the tumours and the severity of MASS. Statistical correlation was found between MASS and scleral and extrascleral tumour extension. More than 90% of 82 specimens that showed tumour extension were associated with MASS. A biochemical analysis of scleral samples taken from areas with severe MASS showed a significant reduction of the main amino acids of collagen type I, which is the main scleral collagen. The amounts of total scleral proteins were significantly reduced. This scleral protein reduction is associated with an increase in glycosaminoglycans. These findings indicate a collagen degradation process. Immunohistochemical studies were performed to investigate the expression of matrix metalloproteinases (MMPs). In situ hybridization showed a significantly more frequent and more intense expression of MMP‐2 by scleral fibroblasts in areas with MASS compared with areas without MASS. This was also seen by immunohistochemical staining. Similar high frequency and intense expression of MMP‐2 were seen in tumour infiltrating macrophages. The results of biochemical and immunohistochemical studies indicate a collagen degradation process. This degradation may be the result of the proteolytic enzyme MMP‐2 expressed by scleral fibroblasts under the effect of tumour humeral factors and/or tumour infiltrating macrophages. This scleral degradation results in fragmentation of the scleral collagen fibrils. This along with the accumulation of water in the sclera, as a result of the increase in the production of glycosaminoglycans, results in increase of scleral thickness in MASS areas and forms the histopathological picture of MASS. The scleral degradation may facilitate tumour invasion and may explain the statistical relation between MASS and scleral tumour invasion. MASS was found in a few of the eyes tha...

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Nucleolar Diameter and Microvascular Factors as Independent Predictors of Mortality from Malignant Melanoma of the Choroid and Ciliary Body

Cited by 26 publications

References 38 publications

Nucleolar size in choroidal and ciliary body melanomas and corresponding hepatic metastases

Nucleolar size in choroidal and ciliary body melanomas and corresponding hepatic metastases

Effects of Emdogain on osteoblast gene expression

Melanoma Associated Spongiform Scleropathy: Characterization, Biochemical and Immunohistochemical studies

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