Lactate dehydrogenase 5 expression in melanoma increases with disease progression and is associated with expression of Bcl-XL and Mcl-1, but ... View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2009-10-16

AUTHORS

Liqing Zhuang, Richard A Scolyer, Rajmohan Murali, Stanley W McCarthy, Xu Dong Zhang, John F Thompson, Peter Hersey

ABSTRACT

The serum level of lactate dehydrogenase (LDH) is an important predictor of prognosis and treatment response in melanoma patients. It is unknown whether the expression of LDH-5 in tissue sections also has prognostic significance and whether it is related to the expression of the anti-apoptotic proteins, Bcl-2, Bcl-XL and Mcl-1, and endoplasmic reticulum stress protein glucose-regulated protein 78 (GRP78). Identification of an association between LDH-5 expression and anti-apoptotic proteins may have important therapeutic implications for melanoma patients. Sections from 159 pigmented lesions, including nevi and melanoma at different stages of progression were studied by immunohistochemistry. Correlation of LDH-5 expression with clinicopathological factors and with the expression of Bcl-2, Bcl-XL, Mcl-1 and GRP78 was examined. LDH-5 was detected at low levels in 6 of 10 compound nevi (60%) and 6 of 10 dysplastic nevi (60%). The percentage of positive cases was greater in thin (≤1.0 mm) (74%) and thick primary melanoma (>1.0 mm) (95%) and in metastatic melanoma in the skin (100%) and lymph node (81%). The immunoreactive score was highly related to progression of melanoma (P<0.0001). LDH-5 expression was positively associated with increasing tumor thickness (P=0.02) and dermal tumor mitotic rate (P=0.02). LDH-5 above the median immunoreactive score was associated with reduced disease-free survival and overall survival (P<0.02). LDH-5 expression was negatively associated with Bcl-2 expression. In contrast, LDH-5 expression was strongly associated with Bcl-XL and Mcl-1 expression and also positively associated with GRP78 expression (P<0.0001). The low Bcl-2 expression in melanomas with high LDH-5 expression provides an explanation for the poor response of patients with high serum LDH levels to treatment with the Bcl-2 antisense drug ‘Genasense’. The strong correlation of LDH-5 expression with Mcl-1 expression suggests that treatment strategies inhibiting the activity of Mcl-1 in melanoma patients should be investigated. More... »

PAGES

45-53

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/modpathol.2009.129

DOI

http://dx.doi.org/10.1038/modpathol.2009.129

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1053552098

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19838163


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65 disease progression
66 disease-free survival
67 drugs
68 dysplastic nevi
69 explanation
70 expression
71 factors
72 glucose-regulated protein 78
73 high LDH-5 expression
74 high serum LDH levels
75 identification
76 immunohistochemistry
77 immunoreactive score
78 implications
79 important predictor
80 important therapeutic implications
81 increase
82 lactate dehydrogenase
83 lesions
84 levels
85 low Bcl-2 expression
86 low levels
87 lymph nodes
88 median immunoreactive scores
89 melanoma
90 melanoma increases
91 melanoma patients
92 metastatic melanoma
93 mitotic rate
94 nevi
95 nodes
96 overall survival
97 patients
98 percentage
99 pigmented lesions
100 poor response
101 positive cases
102 predictors
103 primary melanoma
104 prognosis
105 prognostic significance
106 progression
107 progression of melanoma
108 protein
109 protein 78
110 rate
111 reduced disease-free survival
112 response
113 scores
114 sections
115 serum LDH levels
116 serum levels
117 significance
118 skin
119 stage
120 strategies
121 strong correlation
122 survival
123 therapeutic implications
124 thick primary melanomas
125 thickness
126 tissue sections
127 treatment
128 treatment response
129 treatment strategies
130 tumor mitotic rate
131 tumor thickness
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