Immunohistochemical expression of nm23 in primary invasive malignant melanoma is predictive of survival outcome

McDermott, N.; Milburn, Christina; Curran, Bernie; Kay, Elaine W.; Walsh, Caitriona Barry; Leader, M.

doi:10.1002/(sici)1096-9896(200002)190:2<157::aid-path512>3.0.co;2-j

Cited by 16 publications

(15 citation statements)

References 24 publications

(25 reference statements)

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“…1), where there is only 1 IHC-based study or for which all protein data generally agree with each other, gene data do not converge upon that same finding in terms of the direction and/or significance of the effect. In other cases [GRP78 (26), cyclin B1 (32), CDK1 (32), nm23 (33,34), and topoisomerase II (32)], the opposite was observed; gene transcript levels differ while no significant outcome-related effect was observed at the protein level. For the remaining 16 molecules [BCL2 (32,38), survivin (18,32) (28,44), and SPP1/osteopontin (29,45,46)], concordance could not be assessed due to between-study differences making a direct comparison untenable.…”

Section: Bioinformatic Analysismentioning

confidence: 97%

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Melanoma Prognosis: A REMARK-Based Systematic Review and Bioinformatic Analysis of Immunohistochemical and Gene Microarray Studies

Schramm

Mann

2011

Molecular Cancer Therapeutics

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Despite intensive research efforts, within-stage survival rates for melanoma vary widely. Pursuit of molecular biomarkers with improved prognostic significance over clinicohistological measures has produced extensive literature. Reviews have synthesized these data, but none have systematically partitioned highquality studies from the remainder across different molecular methods nor examined system properties of that output. Databases were searched for studies analyzing protein expression by immunohistochemistry (n ¼ 617, extending the only systematic review to date by 102 studies) or for gene expression microarray studies (n ¼ 45) in melanoma in relation to outcome. REMARK-derived criteria were applied to identify highquality studies. Biomarkers and pathways were functionally assessed by using gene ontology software. Most manuscripts did not meet REMARK-based criteria, an ongoing trend that can impede translational research. Across REMARK-compliant literature, 41 proteins were significantly associated with outcome. Multimarker tests consistently emerged among the most promising potential biomarkers, indicating a need to continue assessing candidates in that composite setting. Twenty-one canonical pathways were populated by outcomerelated proteins but not by those that failed to show such an association; we propose that this set of pathways warrants closer investigation to understand drivers of poor outcome in melanoma. Two-gene expression microarray studies met REMARK-based criteria reflecting a genuine paucity of literature in the area. The 254 outcome-related genes were examined for correspondences with the systematically identified protein signature. This analysis highlighted proliferating cell nuclear antigen and survivin as priorities for further examination as biomarkers in melanoma prognosis, and illustrated ongoing need to integrate alternative approaches to biomarker discovery in melanoma translational research.

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Section: Bioinformatic Analysismentioning

confidence: 97%

“…In contrast, 6 molecules were assessed as having no significant relationship with outcome at the protein level but appeared on the Winnepenninckx and colleagues (30) differently expressed gene list [CDK1 (32), cyclin B (32), GRP78 (26), nm23 (33,34), survivin (18,32), and TOPII (32)]. …”

Section: Bioinformatic Analysismentioning

confidence: 99%

Melanoma Prognosis: A REMARK-Based Systematic Review and Bioinformatic Analysis of Immunohistochemical and Gene Microarray Studies

Schramm

Mann

2011

Molecular Cancer Therapeutics

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“…Expression was higher in cancer samples and low expression was significantly associated with a shorter survival. Such prognostic correlation has been described in a variety of tumours including breast (Niu et al, 2002), ovarian (Tas et al, 2002), lung (Katakura et al, 2002) or gastric (Kodera et al, 1994) cancers as well as melanoma (McDermott et al, 2000). However, it remains controversial in CRC with positive (Indinnimeo et al, 1997;Berney et al, 1999;Dursun et al, 2002) and negative (Lindmark, 1996;Lee et al, 2001;Gunther et al, 2002) reports.…”

Section: Validation Studiesmentioning

confidence: 99%

Gene expression profiling of colon cancer by DNA microarrays and correlation with histoclinical parameters

et al. 2004

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Different diagnostic and prognostic groups of colorectal carcinoma (CRC) have been defined. However, accurate diagnosis and prediction of survival are sometimes difficult. Gene expression profiling might improve these classifications and bring new insights into underlying molecular mechanisms. We profiled 50 cancerous and noncancerous colon tissues using DNA microarrrays consisting of B8000 spotted human cDNA. Global hierarchical clustering was to some extent able to distinguish clinically relevant subgroups, normal versus cancer tissues and metastatic versus nonmetastatic tumours. Supervised analyses improved these segregations by identifying sets of genes that discriminated between normal and tumour tissues, tumours associated or not with lymph node invasion or genetic instability, and tumours from the right or left colon. A similar approach identified a gene set that divided patients with significantly different 5-year survival (100% in one group and 40% in the other group; P ¼ 0.005). Discriminator genes were associated with various cellular processes. An immunohistochemical study on 382 tumour and normal samples deposited onto a tissue microarray subsequently validated the upregulation of NM23 in CRC and a downregulation in poor prognosis tumours. These results suggest that microarrays may provide means to improve the classification of CRC, provide new potential targets against carcinogenesis and new diagnostic and/or prognostic markers and therapeutic targets.

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“…80 Some melanoma biomarkers provide Table 3 Summary of cutaneous biomarkers with non-independent prognostic associations.…”

Section: Discussionmentioning

confidence: 99%

“…6,28,[69][70][71][72][73][74][75][76][77][78][79][80][81][82][83][84][85] Since most of these markers are associated with thickness, they will have limited value in the prediction of aggressive behavior in thin melanomas. Nonetheless, as these markers are likely to be involved in melanoma progression, future therapeutic investigations that target the pathways of these markers may be useful, some of which are shown in Table 3.…”

Section: Cutaneous Melanoma Biomarkers Associated With Prognosismentioning

confidence: 99%

Melanoma biomarkers: current status and vision for the future

2008

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Melanoma is the leading cause of death from skin cancer in industrialized countries. Clinical and histological variables such as primary tumor invasion, ulceration, and lymph node status might fail to identify early-stage disease that will eventually progress. Tumor biomarkers might help to identify patients with early-stage melanoma who are likely to develop advanced disease and would benefit from additional therapies. These biomarkers offer the possibility of improved tumor staging through the molecular detection of microscopic lymph node metastases that are not visible on routine histological examination. We focus on biomarkers localized to the tumor tissue and those of prognostic value. We give an overview of the melanoma biomarkers that are most helpful for prediction of patients' outcomes, and discuss the primary melanoma biomarkers that have been shown to be of prognostic significance independent of primary tumor thickness and other common clinical prognostic indicators. Although such tumor-associated biomarkers are thought to have the greatest potential, a lack of reliable data makes their true clinical utility difficult to determine. We conclude that several biomarkers show promise in early studies; however, additional large-scale studies are warranted. We suggest cautious optimism for the field of melanoma biomarkers, which we expect to be translated into clinical practice over the next few years.

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Immunohistochemical expression of nm23 in primary invasive malignant melanoma is predictive of survival outcome

Cited by 16 publications

References 24 publications

Melanoma Prognosis: A REMARK-Based Systematic Review and Bioinformatic Analysis of Immunohistochemical and Gene Microarray Studies

Melanoma Prognosis: A REMARK-Based Systematic Review and Bioinformatic Analysis of Immunohistochemical and Gene Microarray Studies

Gene expression profiling of colon cancer by DNA microarrays and correlation with histoclinical parameters

Melanoma biomarkers: current status and vision for the future

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