Association between gene expression profile, proliferation and metastasis in uveal melanoma

Michael D. Onken, Lori A. Worley, J. William Harbour

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Purpose: Uveal melanomas cluster into two molecular groups based on their gene expression profile. Tumors with the class 1 signature rarely metastasize, whereas those with the class 2 signature have a very high rate of metastasis. However, the biological basis for this metastatic propensity of class 2 tumors remains unclear. Towards such an explanation, this study was conducted to determine whether class 2 tumors have a higher proliferative rate than class 1 tumors. Materials and Methods: The study included 28 primary uveal melanomas with extensive clinical, pathologic, and genetic annotation, including age, gender, ciliary body involvement, tumor basal diameter, thickness, cell type, gene expression profile, status of chromosomes 3 and 8p, aneuploidy, and clinical outcome. Immunopositivity for Ki-67 was determined by counting all positive nuclei in representative whole tumor sections. Results: Ki-67 positivity was significantly associated with class 2 gene expression profile, loss of chromosome 3 and increased aneuploidy (P0.04, P0.004, and P0.03, respectively). Ki-67 positivity showed a borderline significant association with epithelioid cell type (P0.07). Receiver operating characteristic (ROC) analysis of Ki-67 positivity, using the class 2 signature as an endpoint, identified a Ki-67 score of approximately 20 cells per high power field as the optimal cut-off point between low and high risk for metastasis (log rank test, P0.01). Conclusions: On average, class 2 uveal melanomas have a higher proliferative rate than class 1 tumors. Further work is needed to determine whether loss of chromosome 3, increased aneuploidy, or other factors may be responsible for the increased proliferation.

Original languageEnglish
Pages (from-to)857-863
Number of pages7
JournalCurrent Eye Research
Volume35
Issue number9
DOIs
StatePublished - Sep 1 2010
Externally publishedYes

Fingerprint

Transcriptome
Neoplasm Metastasis
Chromosomes, Human, Pair 3
Aneuploidy
Neoplasms
Epithelioid Cells
Ciliary Body
Uveal melanoma
ROC Curve

Keywords

  • Choroid
  • Ciliary body
  • Eye
  • Gene expression profile
  • Metastasis
  • Proliferation
  • Survival
  • Uveal melanoma

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Association between gene expression profile, proliferation and metastasis in uveal melanoma. / Onken, Michael D.; Worley, Lori A.; William Harbour, J.

In: Current Eye Research, Vol. 35, No. 9, 01.09.2010, p. 857-863.

Research output: Contribution to journalArticle

@article{59809681e25a498a80bb6bb6217e2ede,
title = "Association between gene expression profile, proliferation and metastasis in uveal melanoma",
abstract = "Purpose: Uveal melanomas cluster into two molecular groups based on their gene expression profile. Tumors with the class 1 signature rarely metastasize, whereas those with the class 2 signature have a very high rate of metastasis. However, the biological basis for this metastatic propensity of class 2 tumors remains unclear. Towards such an explanation, this study was conducted to determine whether class 2 tumors have a higher proliferative rate than class 1 tumors. Materials and Methods: The study included 28 primary uveal melanomas with extensive clinical, pathologic, and genetic annotation, including age, gender, ciliary body involvement, tumor basal diameter, thickness, cell type, gene expression profile, status of chromosomes 3 and 8p, aneuploidy, and clinical outcome. Immunopositivity for Ki-67 was determined by counting all positive nuclei in representative whole tumor sections. Results: Ki-67 positivity was significantly associated with class 2 gene expression profile, loss of chromosome 3 and increased aneuploidy (P0.04, P0.004, and P0.03, respectively). Ki-67 positivity showed a borderline significant association with epithelioid cell type (P0.07). Receiver operating characteristic (ROC) analysis of Ki-67 positivity, using the class 2 signature as an endpoint, identified a Ki-67 score of approximately 20 cells per high power field as the optimal cut-off point between low and high risk for metastasis (log rank test, P0.01). Conclusions: On average, class 2 uveal melanomas have a higher proliferative rate than class 1 tumors. Further work is needed to determine whether loss of chromosome 3, increased aneuploidy, or other factors may be responsible for the increased proliferation.",
keywords = "Choroid, Ciliary body, Eye, Gene expression profile, Metastasis, Proliferation, Survival, Uveal melanoma",
author = "Onken, {Michael D.} and Worley, {Lori A.} and {William Harbour}, J.",
year = "2010",
month = "9",
day = "1",
doi = "10.3109/02713683.2010.493265",
language = "English",
volume = "35",
pages = "857--863",
journal = "Current Eye Research",
issn = "0271-3683",
publisher = "Informa Healthcare",
number = "9",

}

TY - JOUR

T1 - Association between gene expression profile, proliferation and metastasis in uveal melanoma

AU - Onken, Michael D.

AU - Worley, Lori A.

AU - William Harbour, J.

PY - 2010/9/1

Y1 - 2010/9/1

N2 - Purpose: Uveal melanomas cluster into two molecular groups based on their gene expression profile. Tumors with the class 1 signature rarely metastasize, whereas those with the class 2 signature have a very high rate of metastasis. However, the biological basis for this metastatic propensity of class 2 tumors remains unclear. Towards such an explanation, this study was conducted to determine whether class 2 tumors have a higher proliferative rate than class 1 tumors. Materials and Methods: The study included 28 primary uveal melanomas with extensive clinical, pathologic, and genetic annotation, including age, gender, ciliary body involvement, tumor basal diameter, thickness, cell type, gene expression profile, status of chromosomes 3 and 8p, aneuploidy, and clinical outcome. Immunopositivity for Ki-67 was determined by counting all positive nuclei in representative whole tumor sections. Results: Ki-67 positivity was significantly associated with class 2 gene expression profile, loss of chromosome 3 and increased aneuploidy (P0.04, P0.004, and P0.03, respectively). Ki-67 positivity showed a borderline significant association with epithelioid cell type (P0.07). Receiver operating characteristic (ROC) analysis of Ki-67 positivity, using the class 2 signature as an endpoint, identified a Ki-67 score of approximately 20 cells per high power field as the optimal cut-off point between low and high risk for metastasis (log rank test, P0.01). Conclusions: On average, class 2 uveal melanomas have a higher proliferative rate than class 1 tumors. Further work is needed to determine whether loss of chromosome 3, increased aneuploidy, or other factors may be responsible for the increased proliferation.

AB - Purpose: Uveal melanomas cluster into two molecular groups based on their gene expression profile. Tumors with the class 1 signature rarely metastasize, whereas those with the class 2 signature have a very high rate of metastasis. However, the biological basis for this metastatic propensity of class 2 tumors remains unclear. Towards such an explanation, this study was conducted to determine whether class 2 tumors have a higher proliferative rate than class 1 tumors. Materials and Methods: The study included 28 primary uveal melanomas with extensive clinical, pathologic, and genetic annotation, including age, gender, ciliary body involvement, tumor basal diameter, thickness, cell type, gene expression profile, status of chromosomes 3 and 8p, aneuploidy, and clinical outcome. Immunopositivity for Ki-67 was determined by counting all positive nuclei in representative whole tumor sections. Results: Ki-67 positivity was significantly associated with class 2 gene expression profile, loss of chromosome 3 and increased aneuploidy (P0.04, P0.004, and P0.03, respectively). Ki-67 positivity showed a borderline significant association with epithelioid cell type (P0.07). Receiver operating characteristic (ROC) analysis of Ki-67 positivity, using the class 2 signature as an endpoint, identified a Ki-67 score of approximately 20 cells per high power field as the optimal cut-off point between low and high risk for metastasis (log rank test, P0.01). Conclusions: On average, class 2 uveal melanomas have a higher proliferative rate than class 1 tumors. Further work is needed to determine whether loss of chromosome 3, increased aneuploidy, or other factors may be responsible for the increased proliferation.

KW - Choroid

KW - Ciliary body

KW - Eye

KW - Gene expression profile

KW - Metastasis

KW - Proliferation

KW - Survival

KW - Uveal melanoma

UR - http://www.scopus.com/inward/record.url?scp=77956149503&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77956149503&partnerID=8YFLogxK

U2 - 10.3109/02713683.2010.493265

DO - 10.3109/02713683.2010.493265

M3 - Article

C2 - 20795869

AN - SCOPUS:77956149503

VL - 35

SP - 857

EP - 863

JO - Current Eye Research

JF - Current Eye Research

SN - 0271-3683

IS - 9

ER -