Candidate genes for testicular cancer evaluated by in situ protein expression analyses on tissue microarrays

Rolf I. Skotheim, Vera M. Abeler, Jahn M. Nesland, Sophie D. Fosså, Ruth Holm, Urs Wagner, Vivi Ann Florenes, Nina Aass, Olli Kallioniemi, Ragnhild A. Lothe (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

42 Citations (Scopus)

Abstract

By the use of high-throughput molecular technologies, the number of genes and proteins potentially relevant to testicular germ cell tumor (TGCT) and other diseases will increase rapidly. In a recent transcriptional profiling, we demonstrated the overexpression of GRB7 and JUP in TGCTs, confirmed the reported overexpression of CCND2. We also have recent evidences for frequent genetic alterations of FHIT and epigenetic alterations of MGMT. To evaluate whether the expression of these genes is related to any clinicopathological variables, we constructed a tissue microarray with 510 testicular tissue cores from 279 patients diagnosed with TGCT, covering various histological subgroups and clinical stages. By immunohistochemistry, we found that JUP, GRB7, CCND2 proteins were rarely present in normal testis, but frequently expressed at high levels in TGCT. Additionally, all premalignant intratubular germ cell neoplasias were JUP-immunopositive. MGMT and FHIT were expressed by normal testicular tissues, but at significantly lower frequencies in TGCT. Except for CCND2, the expressions of all markers were significantly associated with various TGCT subtypes. In summary, we have developed a high-throughput tool for the evaluation of TGCT markers, utilized this to validate five candidate genes whose protein expressions were indeed deregulated in TGCT.
Original languageEnglish
Pages (from-to)397-404
Number of pages8
JournalNeoplasia
Volume5
Issue number5
DOIs
Publication statusPublished - 2003
MoE publication typeA1 Journal article-refereed

Fingerprint

Tissue Array Analysis
Testicular Neoplasms
Genes
Proteins
GRB7 Adaptor Protein
Tumor Biomarkers
Testicular Germ Cell Tumor
Epigenomics
Germ Cells
Testis
Immunohistochemistry
Technology
Gene Expression

Cite this

Skotheim, R. I., Abeler, V. M., Nesland, J. M., Fosså, S. D., Holm, R., Wagner, U., ... Lothe, R. A. (2003). Candidate genes for testicular cancer evaluated by in situ protein expression analyses on tissue microarrays. Neoplasia, 5(5), 397-404. https://doi.org/10.1016/S1476-5586(03)80042-8
Skotheim, Rolf I. ; Abeler, Vera M. ; Nesland, Jahn M. ; Fosså, Sophie D. ; Holm, Ruth ; Wagner, Urs ; Florenes, Vivi Ann ; Aass, Nina ; Kallioniemi, Olli ; Lothe, Ragnhild A. / Candidate genes for testicular cancer evaluated by in situ protein expression analyses on tissue microarrays. In: Neoplasia. 2003 ; Vol. 5, No. 5. pp. 397-404.
@article{9212ab181b464a9fa9377f54438a3134,
title = "Candidate genes for testicular cancer evaluated by in situ protein expression analyses on tissue microarrays",
abstract = "By the use of high-throughput molecular technologies, the number of genes and proteins potentially relevant to testicular germ cell tumor (TGCT) and other diseases will increase rapidly. In a recent transcriptional profiling, we demonstrated the overexpression of GRB7 and JUP in TGCTs, confirmed the reported overexpression of CCND2. We also have recent evidences for frequent genetic alterations of FHIT and epigenetic alterations of MGMT. To evaluate whether the expression of these genes is related to any clinicopathological variables, we constructed a tissue microarray with 510 testicular tissue cores from 279 patients diagnosed with TGCT, covering various histological subgroups and clinical stages. By immunohistochemistry, we found that JUP, GRB7, CCND2 proteins were rarely present in normal testis, but frequently expressed at high levels in TGCT. Additionally, all premalignant intratubular germ cell neoplasias were JUP-immunopositive. MGMT and FHIT were expressed by normal testicular tissues, but at significantly lower frequencies in TGCT. Except for CCND2, the expressions of all markers were significantly associated with various TGCT subtypes. In summary, we have developed a high-throughput tool for the evaluation of TGCT markers, utilized this to validate five candidate genes whose protein expressions were indeed deregulated in TGCT.",
author = "Skotheim, {Rolf I.} and Abeler, {Vera M.} and Nesland, {Jahn M.} and Foss{\aa}, {Sophie D.} and Ruth Holm and Urs Wagner and Florenes, {Vivi Ann} and Nina Aass and Olli Kallioniemi and Lothe, {Ragnhild A.}",
year = "2003",
doi = "10.1016/S1476-5586(03)80042-8",
language = "English",
volume = "5",
pages = "397--404",
journal = "Neoplasia",
issn = "1522-8002",
publisher = "Neoplasia Press",
number = "5",

}

Skotheim, RI, Abeler, VM, Nesland, JM, Fosså, SD, Holm, R, Wagner, U, Florenes, VA, Aass, N, Kallioniemi, O & Lothe, RA 2003, 'Candidate genes for testicular cancer evaluated by in situ protein expression analyses on tissue microarrays', Neoplasia, vol. 5, no. 5, pp. 397-404. https://doi.org/10.1016/S1476-5586(03)80042-8

Candidate genes for testicular cancer evaluated by in situ protein expression analyses on tissue microarrays. / Skotheim, Rolf I.; Abeler, Vera M.; Nesland, Jahn M.; Fosså, Sophie D.; Holm, Ruth; Wagner, Urs; Florenes, Vivi Ann; Aass, Nina; Kallioniemi, Olli; Lothe, Ragnhild A. (Corresponding Author).

In: Neoplasia, Vol. 5, No. 5, 2003, p. 397-404.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Candidate genes for testicular cancer evaluated by in situ protein expression analyses on tissue microarrays

AU - Skotheim, Rolf I.

AU - Abeler, Vera M.

AU - Nesland, Jahn M.

AU - Fosså, Sophie D.

AU - Holm, Ruth

AU - Wagner, Urs

AU - Florenes, Vivi Ann

AU - Aass, Nina

AU - Kallioniemi, Olli

AU - Lothe, Ragnhild A.

PY - 2003

Y1 - 2003

N2 - By the use of high-throughput molecular technologies, the number of genes and proteins potentially relevant to testicular germ cell tumor (TGCT) and other diseases will increase rapidly. In a recent transcriptional profiling, we demonstrated the overexpression of GRB7 and JUP in TGCTs, confirmed the reported overexpression of CCND2. We also have recent evidences for frequent genetic alterations of FHIT and epigenetic alterations of MGMT. To evaluate whether the expression of these genes is related to any clinicopathological variables, we constructed a tissue microarray with 510 testicular tissue cores from 279 patients diagnosed with TGCT, covering various histological subgroups and clinical stages. By immunohistochemistry, we found that JUP, GRB7, CCND2 proteins were rarely present in normal testis, but frequently expressed at high levels in TGCT. Additionally, all premalignant intratubular germ cell neoplasias were JUP-immunopositive. MGMT and FHIT were expressed by normal testicular tissues, but at significantly lower frequencies in TGCT. Except for CCND2, the expressions of all markers were significantly associated with various TGCT subtypes. In summary, we have developed a high-throughput tool for the evaluation of TGCT markers, utilized this to validate five candidate genes whose protein expressions were indeed deregulated in TGCT.

AB - By the use of high-throughput molecular technologies, the number of genes and proteins potentially relevant to testicular germ cell tumor (TGCT) and other diseases will increase rapidly. In a recent transcriptional profiling, we demonstrated the overexpression of GRB7 and JUP in TGCTs, confirmed the reported overexpression of CCND2. We also have recent evidences for frequent genetic alterations of FHIT and epigenetic alterations of MGMT. To evaluate whether the expression of these genes is related to any clinicopathological variables, we constructed a tissue microarray with 510 testicular tissue cores from 279 patients diagnosed with TGCT, covering various histological subgroups and clinical stages. By immunohistochemistry, we found that JUP, GRB7, CCND2 proteins were rarely present in normal testis, but frequently expressed at high levels in TGCT. Additionally, all premalignant intratubular germ cell neoplasias were JUP-immunopositive. MGMT and FHIT were expressed by normal testicular tissues, but at significantly lower frequencies in TGCT. Except for CCND2, the expressions of all markers were significantly associated with various TGCT subtypes. In summary, we have developed a high-throughput tool for the evaluation of TGCT markers, utilized this to validate five candidate genes whose protein expressions were indeed deregulated in TGCT.

U2 - 10.1016/S1476-5586(03)80042-8

DO - 10.1016/S1476-5586(03)80042-8

M3 - Article

VL - 5

SP - 397

EP - 404

JO - Neoplasia

JF - Neoplasia

SN - 1522-8002

IS - 5

ER -