Skip to main content
Top
Published in: Journal of Experimental & Clinical Cancer Research 1/2008

Open Access 01-08-2008 | Research

Nuclear Receptor Interaction Protein (NRIP) expression assay using human tissue microarray and immunohistochemistry technology confirming nuclear localization

Authors: Chih-Ping Han, Ming-Yung Lee, Shu-Ling Tzeng, Chung-Chin Yao, Po-Hui Wang, Ya-Wen Cheng, Show-Li Chen, Teresa S Wu, Yeu-Sheng Tyan, Lai-Fong Kok

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2008

Login to get access

Abstract

Background

A novel human nuclear receptor interaction protein (NRIP) has recently been discovered by Chen SL et al, which may play a role in enhancing the transcriptional activity of steroid nuclear receptors in prostate (LNCaP) and cervical (C33A) cancer cell lines. However, knowledge about the biological functions and clinical implications of NRIP, is still incomplete. Our aim was to determine the distribution of NRIP expression and to delineate the cell types that express NRIP in various malignant tumors and healthy non-pathological tissues. This information will significantly affect the exploration of its physiological roles in healthy and tumor cells.

Methods

By using tissue microarray (TMA) technology and an anti-NRIP monoclonal antibody immunohistochemical (IHC) survey, NRIP expression was examined in 48 types of tumors and in a control group of 48 matched or unmatched healthy non-neoplastic tissues.

Results

Our survey results showed that ten cases were revealed to express the NRIP in six malignancies (esophageal, colon, breast, ovarian, skin, and pancreatic cancers), but not all of these specific tumor types consistently showed positive NRIP expression. Moreover, malignant tumors of the stomach, prostate, liver, lung, kidney, uterine cervix, urinary bladder, lymph node, testis, and tongue revealed no NRIP expression. Among the control group of 48 matched and unmatched non-neoplastic tissues, all of them demonstrated IHC scores less than the cut-off threshold of 3. In addition, ten cores out of thirty-six carcinomatous tissues revealed positive NRIP expression, which indicated that NRIP expression increases significantly in carcinoma tissue cores, comparing to the matched controlled healthy tissues.

Conclusion

This is the first study to use a human TMA and IHC to validate the nuclear localization for this newly identified NRIP expression. In considering the use of NRIP as a potential diagnostic tool for human malignancies survey, it is important to note that NRIP expression carries a sensitivity of only 23%, but has a specificity of 100%. There is also a significant difference in positive NRIP expression between primary carcinomatous tissues and matched controlled healthy tissues. Although further large-scale studies will merit to be conducted to evaluate its role as a potential adjunct for cancer diagnosis, data from this study provides valuable references for the future investigation of the biological functions of NRIP in humans.
Appendix
Available only for authorised users
Literature
1.
go back to reference Tsai TC, Lee YL, Hsiao WC, Tsao YP, Chen SL: NRIP, a Novel Nuclear Receptor Interaction Protein, Enhances the Transcriptional Activity of Nuclear Receptors. J Biol Chem. 280 (20): 20000-9. 10.1074/jbc.M412169200. 2005 May 20 Tsai TC, Lee YL, Hsiao WC, Tsao YP, Chen SL: NRIP, a Novel Nuclear Receptor Interaction Protein, Enhances the Transcriptional Activity of Nuclear Receptors. J Biol Chem. 280 (20): 20000-9. 10.1074/jbc.M412169200. 2005 May 20
2.
go back to reference Chen PH, Tsao YP, Wang CC, Chen SL: Nuclear receptor interaction protein, a coactivator of androgen receptors (AR), is regulated by AR and Sp1 to feed forward and activate its own gene expression through AR protein stability. Nucleic Acids Res. 2008, 36: 51-66. 10.1093/nar/gkm942.CrossRef Chen PH, Tsao YP, Wang CC, Chen SL: Nuclear receptor interaction protein, a coactivator of androgen receptors (AR), is regulated by AR and Sp1 to feed forward and activate its own gene expression through AR protein stability. Nucleic Acids Res. 2008, 36: 51-66. 10.1093/nar/gkm942.CrossRef
3.
go back to reference Mengel M, Kreipe H, von Wasielewski R: Rapid and Large-Scale Transition of New Tumor Biomarkers to Clinical Biopsy Material by Innovative Tissue Microarray Systems. Appl Immunohistochem Mol Morphol. 2003, 11 (3): 261-268.CrossRef Mengel M, Kreipe H, von Wasielewski R: Rapid and Large-Scale Transition of New Tumor Biomarkers to Clinical Biopsy Material by Innovative Tissue Microarray Systems. Appl Immunohistochem Mol Morphol. 2003, 11 (3): 261-268.CrossRef
4.
go back to reference Kallioneimi OP, Wagner U, Kononen J, Sauter G: Tissue microarray technology for high-throughput molecular profiling of cancer. Hum Mol Genet. 2001, 10 (7): 657-62. 10.1093/hmg/10.7.657.CrossRef Kallioneimi OP, Wagner U, Kononen J, Sauter G: Tissue microarray technology for high-throughput molecular profiling of cancer. Hum Mol Genet. 2001, 10 (7): 657-62. 10.1093/hmg/10.7.657.CrossRef
5.
go back to reference Sauter G, Mirlacher M: Tissue microarrays for predictive molecular pathology. J Clin Pathol. 2002, 55 (8): 575-6. 10.1136/jcp.55.8.575.CrossRef Sauter G, Mirlacher M: Tissue microarrays for predictive molecular pathology. J Clin Pathol. 2002, 55 (8): 575-6. 10.1136/jcp.55.8.575.CrossRef
6.
go back to reference Cheng YW, Wu MF, Wang J, Yeh KT, Goan YG, Chiou HL, Vhen VY, Lee H: Human Papillomavirus 16/18 E6 Oncoprotein Is Expressed in Lung Cancer and Related with p53 Inactivation. Cancer Res. 67 (22): 10686-93. 10.1158/0008-5472.CAN-07-1461. 2007 Nov 15 Cheng YW, Wu MF, Wang J, Yeh KT, Goan YG, Chiou HL, Vhen VY, Lee H: Human Papillomavirus 16/18 E6 Oncoprotein Is Expressed in Lung Cancer and Related with p53 Inactivation. Cancer Res. 67 (22): 10686-93. 10.1158/0008-5472.CAN-07-1461. 2007 Nov 15
7.
go back to reference Camp RL, Chung GG, Rimm DL: Automated subcellular localization and quantification of protein expression in tissue microarrays. Nat Med. 2002, 8 (11): 1323-7. 10.1038/nm791. Epub 2002 Oct 21CrossRef Camp RL, Chung GG, Rimm DL: Automated subcellular localization and quantification of protein expression in tissue microarrays. Nat Med. 2002, 8 (11): 1323-7. 10.1038/nm791. Epub 2002 Oct 21CrossRef
8.
go back to reference Cregger M, Berger AJ, Rimm DL: Immunohistochemistry and Quantitative Analysis of Protein Expression. Arch Pathol Lab Med. 2006, 130 (7): 1026-30. Review Cregger M, Berger AJ, Rimm DL: Immunohistochemistry and Quantitative Analysis of Protein Expression. Arch Pathol Lab Med. 2006, 130 (7): 1026-30. Review
9.
go back to reference Revision B: IHC Nuclear Image Analysis User's Guide, MAN-0027, Jan. 2007, 1-43. , Aperio Revision B: IHC Nuclear Image Analysis User's Guide, MAN-0027, Jan. 2007, 1-43. , Aperio
10.
go back to reference McCluggage WG, Sumathi VP, McBride HA, Patterson A: A panel of immunohistochemical stains including carcinoembryonic antigen, vimentin, and estrogen receptor aids in the distinction between primary endometrial and endocervical adenocarcinomas. Int J Gynecol Pathol. 2002, 21: 11-5. 10.1097/00004347-200201000-00003.CrossRef McCluggage WG, Sumathi VP, McBride HA, Patterson A: A panel of immunohistochemical stains including carcinoembryonic antigen, vimentin, and estrogen receptor aids in the distinction between primary endometrial and endocervical adenocarcinomas. Int J Gynecol Pathol. 2002, 21: 11-5. 10.1097/00004347-200201000-00003.CrossRef
11.
go back to reference Khoury T, Tan D, Wang J, Intengan M, Yang J, Alrawi S, Yan P, Byrd JC: Inclusion of Expression of cyclin-dependent kinase inhibitors p16MTS1, p21WAF1, and p27KIP1 in HPV-positive and HPV-negative cervical adenocarcinomas. Virchows Arch. 2001, 439: 55-61. 10.1007/s004280100439.CrossRef Khoury T, Tan D, Wang J, Intengan M, Yang J, Alrawi S, Yan P, Byrd JC: Inclusion of Expression of cyclin-dependent kinase inhibitors p16MTS1, p21WAF1, and p27KIP1 in HPV-positive and HPV-negative cervical adenocarcinomas. Virchows Arch. 2001, 439: 55-61. 10.1007/s004280100439.CrossRef
12.
go back to reference Andra A, Pascual A: Nuclear Hormone Receptors and Gene Expression. Physiol Rev. 2001, 81 (3): 1269-304. Andra A, Pascual A: Nuclear Hormone Receptors and Gene Expression. Physiol Rev. 2001, 81 (3): 1269-304.
13.
go back to reference Diaz LK, Sneige N: Estrogen receptor analysis for breast cancer: current issues and keys to increasing testing accuracy. Adv Anat Pathol. 2005, 12 (1): 10-9. 10.1097/00125480-200501000-00003.CrossRef Diaz LK, Sneige N: Estrogen receptor analysis for breast cancer: current issues and keys to increasing testing accuracy. Adv Anat Pathol. 2005, 12 (1): 10-9. 10.1097/00125480-200501000-00003.CrossRef
14.
go back to reference Allred DC, Harvey JM, Berardo M, Clark GM: Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol. 1998, 11: 155-168. Allred DC, Harvey JM, Berardo M, Clark GM: Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol. 1998, 11: 155-168.
15.
go back to reference Pinder SE, Ellis IO, Elston CW: Prognostic factors in primary breast carcinoma. J Clin Pathol. 1995, 48 (11): 981-3. 10.1136/jcp.48.11.981.CrossRef Pinder SE, Ellis IO, Elston CW: Prognostic factors in primary breast carcinoma. J Clin Pathol. 1995, 48 (11): 981-3. 10.1136/jcp.48.11.981.CrossRef
16.
go back to reference McCarty KS, Szabo E, Flowers JL, Cox EB, Leight GS: Use of a Monoclonal Anti-Estrogen Receptor Antibody in the Immunohistochemical Evaluation of Human Tumors. Cancer Res. 1986, 46 (8 Suppl): 4244s-4248s. McCarty KS, Szabo E, Flowers JL, Cox EB, Leight GS: Use of a Monoclonal Anti-Estrogen Receptor Antibody in the Immunohistochemical Evaluation of Human Tumors. Cancer Res. 1986, 46 (8 Suppl): 4244s-4248s.
17.
go back to reference Packeisen J, Korsching E, Herbst H, Boecker W, Buerger H: Demystified ... Tissue microarray technology. Mol Pathol. 2003, 56: 198-204. 10.1136/mp.56.4.198.CrossRef Packeisen J, Korsching E, Herbst H, Boecker W, Buerger H: Demystified ... Tissue microarray technology. Mol Pathol. 2003, 56: 198-204. 10.1136/mp.56.4.198.CrossRef
18.
go back to reference Chung HH, Ho CL, Chang LY, Lee YL, Chuang SS, Chang MS: Tissue microarray analysis of interleukin-20 expression. Cytokine. 2006, 35 (1–2): 44-52. Chung HH, Ho CL, Chang LY, Lee YL, Chuang SS, Chang MS: Tissue microarray analysis of interleukin-20 expression. Cytokine. 2006, 35 (1–2): 44-52.
Metadata
Title
Nuclear Receptor Interaction Protein (NRIP) expression assay using human tissue microarray and immunohistochemistry technology confirming nuclear localization
Authors
Chih-Ping Han
Ming-Yung Lee
Shu-Ling Tzeng
Chung-Chin Yao
Po-Hui Wang
Ya-Wen Cheng
Show-Li Chen
Teresa S Wu
Yeu-Sheng Tyan
Lai-Fong Kok
Publication date
01-08-2008
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2008
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/1756-9966-27-25

Other articles of this Issue 1/2008

Journal of Experimental & Clinical Cancer Research 1/2008 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine