BAG-4/SODD and associated antiapoptotic proteins are linked to aggressiveness of epithelial ovarian cancer

Christina M. Annunziata, Lilach Kleinberg, Ben Davidson, Aasmund Berner, David Gius, Nana Tchabo, Seth M. Steinberg, Elise C. Kohn

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Purpose: We hypothesized that elevated expression in ovarian cancer of the BAG family of prosurvival proteins and associated partners would be associated with clinical features of aggressiveness in ovarian cancer. Experimental Design: Expression patterns of BAG-1, BAG-3, BAG-4, and Bcl-xL were determined by immunohistochemical analysis of tissue samples obtained at diagnosis from 28 women with stage III or stage IV ovarian cancer treated with cisplatin, paclitaxel, and cyclophosphamide after initial cytoreduction. Association of these proteins, BAG-6, heat shock protein 70 (Hsp70), Hsp27, and Bcl-2, with clinical variables was tested in ovarian cancer tissue arrays from Gynecologic Oncology Group tissue bank. Results: A statistically significant relationship was found between elevated cytoplasmic expression of BAG-4 and improved overall (P = 0.0002) and progression-free survival (P = 0.003) in the prospectively collected samples. Bcl-2 staining was significantly more frequent on the tissue array in lower stage (P = 0.005) and grade (P = 0.0009) tumors,whereas Hsp70 was prominent in higher grade cases (P = 0.002). Furthermore, Bcl-xL was more closely associated with serous compared with endometrioid ovarian cancers (P = 0.004). Conclusion: Unexpectedly, cytoplasmic expression of BAG-4 and Bcl-2 marked less aggressive ovarian cancer, whereas nuclear Hsp70 suggested more aggressive behavior. Bcl-xL may play a more prominent function in the pathology of serous histology ovarian cancers compared with the endometrioid subtype. The findings presented here support involvement of these proteins in the propagation of ovarian cancer and provide a basis for the development of molecular therapeutics modulating these survival pathways.

Original languageEnglish (US)
Pages (from-to)6585-6592
Number of pages8
JournalClinical Cancer Research
Volume13
Issue number22
DOIs
StatePublished - Nov 15 2007
Externally publishedYes

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Ovarian Neoplasms
HSP70 Heat-Shock Proteins
Proteins
Tissue Banks
Ovarian epithelial cancer
Nuclear Proteins
Cyclophosphamide
Disease-Free Survival
Histology
Research Design
Pathology
Staining and Labeling
Survival
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Annunziata, Christina M. ; Kleinberg, Lilach ; Davidson, Ben ; Berner, Aasmund ; Gius, David ; Tchabo, Nana ; Steinberg, Seth M. ; Kohn, Elise C. / BAG-4/SODD and associated antiapoptotic proteins are linked to aggressiveness of epithelial ovarian cancer. In: Clinical Cancer Research. 2007 ; Vol. 13, No. 22. pp. 6585-6592.
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abstract = "Purpose: We hypothesized that elevated expression in ovarian cancer of the BAG family of prosurvival proteins and associated partners would be associated with clinical features of aggressiveness in ovarian cancer. Experimental Design: Expression patterns of BAG-1, BAG-3, BAG-4, and Bcl-xL were determined by immunohistochemical analysis of tissue samples obtained at diagnosis from 28 women with stage III or stage IV ovarian cancer treated with cisplatin, paclitaxel, and cyclophosphamide after initial cytoreduction. Association of these proteins, BAG-6, heat shock protein 70 (Hsp70), Hsp27, and Bcl-2, with clinical variables was tested in ovarian cancer tissue arrays from Gynecologic Oncology Group tissue bank. Results: A statistically significant relationship was found between elevated cytoplasmic expression of BAG-4 and improved overall (P = 0.0002) and progression-free survival (P = 0.003) in the prospectively collected samples. Bcl-2 staining was significantly more frequent on the tissue array in lower stage (P = 0.005) and grade (P = 0.0009) tumors,whereas Hsp70 was prominent in higher grade cases (P = 0.002). Furthermore, Bcl-xL was more closely associated with serous compared with endometrioid ovarian cancers (P = 0.004). Conclusion: Unexpectedly, cytoplasmic expression of BAG-4 and Bcl-2 marked less aggressive ovarian cancer, whereas nuclear Hsp70 suggested more aggressive behavior. Bcl-xL may play a more prominent function in the pathology of serous histology ovarian cancers compared with the endometrioid subtype. The findings presented here support involvement of these proteins in the propagation of ovarian cancer and provide a basis for the development of molecular therapeutics modulating these survival pathways.",
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Annunziata, CM, Kleinberg, L, Davidson, B, Berner, A, Gius, D, Tchabo, N, Steinberg, SM & Kohn, EC 2007, 'BAG-4/SODD and associated antiapoptotic proteins are linked to aggressiveness of epithelial ovarian cancer', Clinical Cancer Research, vol. 13, no. 22, pp. 6585-6592. https://doi.org/10.1158/1078-0432.CCR-07-0327

BAG-4/SODD and associated antiapoptotic proteins are linked to aggressiveness of epithelial ovarian cancer. / Annunziata, Christina M.; Kleinberg, Lilach; Davidson, Ben; Berner, Aasmund; Gius, David; Tchabo, Nana; Steinberg, Seth M.; Kohn, Elise C.

In: Clinical Cancer Research, Vol. 13, No. 22, 15.11.2007, p. 6585-6592.

Research output: Contribution to journalArticle

TY - JOUR

T1 - BAG-4/SODD and associated antiapoptotic proteins are linked to aggressiveness of epithelial ovarian cancer

AU - Annunziata, Christina M.

AU - Kleinberg, Lilach

AU - Davidson, Ben

AU - Berner, Aasmund

AU - Gius, David

AU - Tchabo, Nana

AU - Steinberg, Seth M.

AU - Kohn, Elise C.

PY - 2007/11/15

Y1 - 2007/11/15

N2 - Purpose: We hypothesized that elevated expression in ovarian cancer of the BAG family of prosurvival proteins and associated partners would be associated with clinical features of aggressiveness in ovarian cancer. Experimental Design: Expression patterns of BAG-1, BAG-3, BAG-4, and Bcl-xL were determined by immunohistochemical analysis of tissue samples obtained at diagnosis from 28 women with stage III or stage IV ovarian cancer treated with cisplatin, paclitaxel, and cyclophosphamide after initial cytoreduction. Association of these proteins, BAG-6, heat shock protein 70 (Hsp70), Hsp27, and Bcl-2, with clinical variables was tested in ovarian cancer tissue arrays from Gynecologic Oncology Group tissue bank. Results: A statistically significant relationship was found between elevated cytoplasmic expression of BAG-4 and improved overall (P = 0.0002) and progression-free survival (P = 0.003) in the prospectively collected samples. Bcl-2 staining was significantly more frequent on the tissue array in lower stage (P = 0.005) and grade (P = 0.0009) tumors,whereas Hsp70 was prominent in higher grade cases (P = 0.002). Furthermore, Bcl-xL was more closely associated with serous compared with endometrioid ovarian cancers (P = 0.004). Conclusion: Unexpectedly, cytoplasmic expression of BAG-4 and Bcl-2 marked less aggressive ovarian cancer, whereas nuclear Hsp70 suggested more aggressive behavior. Bcl-xL may play a more prominent function in the pathology of serous histology ovarian cancers compared with the endometrioid subtype. The findings presented here support involvement of these proteins in the propagation of ovarian cancer and provide a basis for the development of molecular therapeutics modulating these survival pathways.

AB - Purpose: We hypothesized that elevated expression in ovarian cancer of the BAG family of prosurvival proteins and associated partners would be associated with clinical features of aggressiveness in ovarian cancer. Experimental Design: Expression patterns of BAG-1, BAG-3, BAG-4, and Bcl-xL were determined by immunohistochemical analysis of tissue samples obtained at diagnosis from 28 women with stage III or stage IV ovarian cancer treated with cisplatin, paclitaxel, and cyclophosphamide after initial cytoreduction. Association of these proteins, BAG-6, heat shock protein 70 (Hsp70), Hsp27, and Bcl-2, with clinical variables was tested in ovarian cancer tissue arrays from Gynecologic Oncology Group tissue bank. Results: A statistically significant relationship was found between elevated cytoplasmic expression of BAG-4 and improved overall (P = 0.0002) and progression-free survival (P = 0.003) in the prospectively collected samples. Bcl-2 staining was significantly more frequent on the tissue array in lower stage (P = 0.005) and grade (P = 0.0009) tumors,whereas Hsp70 was prominent in higher grade cases (P = 0.002). Furthermore, Bcl-xL was more closely associated with serous compared with endometrioid ovarian cancers (P = 0.004). Conclusion: Unexpectedly, cytoplasmic expression of BAG-4 and Bcl-2 marked less aggressive ovarian cancer, whereas nuclear Hsp70 suggested more aggressive behavior. Bcl-xL may play a more prominent function in the pathology of serous histology ovarian cancers compared with the endometrioid subtype. The findings presented here support involvement of these proteins in the propagation of ovarian cancer and provide a basis for the development of molecular therapeutics modulating these survival pathways.

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