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Expression and clinical role of antiapoptotic proteins of the bag, heat shock, and Bcl-2 families in effusions, primary tumors, and solid metastases in ovarian carcinoma.
Int J Gynecol Pathol. 2009 May; 28(3):211-21.IJ

Abstract

Cancer progression is associated with reduced apoptosis and increased proliferation. We hypothesized that upregulation of the Bag family of survival cochaperones and its molecular partners of the Bcl-2 and heat shock protein (HSP) families would correlate with disease progression and survival in ovarian cancer. Bag-1, Bag-4, HSP27, HSP70, Bcl-2, and Bcl-X(L) expression was immunohistochemically analyzed in effusions (188) and patient-matched solid tumors (43 primary carcinomas, 81 solid metastases). Results were analyzed for anatomic site-related differences, and association with clinicopathologic parameters and survival. Bag-1, Bag-4, and HSP70 were detected in the tumor cell nuclei and cytoplasm, whereas HSP27, Bcl-2, and Bcl-X(L) had exclusively cytoplasmic localization. Antiapoptotic protein expression in effusions differed significantly from primary tumors and metastases. Cytoplasmic Bag-1 (P=0.002), nuclear and cytoplasmic HSP70 (P<0.001), and Bcl-2 (P=0.001) expression was higher in primary carcinomas and solid metastases compared with effusions, whereas Bcl-X(L) (P=0.01), nuclear Bag-1 (P<0.001), nuclear Bag-4 (P=0.01), and cytoplasmic Bag-4 (P=0.002) were upregulated in effusions. Bcl-X(L) expression was associated with poor response to chemotherapy at diagnosis (P=0.02) and HSP27 expression was associated with high-grade tumors (P=0.01). Increased cytoplasmic HSP70 staining in effusions correlated with poor overall survival for the entire cohort (P=0.01). In primary carcinomas, higher Bcl-2 expression correlated with worse overall (P=0.04) and progression-free (P=0.02) survival. Antiapoptotic proteins are differentially expressed in effusions compared with solid tumors, whereas primary carcinomas and solid metastases have comparable expression patterns. HSP70 expression in effusions may be a prognostic marker of poor survival, with a similar role for Bcl-2 in primary carcinomas.

Authors+Show Affiliations

Section for Gynecologic Oncology, Division of Obstetrics and Gynecology, Norwegian Radium Hospital, Oslo, Norway.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19620938

Citation

Elstrand, Mari Bunkholt, et al. "Expression and Clinical Role of Antiapoptotic Proteins of the Bag, Heat Shock, and Bcl-2 Families in Effusions, Primary Tumors, and Solid Metastases in Ovarian Carcinoma." International Journal of Gynecological Pathology : Official Journal of the International Society of Gynecological Pathologists, vol. 28, no. 3, 2009, pp. 211-21.
Elstrand MB, Kleinberg L, Kohn EC, et al. Expression and clinical role of antiapoptotic proteins of the bag, heat shock, and Bcl-2 families in effusions, primary tumors, and solid metastases in ovarian carcinoma. Int J Gynecol Pathol. 2009;28(3):211-21.
Elstrand, M. B., Kleinberg, L., Kohn, E. C., Tropé, C. G., & Davidson, B. (2009). Expression and clinical role of antiapoptotic proteins of the bag, heat shock, and Bcl-2 families in effusions, primary tumors, and solid metastases in ovarian carcinoma. International Journal of Gynecological Pathology : Official Journal of the International Society of Gynecological Pathologists, 28(3), 211-21. https://doi.org/10.1097/PGP.0b013e31818b0f5e
Elstrand MB, et al. Expression and Clinical Role of Antiapoptotic Proteins of the Bag, Heat Shock, and Bcl-2 Families in Effusions, Primary Tumors, and Solid Metastases in Ovarian Carcinoma. Int J Gynecol Pathol. 2009;28(3):211-21. PubMed PMID: 19620938.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Expression and clinical role of antiapoptotic proteins of the bag, heat shock, and Bcl-2 families in effusions, primary tumors, and solid metastases in ovarian carcinoma. AU - Elstrand,Mari Bunkholt, AU - Kleinberg,Lilach, AU - Kohn,Elise C, AU - Tropé,Claes G, AU - Davidson,Ben, PY - 2009/7/22/entrez PY - 2009/7/22/pubmed PY - 2009/10/2/medline SP - 211 EP - 21 JF - International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists JO - Int J Gynecol Pathol VL - 28 IS - 3 N2 - Cancer progression is associated with reduced apoptosis and increased proliferation. We hypothesized that upregulation of the Bag family of survival cochaperones and its molecular partners of the Bcl-2 and heat shock protein (HSP) families would correlate with disease progression and survival in ovarian cancer. Bag-1, Bag-4, HSP27, HSP70, Bcl-2, and Bcl-X(L) expression was immunohistochemically analyzed in effusions (188) and patient-matched solid tumors (43 primary carcinomas, 81 solid metastases). Results were analyzed for anatomic site-related differences, and association with clinicopathologic parameters and survival. Bag-1, Bag-4, and HSP70 were detected in the tumor cell nuclei and cytoplasm, whereas HSP27, Bcl-2, and Bcl-X(L) had exclusively cytoplasmic localization. Antiapoptotic protein expression in effusions differed significantly from primary tumors and metastases. Cytoplasmic Bag-1 (P=0.002), nuclear and cytoplasmic HSP70 (P<0.001), and Bcl-2 (P=0.001) expression was higher in primary carcinomas and solid metastases compared with effusions, whereas Bcl-X(L) (P=0.01), nuclear Bag-1 (P<0.001), nuclear Bag-4 (P=0.01), and cytoplasmic Bag-4 (P=0.002) were upregulated in effusions. Bcl-X(L) expression was associated with poor response to chemotherapy at diagnosis (P=0.02) and HSP27 expression was associated with high-grade tumors (P=0.01). Increased cytoplasmic HSP70 staining in effusions correlated with poor overall survival for the entire cohort (P=0.01). In primary carcinomas, higher Bcl-2 expression correlated with worse overall (P=0.04) and progression-free (P=0.02) survival. Antiapoptotic proteins are differentially expressed in effusions compared with solid tumors, whereas primary carcinomas and solid metastases have comparable expression patterns. HSP70 expression in effusions may be a prognostic marker of poor survival, with a similar role for Bcl-2 in primary carcinomas. SN - 1538-7151 UR - https://www.unboundmedicine.com/medline/citation/19620938/Expression_and_clinical_role_of_antiapoptotic_proteins_of_the_bag_heat_shock_and_Bcl_2_families_in_effusions_primary_tumors_and_solid_metastases_in_ovarian_carcinoma_ L2 - https://doi.org/10.1097/PGP.0b013e31818b0f5e DB - PRIME DP - Unbound Medicine ER -