BNIP3 expression in endometrial cancer relates to active hypoxia inducible factor 1alpha pathway and prognosis.
AIMS: BNIP3 is a pro-apoptotic mitochondrial protein induced under hypoxic stress, with the BNIP3 gene being under direct regulation of the hypoxia-inducible HIF-1alpha transcription factor. Induction of BNIP3 leads to caspase-independent necrosis-like cell death and an aggressive tumour phenotype....
| Main Authors: | , , , , |
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| Format: | Journal article |
| Language: | English |
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2008
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| _version_ | 1797099530299113472 |
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| author | Giatromanolaki, A Koukourakis, M Gatter, K Harris, A Sivridis, E |
| author_facet | Giatromanolaki, A Koukourakis, M Gatter, K Harris, A Sivridis, E |
| author_sort | Giatromanolaki, A |
| collection | OXFORD |
| description | AIMS: BNIP3 is a pro-apoptotic mitochondrial protein induced under hypoxic stress, with the BNIP3 gene being under direct regulation of the hypoxia-inducible HIF-1alpha transcription factor. Induction of BNIP3 leads to caspase-independent necrosis-like cell death and an aggressive tumour phenotype. The role of BNIP3 in endometrial cancer was examined. METHODS: The immunohistochemical patterns of BNIP3 expression in 72 early endometrial adenocarcinomas of the endometrioid cell type were studied. Correlation of BNIP3 with the hypoxia-inducible factor HIF-1alpha pathway and with prognosis was also examined. RESULTS: BNIP3 was strongly and extensively expressed in the cytoplasm of cancer cells in 23/72 (31.9%) cases. This high BNIP3 reactivity was not related to histological grade, depth of myometrial invasion or steroid hormone receptor expression. There was, however, a significant association of BNIP3 reactivity with HIF-1alpha (p = 0.04), VEGF (p = 0.04) and, particularly, LDH-5 expression (p = 0.0001). Furthermore, high BNIP3 was associated with poor survival in both univariate (p = 0.05) and multivariate (p = 0.03) models. CONCLUSION: BNIP3 seems to be an important hypoxia-regulated molecule involved in endometrial cancer pathology. Given that high BNIP3 reactivity, being linked with poor post-operative outcome, has been linked with a favourable response to cytotoxic therapy (as previously indicated in experimental studies), high BNIP3 expression may be an indicator for adjuvant chemoradiotherapy in stage I endometrial carcinomas. |
| first_indexed | 2024-03-07T05:25:04Z |
| format | Journal article |
| id | oxford-uuid:e0420920-f65a-433e-94d3-b2e011065d4f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:25:04Z |
| publishDate | 2008 |
| record_format | dspace |
| spelling | oxford-uuid:e0420920-f65a-433e-94d3-b2e011065d4f2022-03-27T09:45:48ZBNIP3 expression in endometrial cancer relates to active hypoxia inducible factor 1alpha pathway and prognosis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e0420920-f65a-433e-94d3-b2e011065d4fEnglishSymplectic Elements at Oxford2008Giatromanolaki, AKoukourakis, MGatter, KHarris, ASivridis, EAIMS: BNIP3 is a pro-apoptotic mitochondrial protein induced under hypoxic stress, with the BNIP3 gene being under direct regulation of the hypoxia-inducible HIF-1alpha transcription factor. Induction of BNIP3 leads to caspase-independent necrosis-like cell death and an aggressive tumour phenotype. The role of BNIP3 in endometrial cancer was examined. METHODS: The immunohistochemical patterns of BNIP3 expression in 72 early endometrial adenocarcinomas of the endometrioid cell type were studied. Correlation of BNIP3 with the hypoxia-inducible factor HIF-1alpha pathway and with prognosis was also examined. RESULTS: BNIP3 was strongly and extensively expressed in the cytoplasm of cancer cells in 23/72 (31.9%) cases. This high BNIP3 reactivity was not related to histological grade, depth of myometrial invasion or steroid hormone receptor expression. There was, however, a significant association of BNIP3 reactivity with HIF-1alpha (p = 0.04), VEGF (p = 0.04) and, particularly, LDH-5 expression (p = 0.0001). Furthermore, high BNIP3 was associated with poor survival in both univariate (p = 0.05) and multivariate (p = 0.03) models. CONCLUSION: BNIP3 seems to be an important hypoxia-regulated molecule involved in endometrial cancer pathology. Given that high BNIP3 reactivity, being linked with poor post-operative outcome, has been linked with a favourable response to cytotoxic therapy (as previously indicated in experimental studies), high BNIP3 expression may be an indicator for adjuvant chemoradiotherapy in stage I endometrial carcinomas. |
| spellingShingle | Giatromanolaki, A Koukourakis, M Gatter, K Harris, A Sivridis, E BNIP3 expression in endometrial cancer relates to active hypoxia inducible factor 1alpha pathway and prognosis. |
| title | BNIP3 expression in endometrial cancer relates to active hypoxia inducible factor 1alpha pathway and prognosis. |
| title_full | BNIP3 expression in endometrial cancer relates to active hypoxia inducible factor 1alpha pathway and prognosis. |
| title_fullStr | BNIP3 expression in endometrial cancer relates to active hypoxia inducible factor 1alpha pathway and prognosis. |
| title_full_unstemmed | BNIP3 expression in endometrial cancer relates to active hypoxia inducible factor 1alpha pathway and prognosis. |
| title_short | BNIP3 expression in endometrial cancer relates to active hypoxia inducible factor 1alpha pathway and prognosis. |
| title_sort | bnip3 expression in endometrial cancer relates to active hypoxia inducible factor 1alpha pathway and prognosis |
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