Impact of BCL2 and p53 on postmastectomy radiotherapy response in high-risk breast cancer. A subgroup analysis of DBCG82 b&amp;c

Kyndi, Marianne; Sørensen, Flemming Brandt; Knudsen, Helle; Alsner, Jan; Overgaard, Marie; Nielsen, Hanne Melgaard; Overgaard, Jens

doi:10.1080/02841860802050746

Cited by 19 publications

(9 citation statements)

References 43 publications

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“…and ER-tumours was found to be statistically significant. A positive correlation between BCL2 expression and PR was also found (P \ 0.001) as reported by Lee et al [7], Kyndi et al [38].…”

Section: Discussionsupporting

confidence: 76%

Bcl-2 expression and triple negative profile in breast carcinoma

et al. 2010

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Many biomarkers for breast cancer prognosis have been proposed during the last two decades, among which HER2 and oestrogen receptors are of common use in routine clinical practice. However, in recent years, BCL2 has been recognized as an important prognostic parameter in human breast cancer, although its clinical utility is well established. The aim of this study was to examine the protein expression patterns of BCL2, HER2, oestrogen (ER) and progesterone receptors (PR) and to evaluate their correlation with survival and other prognostic parameters such as tumour size, histological grade and metastasis. We used a retrospective study including 84 Tunisian women with breast cancer. Immunohistochemistry was used to measure protein expression levels of several biomarkers. Association with conventional biopathological factors was analysed by SPSS (version13). The expression rates of BCL2, HER2, ER and PR were, respectively, 69, 62, 58.3 and 51.2%. In univariate analyses, BCL2 was highly correlated with both PR (P < 0.001) and ER (P = 0.006) and also with HER2 expression (P = 0.001). The triple negative profile showed a significant association with SBR (P = 0.016) and BCL2 expression (P = 0.02). In multivariate analyses, a significant association was maintained between BCL2 and both PR and ER (P = 0.02 and P = 0.004, respectively). Survival analysis showed that BCL2 expression was positively correlated with patients survival (P = 0.032). A Bayesian network analysis of all the variables confirmed the high value of BCL2 expression as a predictor of survival. As conclusion, BCL2 expression seems to be a very useful factor that should be in combination with HER2 and ER in breast cancer prognosis.

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“…and ER-tumours was found to be statistically significant. A positive correlation between BCL2 expression and PR was also found (P \ 0.001) as reported by Lee et al [7], Kyndi et al [38].…”

Section: Discussionsupporting

confidence: 76%

Bcl-2 expression and triple negative profile in breast carcinoma

et al. 2010

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“…Normal breast tissue from healthy women shows lower expression of Bcl-2 protein than normal breast tissue in women with cancer and in cancer tissue [40]. In breast carcinoma, Bcl-2 has been described as an independent prognostic and predictive marker [41,42,43] and loss of its expression in high risk breast carcinoma has been related to increased overall mortality, distinct metastasis and locoregional recurrence [44]. In Bcl-2 positive tumors Pinzon-Charry provided evidence of good prognosis related to CD40 expression [32,33] as we have done in this study.…”

Section: Discussionmentioning

confidence: 99%

Analysis of CD40 expression in breast cancer and its relation to clinicopathological characteristics.

Slobodova¹,

Ehrmann²,

Krejčí³

et al. 2011

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Breast cancer is currently the most common cancer in women worldwide. For this reason, new biomarkers for better predicting response to treatment are needed. CD40, described as expressed in haematological and epithelial tumors, is linked to apoptosis and offers promise as a new predictive/ prognostic marker. We evaluated CD40 expression in formalin-fixed, paraffin-embedded samples from 181 breast carcinomas using immunohistochemical staining with CD40 antibody. Samples were divided according to hormone (oestrogen receptor /ER/, progesterone receptor /PR/) and her-2/neu status into groups: 1.Luminal A (ER+PR+her-2/neu-), 2. Luminal B (ER+PR+her-2/neu+), 3.Triple-negative (ER-PR-her-2/neu-) and 4. Her-2/neu (ER-PR-her-2/neu+). The results of CD40 staining were correlated with clinicopathological data. CD40 was found to be expressed in membrane, cytoplasm and nucleus. Normal ducts expressed cytoplasmic CD40 in 30% of cases, in breast tumor ducts in 53% of cases. CD40 was evaluated as an independent marker and significant positive correlation was found with Bcl-2 (p =0.002), early stage (p =0.016) and preoperative chemotherapy (p =0.043). There was higher overall survival for patients with cytoplasmic CD40 expression (0.05). Differences in expression of cytoplasmic CD40 between groups with different hormonal and her-2/neu status were statistically highly significant (p=0.00003). In groups with different hormonal status, a positive statistical correlation was found for the luminal A group with relapse (p=0.024) and stage (p=0.006). No correlation was found with age, disease onset, family history of cancer/ breast cancer, patient history, hormonal replacement therapy, menopausal status at onset of disease, adjuvant chemotherapeutic treatment or disease free survival. Nuclear expression of CD40 was found to be unrelated to any clinicopathological data. However, there was higher ratio of positive cases in cancer cases (83%) than in normal tissue (30%). In conclusion, cytoplasmic expression of CD40 is related to factors connected to better prognosis and suggest that CD40 may have potential as a new prognostic factor in breast cancer.

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“…In the DBCG82 cohort, tissue microarrays (TMAs) [13] were used for immunohistochemical staining of the p53 antigen [14]. Antigen retrieval was carried out by microwaving the TMA sections in T-EG buffer (Tris 10 mM'EGTA 0.5 mM, pH 9.0) twice for 5 minutes followed by incubation with a monoclonal anti-p53 antibody (p-53 protein DO-7 code K4001, Dako, Glostrup, Denmark) diluted 1:600 in Antibody Diluent (Dako, Glostrup, Denmark) overnight at 48C.…”

Section: P53 Evaluation By Immunohistochemistrymentioning

confidence: 99%