Prognostic and predictive significance of ER PR HER-2 NEU NF-kB COX-2 Cyclin D1 and B beta -catenin in breast cancer
0
Citation
0
Reference
20
Related Paper
Cite
Cite
Citations (0)
Abstract Background Prognostic factors in patients who are diagnosed with T4 breast carcinomas are widely awaited. We here evaluated the clinical role of some molecular alterations involved in tumorigenesis in a well-characterized cohort of T4 breast cancer patients with a long follow-up period. Methods A consecutive series of 53 patients with T4 breast carcinoma was enrolled between 1992 and 2001 in Sardinia, and observed up for a median of 125 months. Archival paraffin-embedded tissue sections were used for immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) analyses, in order to assess alterations in expression levels of survivin, p53, and pERK 1-2 proteins as well as in amplification of CyclinD1 and h-prune genes. The Kaplan-Meier and Cox regression methods were used for survival assessment and statistical analysis. Results Overall, patients carrying increased expression of pERK 1-2 (p = 0.027) and survivin (p = 0.008) proteins as well as amplification of h-prune gene (p = 0.045) presented a statistically-significant poorer overall survival in comparison with cases found negative for such alterations. After multivariate analysis, the pathological response to primary chemotherapy and the survivin overexpression in primary carcinoma represented the main parameters with a role as independent prognostic factors in our series. Conclusions Although retrospective, our study identified some molecular parameters with a significant impact on prediction of the response to therapy or prognosis among T4 breast cancer patients. Further large prospective studies are needed in order to validate the use of such markers for the management of these patients.
Surgical oncology
Survivin
Breast carcinoma
Cite
Citations (13)
Cyclin D
Cyclin B
Cite
Citations (207)
Cite
Citations (0)
Cite
Citations (0)
CCND1 encodes for the cyclin D1 protein involved in G1/S cell cycle transition. In breast cancer the mechanism of CCND1 amplification, relationship between cyclin D1 protein expression and the key clinical markers estrogen receptor (ER) and HER2 requires elucidation. Tissue microarrays of primary invasive breast cancer from 93 women were evaluated for CCND1 amplification by fluorescent in-situ hybridization and cyclin D1 protein overexpression by immunohistochemistry. CCND1 amplification was identified in 27/93 (30%) cancers and 59/93 (63%) cancers had overexpression of cyclin D1. CCND1 amplification was significantly associated with cyclin D1 protein overexpression (p < 0.001; Fisher's exact test) and both CCND1 amplification and cyclin D1 protein expression with oestrogen receptor (ER) expression (p = 0.003 and p < 0.001; Fishers exact test). Neither CCND1 amplification nor cyclinD1 expression was associated with tumor size, pathological node status or HER2 amplification, but high CCND1 amplification (Copy Number Gain (CNG) > or = 8) was associated with high tumor grade (p = 0.005; chi square 7.915, 2 df) and worse prognosis by Nottingham Prognostic Index (p = 0.001; 2 sample t-test). High CCND1 amplification (CNG > or = 8) may identify a subset of patients with poor prognosis ER-positive breast cancers who should be considered for additional therapy.
Cite
Citations (88)
Several oncogene aberrations have been found in papillary thyroid cancer, the incidence of which has increased after the accident in Chernoby. The occurrence and prognostic significance of these aberrations may have importance in therapeutic strategies.Tumour tissues from 24 patients were investigated by Dot-blot DNA hybridisation for c-myc, Ha-ras amplification and p53 deletion, and by immunohistochemical method for cyclin D1, p53 and p21 overexpression.Overexpression of p53 protein was detected in 66.6%, with p21 expression (25%) without any influence on tumour phenotype. Cyclin D1 overexpression was found in 50% to be associated with p21, in inverse relation to Iymphocytic infiltration. Overexpression of estrogen receptor was shown in 4 cyclin D1-positive samples (17%).Our results suggest that cyclin D1 overexpression is associated with poor prognosis. The co-expression of cyclin D1 and p21 causes a CDK-independent, estrogen receptor-mediated effect of the cyclin D1 also described in breast cancer.
Cyclin D
Cite
Citations (4)
Cite
Citations (0)
Expression (computer science)
Cite
Citations (0)
Abstract β-catenin is involved in cell adhesion through catenin-cadherin complexes and as a transcriptional regulator in the Wnt signaling pathway. Its deregulation is important in the genesis of a number of human malignancies, particularly colorectal cancer. A range of studies has been undertaken in breast cancer, with contradictory associations reported among β-catenin expression, clinicopathologic variables, and disease outcome. We undertook an immunohistochemical study measuring the levels and subcellular localization of β-catenin in 292 invasive ductal breast cancers with known treatment and outcome. No association with breast cancer–specific death was observed for cytoplasmic or membrane expression alone; however, a continuous score representing both locations (membrane minus cytoplasmic expression: MTC score) was associated with a worse outcome in univariate analysis (P = 0.004), and approached significance in a multivariate analysis model that included lymph node, progesterone receptor (PR), and HER2 status (P = 0.054). Therefore, the MTC score was used for further statistical analyses due to the importance of both the subcellular location and the levels of expression of β-catenin. An association was identified between high cytoplasmic expression (low MTC score), and high tumor grade (P = 0.004), positive Ki67 (P = 0.005), negative estrogen receptor (ER) (P = 0.005), positive HER2 (P = 0.04) status, and an active phosphoinositide 3-kinase pathway (P = 0.005), measured as PIK3CA mutations (P = 0.05) or PTEN loss (P = 0.05). Low cytoplasmic expression (high MTC score) was associated with the luminal A subtype (P = 0.004). In conclusion, a low β-catenin MTC score is associated with an adverse outcome in breast cancer, which may be of mechanistic significance in the disease process. Cancer Epidemiol Biomakers Prev; 19(1); 301–9
Cite
Citations (148)