scholarly journals Abnormal FHIT gene transcript and c-myc and c-erbB2 amplification in breast cancer.

2002 ◽  
Vol 49 (2) ◽  
pp. 341-350 ◽  
Author(s):  
Renata Kowara ◽  
Filip Gołebiowski ◽  
Paweł Chrzan ◽  
Jaroslaw Skokowski ◽  
Andrzej Karmolinski ◽  
...  

Searching for ways to improve the characterization of breast cancer we examined the relationship between the status of the FHIT gene transcript and amplification of c-myc and the c-erbB2 oncogene. Abnormal FHIT transcript was detected in 32 of 79 cancers examined. The presence of Fhit protein estimated by Western blots was evident only in cancers exhibiting a normal-sized FHIT transcript. This indicates that abnormal FHIT transcripts observed in our study did not encode any Fhit protein or the amount of such protein was very low. There was no association between the presence of aberrant FHIT gene transcript with age, tumor size, estrogen and progesterone receptor status, local metastases and histological grading. However, the abnormalities in FHIT gene transcripts were observed with different frequency depending on the histopathological type of the tumor. The aberrant FHIT transcript was detected in 60% of lobular cancers and only in 28% of ductal cancers. Analyzing the occurrence of c-myc and c-erbB2 amplification and the presence of aberrant FHIT gene transcripts we found that the aberrant FHIT transcript more frequently occurred in tissues with c-myc amplification. There was a significant (P < 0.05) correlation between the occurrence of the aberrant FHIT gene transcript with accompanying c-myc amplification and positive lymph node status. However, in order to evaluate the predictive value of these findings in breast cancer, an extended clinical follow up will be necessary.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 383-383 ◽  
Author(s):  
Sumit Isharwal ◽  
Hongying Huang ◽  
Gouri Nanjangud ◽  
Francois Audenet ◽  
Yingbei Chen ◽  
...  

383 Background: Micropapillary urothelial carcinoma (MPUC) is a rare but an aggressive variant of urothelial carcinoma. Histologically, most of these tumors are associated with variable amounts of “not otherwise specified (NOS)” urothelial carcinoma. MPUC has been shown to be associated with ERBB2/HER2 amplification and protein overexpression. However, the status and distribution of these findings within the different components of tumors containing both MP and NOS urothelial carcinoma have not been addressed. Methods: We identified 44 cases of MPUC that had tissue available for FISH and IHC at our institute, of which an NOS component sufficient for both FISH and IHC was identified in 37 cases. We followed the updated ASCO/CAP Guidelines for breast cancer and as such amplification was defined by a HER2/CEP17 ratio of ≥ 2.0 or > 6 copies of the gene and HER2 overexpression was considered with IHC scores of 2+ and 3+. Results: In urothelial tumors with both MP and NOS components (n = 37), ERBB2 amplification in MP and NOS components was present in 25 and 16 cases respectively. ERBB2 amplification was significantly higher in the MP component compared to NOS component within the same tumor (67.57% vs. 43.24%, p = 0.049). HER2 overexpression in MP and NOS components was present in 25 and 13 cases respectively. HER2 overexpression was significantly higher in the MP component compared to NOS component within the same tumor (67.56% vs. 35.13%, p = 0.012). In addition, ERBB2 amplification strongly correlated with HER2 overexpression in both MP (rho = 0.65, p < 0.001) and NOS (rho = 0.74, p < 0.001) components. In this cohort (n = 44), tumor stage and lymph node status were significant predictors for overall survival (p = 0.01, < 0.001 respectively). However, ERBB2 amplification and HER2 overexpression in MP component were not associated with patients’ survival outcome (p = 1.00, 0.75 respectively). Conclusions: In MPUC, ERBB2 amplification and HER2 overexpression were preferentially but not exclusively identified in MP component compared to NOS component within the same tumor. Our findings provide evidence for intratumoral heterogeneity of ERBB2 amplification and HER2 expression in MPUC.


2020 ◽  
Vol 6 (6) ◽  
Author(s):  
Yammamah Jawad Abbas ◽  
Fadhil Jawad Al-Tu'ma ◽  
Alaa Fraq Al-Hemerri

Objective: The current study aims to investigate the role of MMP-2 in breast cancer pathogenesis in Iraqi women. Methods: A forty one women with breast cancer and 45 control women were included in this case-control study. Body mass index, age, smoking; married status, tumor size, degree, subtype, lymph node status, pre and postmenopesua included the phenotypic results. The polymerase chain reaction-PCR-allele specific restriction was used to observe the rs243865 polymorphism. Genomic DNA was extracted from whole blood and genotyping with specific prefixes for amplification of the MMP-2 gene was accomplished as enzyme-restricted PCR products were digested, followed by electrophoresis on 1.5% agarose gel. In order to interpret the researchers' results, numerous statistical analyses were applied. Results: The amplicon size of MMP-2 gene was 304 bp, and following its amplification reactions by allelic specific PCR. The amplification product for MMP-2 gene amplification SNP rs243865 gene polymorphism results exhibited one band of 304 bp, two bands of 304 bp and one band 304 bp for individuals have genotype as wild type (CC), homozygous (TT) and heterozygous (CT), respectively. Genotype frequencies of rs243865 polymorphism were found to be consistent with Hardy–Weinberg equilibrium. Allele frequencies of C allele was 0.57, and the T allele was only 0.43 in cases of breast cancer women patient, while the frequencies of CC, CT, and TT genotypes of the rs243865 SNP were statistically significant as 31.7%, 51.2%, 17.1% respectively. Allele frequencies of C and T were 0.78 and 0.22 for the control group, respectively, the heterozygous genotype (CT) was significantly increased the risk of breast cancer women (OR=0.3, 95% CI;0.12 – 0.8 , P≤ 0.05) with respect to those of the CC wild type.  The TT genotype significantly raised the risk of breast cancer women by (OR = 0.2, 95% CI; 0.04 – 0.9, P≤ 0.05). Conclusion: In women with breast cancer, MMP-2 expression is highly association were observed with positive lymph node, histological classification of breast cancer (ll) higher than other classes, and advanced clinical process (ll).


2021 ◽  
Vol 12 (1) ◽  
pp. 4
Author(s):  
Tatiana Kalinina ◽  
Vladislav Kononchuk ◽  
Efim Alekseenok ◽  
Grigory Abdullin ◽  
Sergey Sidorov ◽  
...  

Despite the existing advances in the diagnosis and treatment of breast cancer (BC), the search for markers associated with the clinicopathological features of BC is still in demand. MiRNAs (miRs) have potential as markers, since a change in the miRNA expression profile accompanies the initiation and progression of malignant diseases. The receptors for estrogen, androgen, and progesterone (ER, AR, and PR) play an important role in breast carcinogenesis. Therefore, to search for miRNAs that may function as markers in BC, using bioinformatic analysis and the literature data, we selected 13 miRNAs whose promoter regions contain binding sites for ER or AR, or putative binding sites for ER, AR, and PR. We quantified their expression in MCF-7 cells treated with estradiol, progesterone, or testosterone. The levels of miRNAs sensitive to one or more of these hormones were quantified in BC samples (n = 196). We discovered that high expression levels of miR-190b in breast tumor tissue indicate a positive ER status, and miR-423 and miR-200b levels differ between patients with and without HER2 amplification. The miR-193b, -423, -190a, -324, and -200b levels were associated with tumor size or lymph node status in BC patients, but the presence of these associations depended on the status and expression level of ER, PR, HER2, and Ki-67. We also found that miR-21 expression depends on HER2 expression in ER- and/or PR-positive BC. The levels of miRNA were significantly different between HER2 0 and HER2 1+ tumors (p = 0.027), and between HER2 0 and HER2 2+, 3+ tumors (p = 0.005).


2021 ◽  
Vol 5 (2.1) ◽  
pp. 36
Author(s):  
Zhiyong Liu ◽  
Jian Yi ◽  
Feng’en Liu

Objective: To explore the expression and clinic significance of 8-OHdG in breast cancer. Methods: Pre-operative serum 8-OHdG levels were detected with an enzyme-linked immunosorbent assay in a well-defined series of 173 breast cancer patients. 8-OHdG expression in cancer cells from 150 of these patients was examined by immunohistochemistry. The HPLC-ECD method is used to determine 8-OHdG concentration in urine. Results: The serum 8-OHdG levels and immunohistochemical 8-OHdG expression were in concordance with each other (P < 0.05, r = 0.163). Breast cancer patients with negative 8-OHdG immunostaining show lower survival rate according to the multivariate analysis (P < 0.01). This observation was even more remarkable in ductal carcinomas (n = 140) patients (P < 0.001). A low serum 8-OHdG level was associated statistically significantly with lymphatic vessel invasion and a positive lymph node status. Comparison of 8-OHdG concentration in urine of breast cancer patients and healthy women was statistical significance (P < 0.01). Conclusion: Low serum 8-OHdG levels and a low immunohistochemical 8-OHdG expression were associated with an aggressive breast cancer phenotype. In addition, negative 8-OHdG immunostaining was an independent prognostic factor for breast cancer-specific death in breast carcinoma patients. Using 8-OHdG concentration in urine to predict DNA damage resulting from breast cancer can provide good biological indicators for detecting harm in early breast cancer.


2019 ◽  
Vol 6 (2) ◽  
pp. 2986-2991 ◽  
Author(s):  
Touraj Asvadi Kermani ◽  
Iraj Asvadi Kermani ◽  
Zhaleh Faham ◽  
Roya Dolatkhah

Introduction: Breast cancer (BC) is the most common cancer in women and is the second most common cause of fatality in patients with cancer in the world. Cell proliferation plays an important role in the clinical behavior of invasive BC. We aimed to assess the status of Ki-67 in patients with primary breast cancer and evaluate the association of this tumor marker with other clinico-pathologic and prognostic factors. Methods: The current study recruited 220 patients with primary BC admitted to the oncology clinic of the Tabriz University of Medical Sciences. We evaluated Ki-67 IHC slides and reported the Ki-67 status and its relationship with other prognostic factors in breast cancer patients. Among 220 patients, 63.3% developed grade 2 tumors, and 63.8% were younger than 50-year-olds. 117 cases (53%) were Ki-67 positive with more than 1% tumor nuclei stained, and 53 cases (24%) had tumors with more than 15% of Ki-67 expression. Results: There was no correlation between Ki-67 and patient's age (Spearman rho = 0.375, tau Kendall = 0.374), tumor size (Spearman rho = 0.558, tau Kendall = 0.548) and grade (Spearman rho = 0.570, tau Kendall = 0.568), however, there was a marginally significant relationship between lymph node status and Ki-67 expression (Spearman rho = 0.077, tau Kendall = 0.079). Based on the Mann -Whitney test, there was a significant correlation between the expression of estrogen receptor (ER) and progesterone receptor (PR) with Ki-67. Conclusion: A reliable estimation of different prognostic factors in BC patients is required for the selection of an optimal therapeutic strategy. The attention has been focused on the markers of tumor biology.  


1994 ◽  
Vol 12 (9) ◽  
pp. 1783-1788 ◽  
Author(s):  
T P Johnson ◽  
L Ford ◽  
R B Warnecke ◽  
S G Nayfield ◽  
A Kaluzny ◽  
...  

PURPOSE This study evaluates the effect of the 1988 National Cancer Institute Clinical Alert regarding treatment of early-stage breast cancer on the patterns of treatment provided to patients. PATIENTS AND METHODS Data analyzed were collected from the hospital and outpatient records of 12,534 female patients with a primary diagnosis of breast cancer (stages I and II) initially diagnosed during the years 1983 through 1989. RESULTS Analyses revealed that the proportions of patients with a negative lymph node status diagnosed after the May 1988 Clinical Alert who received adjuvant treatment (tamoxifen and/or multidrug chemotherapy) were significantly greater than predicted from treatment trends established before the Alert's release. Proportions of patients with positive lymph node status receiving adjuvant therapy subsequent to the Alert's release, in contrast, did not fall outside the projected confidence intervals for that group. Additional analyses showed a significant effect of the Clinical Alert among several subgroups of node-negative patients. CONCLUSION Findings suggest that the Clinical Alert mechanism, followed by publication in the peer-reviewed scientific literature, is an effective way to communicate important research findings to practitioners in the community. However, the Alert mechanism is controversial and should be used judiciously to ensure its credibility.


2020 ◽  
Vol 20 (10) ◽  
pp. 1597-1610 ◽  
Author(s):  
Taru Aggarwal ◽  
Ridhima Wadhwa ◽  
Riya Gupta ◽  
Keshav Raj Paudel ◽  
Trudi Collet ◽  
...  

Regardless of advances in detection and treatment, breast cancer affects about 1.5 million women all over the world. Since the last decade, genome-wide association studies (GWAS) have been extensively conducted for breast cancer to define the role of miRNA as a tool for diagnosis, prognosis and therapeutics. MicroRNAs are small, non-coding RNAs that are associated with the regulation of key cellular processes such as cell multiplication, differentiation, and death. They cause a disturbance in the cell physiology by interfering directly with the translation and stability of a targeted gene transcript. MicroRNAs (miRNAs) constitute a large family of non-coding RNAs, which regulate target gene expression and protein levels that affect several human diseases and are suggested as the novel markers or therapeutic targets, including breast cancer. MicroRNA (miRNA) alterations are not only associated with metastasis, tumor genesis but also used as biomarkers for breast cancer diagnosis or prognosis. These are explained in detail in the following review. This review will also provide an impetus to study the role of microRNAs in breast cancer.


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