scholarly journals Altered Expression of miR-146a-5p and Bcl-2 in Oncocytic Carcinoma of the Breast: A Case Report

Author(s):  
Yumiko Koi ◽  
Yuki Yamamoto ◽  
Saori Fukunaga ◽  
Tatsunari Sasada ◽  
Keiko Kajitani ◽  
...  

Abstract Background: Oncocytic carcinoma of the breast is extremely rare, and its molecular profile is poorly understood. The distinctive feature of oncocytic carcinoma of the breast is that the granular eosinophilic cytoplasm contains numerous mitochondria. Recently, microRNA-146a-5p has been identified as a contributor to carcinogenesis and as a mitochondria-related microRNA, which regulates the mitochondrial function affecting Bcl-2. Bcl-2 plays a role in mitochondrial apoptosis.Case presentation: We report the clinical features, histopathological features, and immunohistochemical and molecular findings of oncocytic carcinoma of the breast in a 76-year-old woman. Immunohistochemistry studies revealed that the tumor cells were positive for antimitochondrial antibody but negative for gross cystic disease fluid protein 15, which confirmed the diagnosis. For molecular profiling, expression of microRNA-146a-5p and Bcl-2 messenger RNA (mRNA), which are mitochondria-related small molecules, were evaluated using real-time reverse transcription polymerase chain reaction. We found that the expression of microRNA-146a-5p was significantly lower (p < 0.01) and that of Bcl-2 mRNA was significantly higher (p < 0.01) compared to the control group (with no specific type of breast cancer). Conclusions: The significant changes in the expression of microRNA-146a-5p and Bcl-2 are specific to oncocytic carcinoma of the breast. Therefore, we suggest that the use of microRNA-146a-5p to target Bcl-2 has a potential therapeutic effect on oncocytic carcinoma of the breast.

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Vivekanand Sharma ◽  
Gajendra Anuragi ◽  
Suresh Singh ◽  
Pinakin Patel ◽  
Arpita Jindal ◽  
...  

Secretory carcinoma of the breast is an extremely rare subtype of breast cancer characterized by intracellular or extracellular secretion and granular eosinophilic cytoplasm of the neoplastic cells. The disease which was considered to be predominant in younger age group has been recognized in adult population too and tends to show slow growth and indolent behavior. The disease occurs preferentially in females and only 27 cases have been reported amongst males. An optimal treatment for the disease subtype has been debated because of the paucity of data. We report two cases (one female and one male) of this rare disease that underwent treatment at our institution.


Author(s):  
S. E. Levine ◽  
A. D. Brinkhous ◽  
K. S. McCarty ◽  
J. A. Mossier ◽  
K.S. McCarty

A variant of ductal carcinoma of the human breast which has been designated apocrine carcinoma has distinctive light and electron microscopic features. Such tumors comprise approximately 0.5% of breast carcinomas. Abundant cytoplasmic membrane bound vesicles (400-600 nm) with dense homogeneous osmophilic cores characterize these tumors. These granules are also seen in apocrine metaplastic breast epithelial lesions1 and appear to be responsible for the finely granular eosinophilic cytoplasm observed by light microscopy. A high content of intermediate affinity non-saturable 4S progesteroneestrogen binding protein (PEBP) in apocrine carcinoma has been reported.2 The present ultrastructural study evaluates the presence of apocrine granules in infiltrating ductal carcinoma (NOS) to determine if a correlation exists between apocrine granule content and the quantity of PEBP present.


2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Keechilat Pavithran ◽  
Divya Pachat ◽  
Dehannathparambil Kottarathil Vijaykumar

Abstract Background Multiple acyl-CoA dehydrogenase deficiency (MAAD) is a rare metabolic disorder resulting from an abnormality in fatty acid oxidation. There are three types of presentations: neonatal onset with or without congenital anomalies and the late-onset type. There is much clinical heterogeneity in the presentation of late-onset variants; hence, the diagnosis is often delayed or missed. Case presentation Here, we report the successful management of a 41-year-old female with late-onset MAAD due to mutation in the ETFDH gene who presented with carcinoma of the breast. Chemotherapy was challenging because there were no previous reports regarding the treatment of such cases. Conclusion The diagnosis was made based on metabolic workup and gene mutation analysis. Unplanned surgery and chemotherapy can be fatal in these patients due to metabolic complications. With proper precautions and monitoring, the patient tolerated surgery and chemotherapy without any complications.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Lukasz Markiewicz ◽  
Dariusz Pytel ◽  
Bartosz Mucha ◽  
Katarzyna Szymanek ◽  
Jerzy Szaflik ◽  
...  

The aim of presented work was to analyze the impact of particular polymorphic changes in the promoter regions of the -1607 1G/2GMMP1, -1562 C/TMMP9, -82 A/GMMP12, -511 C/TIL-1β, and 372 T/CTIMP1genes on their expression level in POAG patients. Blood and aqueous humor samples acquired from 50 patients with POAG and 50 control subjects were used for QPCR and protein levels analysis by ELISA.In vivopromoter activity assays were carried on HTM cells using dual luciferase assay. All studied subjects underwent ophthalmic examination, including BCVA, intraocular pressure, slit-lamp examination, gonioscopy, HRT, and OCT scans. Patients with POAG are characterized by an increased mRNA expression ofMMP1,MMP9,MMP12, andIL-1βgenes as compared to the control group (P<0.001). Aqueous humor acquired from patients with POAG displayed increased protein expression of MMP1, MMP9, MMP12, and IL-1βcompared to the control group (P<0.001). Allele -1607 1G ofMMP1gene possesses only 42,91% of the -1607 2G allele transcriptional activity and allele -1562 C ofMMP9gene possesses only 21,86% of the -1562 T allele. Increased expression levels of metalloproteinases can be considered as a risk factor for the development of POAG.


2021 ◽  
Vol 22 (12) ◽  
pp. 6216
Author(s):  
Monika Englert-Golon ◽  
Mirosław Andrusiewicz ◽  
Aleksandra Żbikowska ◽  
Małgorzata Chmielewska ◽  
Stefan Sajdak ◽  
...  

Ovarian cancer remains the leading cause of death due to gynecologic malignancy. Estrogen-related pathways genes, such as estrogen receptors (ESR1 and ESR2) and their coregulators, proline-, glutamic acid-, and leucine-rich protein 1 (PELP1), and proto-oncogene tyrosine-protein kinase c-Src (SRC) are involved in ovarian cancer induction and development, still they require in-depth study. In our study, tissue samples were obtained from 52 females of Caucasian descent (control group without cancerous evidence (n = 27), including noncancerous benign changes (n = 15), and the ovarian carcinoma (n = 25)). Using quantitative analyses, we investigated ESRs, PELP1, and SRC mRNA expression association with ovarian tumorigenesis. Proteins’ presence and their location were determined by Western blot and immunohistochemistry. Results showed that PELP1 and SRC expression levels were found to differ in tissues of different sample types. The expression patterns were complex and differed in the case of ovarian cancer patients compared to controls. The most robust protein immunoreactivity was observed for PELP1 and the weakest for ESR1. The expression patterns of analyzed genes represent a potentially interesting target in ovarian cancer biology, especially PELP1. This study suggests that specific estrogen-mediated functions in the ovary and ovary-derived cancer might result from different local interactions of estrogen with their receptors and coregulators.


2018 ◽  
pp. 79-86
Author(s):  
A.A. Sukhanova ◽  
◽  
M.Yu. Yegorov ◽  

The objective: to increase the effectiveness of treatment of patients with benign and borderline epithelial ovarian tumors (EOT) after conservative operations performed based on the definition of a high risk group for recurrence and malignancy according to the molecular expression profile of the markers p53, Ki-67, estrogen receptors (ER), CD34 and E-cadherin and inclusion in the complex anti-relapse therapy of the immunomodulating drug Glutoxim. Materials and methods. A clinical examination of 60 patients of reproductive age with EOT was performed, which were treated with organ-sparing surgical treatment (main group). Of these 60 patients, 30 women (subgroup I) were diagnosed with benign EOT (BEOT), the remaining 30 women (subgroup II) were diagnosed with borderline EOT (BoEOT) Ia and Ib stages in FIGO. In removed tumors after routine histopathological examination, the molecular profile was determined by immunohistochemically determining the protein regulator of apoptosis p53, proliferation index (PI) by Ki-67 expression, estrogen receptors — ER, microvessel density by CD34 expression and E-cadherin intercellular adhesion protein. Based on the molecular profile determination data, the removed tumor was ranked as high or low risk of recurrence and malignancy. Patients from the high-risk group for relapse and malignancy according to the molecular profile data included the immunomodulating drug Glutoxim in the complex anti-relapse therapy - intramuscularly 10 mg daily for 2 weeks with a course repeated every six months for 3 years. The control group consisted of 64 patients with BEOT and BoEOT, who underwent conservative surgical treatment without further anti-relapse treatment. Results. During the molecular profile study, it was found that high risk of recurrence and malignancy had EOT with p53 expression (LI ≥15%), high proliferative activity of cells with Ki-67 expression (PI ≥10%), low estrogen reception (LI ER < 49.5%), high density of microvessels on the expression of CD34 (IM ≥40 mv /mm2), low level of intercellular adhesion on the expression of E-cadherin (LI <59%). Molecular profile characterizing a high risk of recurrence and malignancy, in most cases was inherent in BoEOT. The purpose of a comprehensive anti-relapse treatment with the inclusion of the immunomodulatory drug Glutoxim (intramuscularly daily at 10 mg for 2 weeks) after performing of sparing conservative surgical treatment with a repetition of the course every six months in patients at high risk of relapse and malignancy according to molecular profile data has reduced the relapse of EOT to 6.7% in patients of the main group compared with 20.3% in the control group during three years of follow-up observation of patients. The difference is statistically significant (p <0.05). Conclusion. In order to prevent cases of recurrence and malignancy in patients with EOT at high risk of relapse and malignancy according to molecular profile data after a sparing surgical treatment that preserves their reproductive function, it is recommended that Glutoxim is administered in complex anti-relapse therapy at 10 mg intramuscularly per every day for 2 weeks with a repetition of the course every six months for 3 years. Key words: benign epithelial ovarian tumors, borderline epithelial ovarian tumors, high risks of recurrence and malignancy, anti-relapse therapy, reproductive function, Glutoxim.


2003 ◽  
Vol 127 (11) ◽  
pp. 1498-1500
Author(s):  
Melissa A. Pasquale-Styles ◽  
Clara Milikowski

Abstract We describe a rare case of apocrine adenoma of the breast in a 45-year-old man. The patient presented with a tender lump in his left breast that had been present for 6 months. A mammogram identified a 3-mm nodular density in the breast, which was described as a hypoechoic nodule on ultrasound. Microscopic examination of tissue from an excisional biopsy revealed a 3-mm group of benign glands with abundant granular, eosinophilic cytoplasm and apical luminal blebbing, consistent with an apocrine adenoma. After reviewing other reported apocrine adenomas in the literature, we determined that our case was the smallest detected apocrine adenoma to be reported to date.


2014 ◽  
Author(s):  
Γεώργιος Γεωργίου

Βackground: angiogenesis is seen during the multiple stages of carcinogenesis, aswell as during the process of surgical wound healing, a fact which has led tosubstantial debate over the last decades about the potential impact of surgery upon thefinal outcome of ceratin patients treated for breast cancer.Aim: the present research aims at investigating the potential effect of surgery on theprocess of angiogenesis, by studying a number of factors that are related to the latter,in patients suffering from breast cancer before and after the time of the procedure,whilst comparing these results with those of patients that were operated on their breastfor non-malignant disease.Material-Methods: blood from 10 female patients with breast adenocarcinoma(Study Group) was collected via venipuncture before surgery (labeled as PRO), aswell as on post-operative day 3 (labeled as D3) and day 7 (labeled as D7). Moreover,blood samples were also taken from 6 female patients with fibroadenoma (ControlGroup) before surgery (PRO) and on day 3 afetr surgery (D3). These samples weremeasured for detection of circulating levels of three established angiogenesisbiomarkers using ELISA (Enzyme-Linked ImmunoSorbent Assay): VascularEndothelial Growth Factor-A (VEFG-A), Interleukin-8 (IL-8) and basic FibroblastGrowth factor (bFGF or FGF-2). In addition, circulating transcripts of 84 agiogenesirelatedgenes were determined using RT-PCR (Real Time Polymerase ChainReaction). The two groups of patients were firstly compared to each other regardingtheir results. Also, patients belonging to the Study Group were analized at differenttime points regarding surgery. Finally, the results were investigated againstclinicopathological data and patient outcome.Results: using ELISA we were able to detect increased levels of circulating VEGF-Aand IL-8 in the Study Group patients compared to the Control Group patientspreoperatively (p=0,0381 and p=0,0218 respectively), while for bFGF there was nostatistically significant difference documented. Surgery resulted in a significantincrease in VEGF-A levels on D3 (p=0,0389) and D7 (p=0,0172) as compared toPRO levels. Perioperative kinetics of IL-8 showed a mild trend towards increase,which, however, was not statistically significant. Postoperative levels of bFGF wereslightly increased on D3, but on D7 they were even lower than preoperative values(p=0,0205). Using RT-PCR certain differences between the Study Group and theControl Group were recorded regarding the circulating transcripts of a great numberof angiogenesis-related genes preoperatively: upregulation of VEGF-C, EGF, IL-8,FGF-1, SPHK1, NRP1, LAMA5, COL4A3, TEK, EFNA3, EFNB2. AKT1, ITGB3,THBS1, CCL11, TIMP3 and downregulation of CXCL10. Moreover, mastectomyinduced an altered expression in several key-genes in breast cancer patients:upregulation of THBS1, COL4A3, BAI1, ITGB3 and downregulation of EREG,SERPIFN1, CXCL9, CXCL10, IL1B, CCL2, CXCL1, HIF1A, NOTCH4. Conclusions: patients suffering from breast cancer have a different angiogenic profilein comparison to patients with fibroadenoma, as documented through their differencesin circulating levels of angiogenic factors. These levels are greatly changed after thesurgical procedure. VEGF showed a transient increase, while bFGF initially increasedbut only to finally decrease to levels that were even lower than the preoperative ones.Moreover, mastectomy promoted a shift in the expression pattern of a broad panel ofangiogenesis-related gene transcripts.


2019 ◽  
Vol 87 (3) ◽  
pp. 485-493 ◽  
Author(s):  
Magdalena Zasada ◽  
Anna Madetko-Talowska ◽  
Cecilie Revhaug ◽  
Anne Gro W. Rognlien ◽  
Lars O. Baumbusch ◽  
...  

Abstract Background We aimed to identify global blood and retinal gene expression patterns in murine oxygen-induced retinopathy (OIR), a common model of retinopathy of prematurity, which may allow better understanding of the pathogenesis of this severe ocular prematurity complication and identification of potential blood biomarkers. Methods A total of 120 C57BL/6J mice were randomly divided into an OIR group, in which 7-day-old pups were maintained in 75% oxygen for 5 days, or a control group. RNA was extracted from the whole-blood mononuclear cells and retinal cells on days 12, 17, and 28. Gene expression in the RNA samples was evaluated with mouse gene expression microarrays. Results There were 38, 1370 and 111 genes, the expression of which differed between the OIR and control retinas on days 12, 17, and 28, respectively. Gene expression in the blood mononuclear cells was significantly altered only on day 17. Deptor and Nol4 genes showed reduced expression both in the blood and retinal cells on day 17. Conclusion There are sustained marked changes in the global pattern of gene expression in the OIR mice retinas. An altered expression of Deptor and Nol4 genes in the blood mononuclear cells requires further investigation as they may indicate retinal neovascularization.


2009 ◽  
Vol 21 (1) ◽  
pp. 205
Author(s):  
K. E. Park ◽  
R. Cabot

Methylation of the lysine 9 residue of histone H3 (H3K9) is linked with repression of transcription. Dimethylated H3K9 adopts a strict asymmetrical distribution in murine zygotes, with dimethylated H3K9 detectable only on maternally derived chromatin. In contrast, both male and female pronuclei in porcine zygotes can possess dimethylated H3K9; however, some asymmetry in H3K9 dimethylation exists between individual pronuclei, particularly in polyspermic embryos. The objective of this study was to determine the extent that DNA, mRNA, and protein synthesis serve in maintaining the asymmetrical distribution of dimethylated H3K9 in porcine zygotes. We hypothesized that the distribution of dimethylated H3K9 between individual pronuclei would not depend on alternations in chromatin structure induced by DNA or mRNA synthesis but would be affected by protein synthesis. To test this hypothesis, in vitro-matured porcine oocytes were fertilized in vitro, cultured in porcine zygote medium-3 containing 3 mg mL–1 of BSA, and allocated to 1 of 4 treatment groups: (1) incubation with 25 μg mL–1 of α-amanitin (α-AM), (2) incubation with 3 μg mL–1 of aphidicolin (APH), (3) incubation with 50 μg mL–1 of cycloheximide (CYC), and (4) nontreated controls. Embryos were removed from each treatment group at 10, 15, 20, and 25 h post gamete mixing, fixed, and processed to detect dimethylated H3K9 immunocytochemically. For monospermic embryos in the control group, 24% (7/29), 31% (8/26), 30% (7/24), and 20% (4/20) showed differential localization between pronuclei at 10, 15, 20, and 25 h, respectively. For polyspermic embryos in the control group, 82% (32/39), 78% (31/40), 74% (28/38), and 65% (24/37) showed differential localization between pronuclei at 10, 15, 20, and 25 h, respectively. For monospermic embryos in the α-AM group, 29% (4/14), 14% (2/14), 8% (1/12), and 11% (1/9) showed differential localization between pronuclei at 10, 15, 20, and 25 h, respectively. For polyspermic embryos in the α-AM group, 71% (15/21), 63% (12/19), 55% (10/18), and 47% (8/17) showed differential localization between pronuclei at 10, 15, 20, and 25 h, respectively. For monospermic embryos in the APH group, 31% (4/13), 23% (3/13), 23% (3/13), and 18% (2/11) showed differential localization between pronuclei at 10, 15, 20, and 25 h, respectively. For polyspermic embryos in the APH group, 75% (15/20), 67% (12/18), 63% (12/19), and 56% (10/18) showed differential localization between pronuclei at 10, 15, 20, and 25 h, respectively. For monospermic embryos in the CYC group, 33% (5/15), 25% (4/16), 14% (2/14), and 9% (1/11) showed differential localization between pronuclei at 10, 15, 20, and 25 h, respectively. For polyspermic embryos in the CYC group, 78% (18/23), 67% (16/24), 58% (14/24), and 59% (13/22) showed differential localization between pronuclei at 10, 15, 20, and 25 h, respectively. These results suggest that the distribution of dimethylated H3K9 between pronuclei is not affected by DNA, mRNA, or protein synthesis (P > 0.05), but is affected by the age of the pronuclei (P < 0.05).


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