BackgroundBreast cancer brain metastases (BCBM) develop in about 20–30% of breast cancer (BC) patients. BCBM are associated with dismal prognosis not at least due to lack of valuable molecular therapeutic targets. The aim of the study was to identify new molecular biomarkers and targets in BCBM by using complementary state-of-the-art techniques.MethodsWe compared array expression profiles of three BCBM with 16 non-brain metastatic BC and 16 primary brain tumors (prBT) using a false discovery rate (FDR) p < 0.05 and fold change (FC) > 2. Biofunctional analysis was conducted on the differentially expressed probe sets. High-density arrays were employed to detect copy number variations (CNVs) and whole exome sequencing (WES) with paired-end reads of 150 bp was utilized to detect gene mutations in the three BCBM.ResultsThe top 370 probe sets that were differentially expressed between BCBM and both BC and prBT were in the majority comparably overexpressed in BCBM and included, e.g. the coding genes BCL3, BNIP3, BNIP3P1, BRIP1, CASP14, CDC25A, DMBT1, IDH2, E2F1, MYCN, RAD51, RAD54L, and VDR. A number of small nucleolar RNAs (snoRNAs) were comparably overexpressed in BCBM and included SNORA1, SNORA2A, SNORA9, SNORA10, SNORA22, SNORA24, SNORA30, SNORA37, SNORA38, SNORA52, SNORA71A, SNORA71B, SNORA71C, SNORD13P2, SNORD15A, SNORD34, SNORD35A, SNORD41, SNORD53, and SCARNA22. The top canonical pathway was entitled, role of BRCA1 in DNA damage response. Network analysis revealed key nodes as Akt, ERK1/2, NFkB, and Ras in a predicted activation stage. Downregulated genes in a data set that was shared between BCBM and prBT comprised, e.g. BC cell line invasion markers JUN, MMP3, TFF1, and HAS2. Important cancer genes affected by CNVs included TP53, BRCA1, BRCA2, ERBB2, IDH1, and IDH2. WES detected numerous mutations, some of which affecting BC associated genes as CDH1, HEPACAM, and LOXHD1.ConclusionsUsing complementary molecular genetic techniques, this study identified shared and unshared molecular events in three highly aberrant BCBM emphasizing the challenge to detect new molecular biomarkers and targets with translational implications. Among new findings with the capacity to gain clinical relevance is the detection of overexpressed snoRNAs known to regulate some critical cellular functions as ribosome biogenesis.Electronic supplementary materialThe online version of this article (10.1186/s12967-017-1370-x) contains supplementary material, which is available to authorized users.
ObjectivesThe study was aimed to determine the distribution of various breast cancer molecular subtypes in Saudi Arabia. Further, association between these subtypes and different epidemiological features was assessed.MethodsA retrospective study was conducted between January 2012 and December 2018, at the King Abdul Aziz University Hospital. A total of 740 cases of breast cancer, using immunohistochemistry, were classified into 4 major molecular subtypes: luminal A, luminal B, HER2-positive, and triple negative. Chi-squared test was performed to evaluate the relationship between these subtypes and clinico-pathological features.ResultsLuminal A (58.5%) subtype was the most prevalent, followed by triple negative (16%), luminal B (14%), and HER2-positive (11.5%). The average age of the patient at the time of diagnosis was found to be 49 years with an average tumor size of 3.2 cm. Out of all cases, 85% of cases were ductal, while 11.4% were lobular. 66.6% showed axillary lymph node metastases. While, 77% of lobular carcinomas were found almost exclusively in the luminal A and triple negative tumor subtype, 69.5% had modified radical mastectomy.ConclusionsLuminal A tumor was the most prevalent subtype, while HER2-positive was the least prevalent. Luminal A tumors were mostly associated with lobular carcinomas. HER2-positive and triple negative tumors showed higher histological grade and larger tumor size at the time of diagnosis. These tumors were commonly found in women below the age of 50 years. Carcinoma-in-situ was less prevalent in HER2-positive tumors. Furthermore, a strong association was observed between axillary lymph node status and molecular subtypes.
Background An anal fissure is one of the most common anorectal diseases resulting from a longitudinal tear in anoderm under the dentate line. It causes severe pain during defecation, and the resulting emotional stress leads to a reduction in the overall quality of life of a person. There are several medical and surgical treatment procedures that are employed to treat anal fissures. In the present retrospective study, we aimed to evaluate the safety and efficacy of lateral internal sphincterotomy (LIS) surgical procedure for the treatment of chronic anal fissure. Additionally, we also analyzed the complications arising after the surgery and the factors affecting the complications. Methods The present study is a retrospective study that included 691 patients treated for chronic anal fissure in a private sector setting, by a single Saudi female surgeon, starting from April 2004 to April 2020. Results Out of the 691 patients included in the study, all the patients were female, with an average age of 45.77 years (ranging from 17 to 82 years). Major complaints of the patients were as follows: pain, bleeding, constipation, pruritus, perianal discharge. Recurrence was reported in 2 patients (0.3%) while, 3 patients (0.4%) developed gas incontinence.The complaints of all patients with gas incontinence regressed over a period of time. Conclusion This study reports that lateral internal sphincterotomy (LIS) is a safe surgical treatment for chronic anal fissure, leading to a reduction in recurrence, incontinence rate and substantially improves symptoms, especially pain.
ObjectivesThe heterogenicity of breast cancer (BC) is determined by the status of human epidermal growth factor receptor 2 (HER2/neu), estrogen receptor (ER), and progesterone receptor (PR). Triple-positive BC (TPBC) expresses the amplification/overexpression of the HER2 pathway and is positive for ER and PR. This subtype has a distinct clinical behavior. However, very few studies are focused on TPBC. This study investigated the clinicopathological features and metastatic pattern of TPBC.MethodsA seven-year retrospective study was conducted at King Abdulaziz University Hospital in Jeddah, Kingdom of Saudi Arabia. All females with TPBC diagnosed between January 1, 2010, and June 30, 2017, were enrolled. Mean and standard deviation were calculated.ResultsFrom 1205 BC patients, the TPBC incidence was 10% (n = 124). The mean age at diagnosis was 51 years. On physical examination, a high tendency to show pathological skin changes was observed. Invasive ductal carcinoma was the most common histological type, presenting with a poorly differentiated histological grade (grade 3). Over a median two-year follow-up, the incidence of metastasis was 27.4% (n = 34). Bone was the most common site. The incidence of locoregional recurrence was 9.7%. Overall survival was 89.5%.ConclusionTPBC has an early tendency for metastasis and commonly affects the breast skin. BC should be approached based on the immunohistochemical diagnosis. We encourage more comprehensive studies to target TPBC for more insights into the heterogeneity of BC.
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