Breast cancer in an 18-year-old female: A fatal case report and literature review.

Breast cancer (BC) is the most frequent malignancy in both pre- and postmenopausal women. However, it is exceedingly rare in very young patients, and especially in adolescents. Herein, we report a case of an 18-year-old female diagnosed with invasive BC. The proband had been found to be negative for BC in close family members. A common BC genetic screening test for the Polish population did not detect any known founder mutations in the BRCA1 gene. Further evaluation identified a p.Ile157Thr (I157T) mutation in the CHEK2 gene, a p.Ala1991Val (A1991V) variant of unknown significance in the BRCA2 gene, p.Lys751Gln (K751Q) variant in the XPD (ERCC2) gene, and a homozygous p.Glu1008Ter (E1008*) mutation in the NOD2 gene. No other mutation had been found by next generation sequencing in major BC high-risk susceptibility genes BRCA1, BRCA2, as well as 92 other genes. To date, all these found alterations have been considered as low to moderate risk factors in the general population and moderate risk factors in younger women (<35 years of age). There are no previous articles relating low and moderate risk gene mutations to very young onset (below 20 years) BC with a fatal outcome. In our patient, a possible cumulative or synergistic risk effect for these 4 alterations, and a mutation in the NOD2 gene in particular, of which both presumably healthy parents were found to be carriers, is suggested.

The effect of penicillin administration in early life on murine gut microbiota and blood lymphocyte subsets.

BACKGROUND AND AIM: Antibiotics have many beneficial effects but their uncontrolled use may lead to increased risk of serious diseases in the future. Our hypothesis is that an early antibiotic exposition may affect immune system by altering gut microbiota. Therefore, the aim of the study was to determine the effect of penicillin treatment on gut microorganisms and immune system of mice. METHODS: 21-days old C57BL6/J/cmdb male mice were treated with low-dose of penicillin (study group) or water only (control group) for 4 weeks. Tissue and stool samples for histology or microbiome assessment and peripheral blood for CBC and flow cytometry evaluation were collected. RESULTS: We found high variability in microbiota composition at different taxonomic levels between littermate mice kept in the same conditions, independently of treatment regimen. Interestingly, low-dose of penicillin caused significant increase of Parabacteroides goldsteinii in stool and in colon tissue in comparison to control group (9.5% vs. 4.9%, p = 0.008 and 10.7% vs. 6.1%, p = 0.008, respectively). Moreover, mice treated with penicillin demonstrated significantly elevated percentage of B cells (median 10.5% vs 8.0%, p = 0.01) and decrease in the percentage of total CD4+ cell (median 75.4% vs 82.5%, p = 0.0039) with subsequent changes among subsets - increased percentage of regulatory T cells (Treg), T helper 1 (Th1) and T helper 2 (Th2) cells. CONCLUSION: Our study showed significant effect of penicillin on B and T cells in peripheral blood of young mice. This effect may be mediated through changes in gut microbiota represented by the expansion of Parabacteroides goldsteinii.

Selective gene expression profiling of mTOR-associated tumor suppressor and oncogenes in ovarian cancer.

The aim of this study was to selectively profile the activation status of mammalian target of rapamycin (mTOR)-associated oncogenes and tumor suppressor genes (TSGs) in ovarian cancer specimens, healthy ovaries and benign ovarian tumors, including endometrial cysts. We used a novel type of microfluidic gene array to examine the expression of 15 human tumor suppressors and oncogenes in ovarian cancer specimens of 53 patients, benign ovarian cysts of 29 women (endometrial and simple) and 11 healthy ovaries of individuals in whom the material was obtained during total hysterectomies performed because of fibroid changes. The array was custom-designed to include the following genes: NF1, RHEB, mTOR1, AKT-1, PTEN, TSC1, TSC2, KRAS, RPS6KB1, 4EBP1, TP53, EIF4E, STK11, PIK3CA and BECN1. Confirmatory immunohistochemical detection was performed for a group of selected proteins. Particularly significant differences were observed as to the expression of PTEN (p < 0.0001), TP53 (p = 0.0003), PIK3CA (p = 0.0003) and BECN1 (p = 0.0014) which were shown to be downregulated in cancer patients when compared to healthy ovaries and benign ovarian cysts (endometrial and simple). These markers did not show association with grade or stage of the tumor. Immunohistochemistry showed that PTEN, TP53, PIK3CA and BECN1 proteins are expressed in ovarian cancer. Our results indicate that there are significant differences in the expression of some of the mTOR-related tumor suppressors and oncogenes which could be associated with the pathogenesis of ovarian cancer.

The prognostic significance of the immunohistochemical expression of P53 and BCL-2 in endometrial cancer.

The objective of this study was to verify the frequency of P53 and BCL-2 immunohistochemical expression in 98 patients with endometrial carcinoma, and to correlate it with clinical stage and patient survival. A significant difference was found regarding the frequency of P53 expression when comparing type I and II tumors (23.7% and 54.5%, respectively; p = 0.006). A positive correlation was observed between P53 immunoexpression and patient survival in type I and II tumors (p = 0.009 and p = 0.036, respectively). BCL-2 expression was significantly more frequent in early clinical stages in both types of endometrial cancer (p 〈 0.001 and 0.002) and correlated with a decrease in overall survival in type I endometrial cancer (p = 0.014). Thus, the prognostic value of these biomarkers in endometrial cancer needs to be further investigated.

Prognostic significance of VEGF and its receptors in endometrioid endometrial cancer.

BACKGROUND: Angiogenesis is of crucial importance for endometrial tumor growth and Vascular Endothelial Growth Factor (VEGF) is the key mediator of angiogenesis. OBJECTIVE: The purpose of our study was to assess the prognostic value of VEGF and its receptors in relation to endometrioid endometrial carcinomas. MATERIAL AND METHODS: In this study we conducted an immunohistochemical evaluation of VEGF and VEGFRs expression in 84 tissue samples obtained from endometrioid endometrial cancer patients undergoing curative surgical treatment. RESULTS: Out of 84 cancers, strong positive expression of VEGF was seen in 35 (42%) tumors. The overall strong positive rates were 33% for VEGFR-1 and for 15% for VEGFR-2. There was a significant correlation between clinical stage and VEGF and VEGFR-1 overexpression (p=0.027 and p=0.004, respectively). Additionally there was a significant correlation between histological grade and VEGF and VEGFR-1 overexpression (p<0.001 and p<0.01, respectively). The 5-year DFS of patients with VEGF and VEGFR-1 overexpression was significantly lower than that of those with a weakly positive or negative tumor (p<0.001). CONCLUSION: Immunohistochemical evaluation of VEGF and VEGFR-1 overexpression may be a useful marker for predicting 5-year DFS in endometrioid endometrial cancer.

Prognostic significance of smac/DIABLO in endometrioid endometrial cancer.

Apoptosis may occur via a death receptor-dependent or independent (mitochondrial) pathway. The mitochondrial pathway is regulated by small molecules, such as smac/Diablo, which activates caspase cascades. This study examined smac/DIABLO expression in 76 patients with endometrioid endometrial cancers. Presence of smac/DIABLO was quantified by Western blot analysis using nonfixed fresh frozen tissues. Its appearance was found in 55 (72%) of examined tumors. Smac/DIABLO expression significantly correlated with tumor grade (p<0.001). Patients with positive smac/DIABLO tumors had a longer disease-specific survival when compared with those with negative tumors in the 10-year follow-up (p=0.043). The study demonstrated that negative smac/DIABLO expression was a poor prognostic sign.

Tumor necrosis factor-alpha and its receptors in epithelial ovarian cancer.

The aim of the present study was to characterize the expression pattern of tumor necrosis factor (TNF)-alpha and its receptors (TNF-Rs) in the epithelial ovarian cancer (EOC) and compare these results with the outcome of 126 patients. Presence of TNF-alpha, TNFR-1 and TNFR-2 were studied by Western blotting and immunohistochemistry. The proportion of samples positive for TNF-alpha and TNF-R2 was higher in epithelial ovarian cancer patients than in benign ovarian diseases (p<0.001 and p=0.016, respectively). Immunostaining intensity of TNF-R2 were correlated with tumor stage (p<0.001) and with reduced mean survival time (MST) (p=0.002). The results of the present study suggested that tissue expression of TNF-R2 in epithelial ovarian cancer was correlated with the highest risk of cancer progression. Thus, the clinical value of activated TNF system in epithelial ovarian cancer needs to be further investigated.

Neuroendocrine cells in the nasal mucosa - preliminary report.

UNLABELLED: The role of neuroendocrine cells (NC) in physiology and pathology of the human's respiratory tract is not fully understood. The aim of the study was the quantitative and morphometric assessment of NC in nasal mucosa in some pathological states. PATIENTS AND METHOD: 40 patients, aged 28-63 years, with clinical signs of chronic, hypertrophic rhinosinusitis were qualified for the study. Rhinitis chronica hypertrophica coexisted with aspirin triad or asthma in 10 patients (group I), with advanced obstructive sleep apnea syndrome (OSAS) in 10 patients (respiratory disturbance index, RDI>40, group II). Group III consisted of 10 patients with simple rhinitis chronica hypertrophica who habitually smoked cigarettes (at least 20 cigarettes a day) while 10 non-smoking patients with simple rhinitis chronica hypertrophica were qualified to the control group. Fragments of nasal mucosa of approximately 0.5 cm(2) were collected from medial or inferior turbinate during mucoplasty procedures. NC were detected immunohistochemically using antibodies against chromogranin A (DAKO). The microscopic sections were evaluated in the light microscopy. RESULTS: The study did not reveal the increased number of NC in examined fragments of nasal mucosa. Scattered NC were detected in single preparations of nasal mucous membrane in some patients in all groups. The number of detected neuroendocrine cells did not differ statistically between groups.