Overexpression of FRAT1 protein is closely related to triple-negative breast cancer.

Purpose: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a poor prognosis and a lack of targeted therapy. Overexpression of FRAT1 is thought to be associated with this aggressive subtype of cancer. Here, we performed a comprehensive analysis and assessed the association between overexpression of FRAT1 and TNBC. Methods: First, using different web-based bioinformatics platforms (TIMER 2.0, UALCAN, and GEPIA 2), the expression of FRAT1 was assessed. Then, the expression of the FRAT1 protein and hormone receptors and HER2 status were assessed by immunohistochemical analysis. For samples of tumors with equivocal immunoreactivity, we performed silver in situ hybridization of the HER2 gene to determine an accurate HER2 status. Next, we used the R package and bc-GenExMiner 4.8 to analyze the relationship between FRAT1 expression and clinicopathological parameters in breast cancer patients. Finally, we determined the relationship between FRAT1 overexpression and prognosis in patients. Results: The expression of FRAT1 in breast cancer tissues is significantly higher than in normal tissue. FRAT1 expression was significantly related to worse overall survival (P < 0.05) and was correlated with these clinicopathological features: T stage, N stage, age, high histologic grade, estrogen receptor status, progesterone receptor status, Her-2 status, TNBC status, basal-like status, CK5/6 status, and Ki67 status. Conclusion: FRAT1 was overexpressed in breast cancer compared to normal tissue, and it may be involved in the progression of breast cancer malignancy. This study provides suggestive evidence of the prognostic role of FRAT1 in breast cancer and the therapeutic target for TNBC.

Metastatic Intracranial Hemangiopericytoma to the Spinal Column: A Case Report.

Intracranial hemangiopericytoma (HPC) is a rare brain tumor with aggressive biologic behavior associated with high recurrence rate and often with extracranial metastasis. The most common sites of extracranial metastasis of the intracranial HPC are the long bones, lung, liver and abdominal cavity in the order of frequencies. Extracranial metastases usually occur long after the initial diagnosis of the primary tumor. Metastatic intracranial HPC to the vertebra has been rarely reported. We present a case of intracranial HPC metastasized to the L2 vertebral body 13 years after multiple surgical resections and radiotherapy of the primary intracranial HPC.

Effect of low-dose valsartan on proteinuria in normotensive immunoglobulin A nephropathy with minimal proteinuria: a randomized trial.

BACKGROUND/AIMS: Immunoglobulin A nephropathy (IgAN) is a generally progressive disease, even in patients with favorable prognostic features. In this study, we aimed to investigate the antiproteinuric effect and tolerability of low-dose valsartan (an angiotensin II receptor blocker) therapy in normotensive IgAN patients with minimal proteinuria of less than 0.5 to 1.0 g/day. METHODS: Normotensive IgAN patients, who had persistent proteinuria with a spot urine protein-to-creatinine ratio of 0.3 to 1.0 mg/mg creatinine, were recruited from five hospitals and randomly assigned to either 40 mg of valsartan as the low-dose group or 80 mg of valsartan as the regular-dose group. Clinical and laboratory data were collected at baseline, and at 4, 8, 12, and 24 weeks after valsartan therapy. RESULTS: Forty-three patients (low-dose group, n = 23; regular-dose group, n = 20) were enrolled in the study. Proteinuria decreased significantly not only in the regular-dose group but also in the low-dose group. The change in urine protein-to-creatinine ratio at week 24 was -41.3% ± 26.1% (p < 0.001) in the regular-dose group and -21.1% ± 45.1% (p = 0.005) in the low-dose group. In the low-dose group, blood pressure was constant throughout the study period, and there was no symptomatic hypotension. In the regular-dose group, blood pressure decreased at weeks 8 and 12. No significant change in glomerular filtration rate, serum creatinine level, or serum potassium level was observed during the study period. CONCLUSIONS: Our results suggest that low-dose valsartan can significantly reduce proteinuria without causing any intolerability in normotensive IgAN patients with minimal proteinuria.

Primary intracranial fibrosarcoma presenting with hemorrhage.

Primary intracranial fibrosarcomas (PIFs) are extremely rare and the origin of these tumors is still controversial. The rarity of primary intracranial fibrosarcomas makes it difficult to diagnose them correctly and establish a standard treatment. The pathologic diagnosis is made by distinguishing findings from light microscopic and immunohistochemistry analysis. PIFs have been known to be very aggressive neoplasms. The extra-axial location of the tumor could provide an opportunity to perform a total resection even if it does not mean a cure. We present a case of PIFs mimicking a falx meningioma in a 17-year-old man.

Extremely delayed brain metastasis from renal cell carcinoma.

Brain metastasis occurs in 3.9-24% of patients with renal cell carcinoma (RCC), with an average interval from nephrectomy to brain metastasis of 1 to 3 years. A few cases have been reported where brain metastasis occurred after a delay of more than 10 years from the initial onset of renal cell carcinoma. This long interval for central nervous system metastasis from the primary cancer has been recognized as an indicator of better prognosis. Histopathological confirmation and aggressive treatment must be considered in these delayed brain metastases cases, since the patients usually show long survival and good prognosis. We present a case of a 76-year-old woman who developed extremely late multiple brain metastases 18 years after a nephrectomy for RCC.

Osteochondroma of the calcaneus presenting as Haglund's deformity.

Haglund's deformity is a symptomatic osseous prominence of the posterosuperior corner of the calcaneus creating posterior heel pain and swelling around the insertion of the Achilles tendon. We have experienced an exceptionally huge Haglund's deformity in a 22-year-old female who initially presented to us with a large painful bony heel mass that had developed over the last decade. We performed the surgical resection of the prominence and the pathology confirmed the diagnosis of calcaneal osteochondroma. To our best knowledge, such a gigantic Haglund's deformity caused by calcaneal osteochondroma has never been reported in any medical literature.

mtDNA mutations increase tumorigenicity in prostate cancer.

Mutations in the mtDNA have been found to fulfill all of the criteria expected for pathogenic mutations causing prostate cancer. Focusing on the cytochrome oxidase subunit I (COI) gene, we found that 11-12% of all prostate cancer patients harbored COI mutations that altered conserved amino acids (mean conservation index=83%), whereas <2% of no-cancer controls and 7.8% of the general population had COI mutations, the latter altering less conserved amino acids (conservation index=71%). Four conserved prostate cancer COI mutations were found in multiple independent patients on different mtDNA backgrounds. Three other tumors contained heteroplasmic COI mutations, one of which created a stop codon. This latter tumor also contained a germ-line ATP6 mutation. Thus, both germ-line and somatic mtDNA mutations contribute to prostate cancer. Many tumors have been found to produce increased reactive oxygen species (ROS), and mtDNA mutations that inhibit oxidative phosphorylation can increase ROS production and thus contribute to tumorigenicity. To determine whether mutant tumors had increased ROS and tumor growth rates, we introduced the pathogenic mtDNA ATP6 T8993G mutation into the PC3 prostate cancer cell line through cybrid transfer and tested for tumor growth in nude mice. The resulting mutant (T8993G) cybrids were found to generate tumors that were 7 times larger than the wild-type (T8993T) cybrids, whereas the wild-type cybrids barely grew in the mice. The mutant tumors also generated significantly more ROS. Therefore, mtDNA mutations do play an important role in the etiology of prostate cancer.

Comparison of clinicopathologic characteristics and genetic alterations between microsatellite instability-positive and microsatellite instability-negative sporadic colorectal carcinomas in patients younger than 40 years old.

PURPOSE: Many studies have demonstrated that sporadic microsatellite instability-positive colorectal cancers share several clinicopathologic features with hereditary nonpolyposis colorectal cancers, including right-sided location, young age of onset, characteristic histomorphologic features, and a good prognosis. The aim of this study was to define distinct clinicopathologic features of sporadic microsatellite instability-positive colorectal cancers and to compare genotypic characteristics between microsatellite instability-positive and microsatellite instability-negative colorectal cancers in a young group. METHODS: We analyzed 61 cases of young patients (<40 years old) with colorectal cancers for microsatellite instability at five mononucleotide and three dinucleotide repeats, loss of heterozygosity at APC and DCC, and K-ras and p53 mutations. Microsatellite instability status was correlated with molecular genetic factors and clinicopathologic parameters. RESULTS: Microsatellite instability positivity was detected in 19 (31.1 percent) of 61 cases. Allelic alterations in TGFbetaRII, BAX, and IGFIIR were observed exclusively in microsatellite instability-positive tumors (63.1, 26.3, and 26.3 percent, respectively). Microsatellite instability-positive tumors exhibited a lower frequency of the p53 mutation (10.5 percent) than microsatellite instability-negative tumors (47.6 percent; P < 0.05). However, microsatellite instability status was not associated with APC or DCC allelic deletion or with the K-ras mutation. Microsatellite instability-positive colorectal cancers exhibited a proclivity toward proximal location, expansive growth pattern, and large tumor size (P < 0.05). Microsatellite instability-positive colorectal cancers had lower preoperative serum carcinoembryonic antigen levels (P < 0.05), a less advanced stage at presentation (P < 0.05), and a tendency toward better prognosis (P = 0.051) than microsatellite instability-negative colorectal cancers. However, there was no difference between microsatellite instability-positive and microsatellite instability-negative colorectal cancers regarding gross features, tumor grade, and extracellular mucin production. CONCLUSION: These results suggest that sporadic microsatellite instability-positive colorectal cancers in young patients have different histomorphologic features from microsatellite instability-negative colorectal cancers and hereditary nonpolyposis colorectal cancers, some overlap of genetic alterations on multistep carcinogenesis with microsatellite instability-negative colorectal cancers, and a tendency for better prognosis.