Background Streptococcus suis serotype 2 ( S. suis 2, SS2) is a major zoonotic pathogen that causes only sporadic cases of meningitis and sepsis in humans. Most if not all cases of Streptococcal toxic shock syndrome (STSS) that have been well-documented to date were associated with the non-SS2 group A streptococcus (GAS). However, a recent large-scale outbreak of SS2 in Sichuan Province, China, appeared to be caused by more invasive deep-tissue infection with STSS, characterized by acute high fever, vascular collapse, hypotension, shock, and multiple organ failure. Methods and FindingsWe investigated this outbreak of SS2 infections in both human and pigs, which took place from July to August, 2005, through clinical observation and laboratory experiments. Clinical and pathological characterization of the human patients revealed the hallmarks of typical STSS, which to date had only been associated with GAS infection. Retrospectively, we found that this outbreak was very similar to an earlier outbreak in Jiangsu Province, China, in 1998. We isolated and analyzed 37 bacterial strains from human specimens and eight from pig specimens of the recent outbreak, as well as three human isolates and two pig isolates from the 1998 outbreak we had kept in our laboratory. The bacterial isolates were examined using light microscopy observation, pig infection experiments, multiplex-PCR assay, as well as restriction fragment length polymorphisms (RFLP) and multiple sequence alignment analyses. Multiple lines of evidence confirmed that highly virulent strains of SS2 were the causative agents of both outbreaks.ConclusionsWe report, to our knowledge for the first time, two outbreaks of STSS caused by SS2, a non-GAS streptococcus. The 2005 outbreak was associated with 38 deaths out of 204 documented human cases; the 1998 outbreak with 14 deaths out of 25 reported human cases. Most of the fatal cases were characterized by STSS; some of them by meningitis or severe septicemia. The molecular mechanisms underlying these human STSS outbreaks in human beings remain unclear and an objective for further study.

The involvement of circulating microRNAs (miRNAs) in cancer and their potential as biomarkers of diagnosis and prognosis are becoming increasingly appreciated; however, little is known about circulating miRNA profiles in astrocytomas. In our study, we performed genome-wide serum miRNA analysis by the Solexa sequencing followed by validation conducted in the training and verification sets with a stem-loop quantitative reverse-transcription PCR (RT-qPCR) assay from serum samples of 122 untreated astrocytomas patients (WHO grades III-IV) and 123 normal controls. Identified miRNAs were subsequently examined in 55 grade II, 15 grade I astrocytomas, 11 astrogliosis, 42 other primary brain tumors and 8 tumor tissues from grades II-IV astrocytomas. In addition, paired serum samples before and after operation were collected from 14 malignant astrocytomas to determine the effect of surgery on the miRNAs' levels. A marked difference in serum miRNA profile was observed between high-grade astrocytomas and normal controls. Seven miRNAs were validated by RT-qPCR assay to be significantly decreased in grades II-IV patients (p < 0.001), including miR-15b * , miR-23a, miR-133a, miR-150 * , miR-197, miR-497 and miR-548b-5p, and the seven-miRNA panel demonstrated a high sensitivity (88.00%) and specificity (97.87%) for malignant astrocytomas prediction. These identified miRNAs also exhibited a global decrease in tumor tissues relative to normal tissues. Furthermore, these miRNAs in serum were markedly elevated after operation (p < 0.001). In addition, some of these serum miRNAs were significantly different between malignant and benign cases, astrogliosis and other primary brain tumors. The seven serum miRNAs identified in our study hold potential as noninvasive biomarker for malignant astrocytomas.Astrocytomas are the most common primary brain tumors arising from astrocytes, the most abundant type of glial cells of the central nervous system or, more likely, from resident cancer stem cells. Based on their histology and morphological features, astrocytomas are divided into four clinical grades 1 : Grade I (including pilocytic astrocytomas and subependymal giant cell astrocytoma) comprises slowly growing benign astrocytomas, grade II (diffuse astrocytomas and pleomorphic xanthoastrocytoma) represents the least malignant cases and grades III (anaplastic astrocytomas) and IV (glioblastomas or GBM) are highly malignant and have some of the worst survival rates of all human cancers. 1,2 Grade II tumors have an inherent tendency to spontaneously progress to grades III or secondary IV. 1 Surgery followed by chemoradiotherapy is the mainstream of primary grade IV astrocytomas treatment. In the course of postradiation events, however, it is sometimes difficult for neurosurgeons, radiologists and pathologists to discriminate tumor recurrence from radiation necrosis which usually results in astrogliosis. 3,4 Despite the recent advances in therapeutic strategies, such as surgical resection and adjuvant radiotherapy and chemotherapy, the 5-year ...

Both Xp11 translocation renal cell carcinomas and the corresponding mesenchymal neoplasms are characterized by a variety of gene fusions involving TFE3. It has been known that tumors with different gene fusions may have different clinicopathologic features; however, further in-depth investigations of subtyping Xp11 translocation-associated cancers are needed in order to explore more meaningful clinicopathologic correlations. A total of 22 unusual cases of Xp11 translocation-associated cancers were selected for the current study; 20 cases were further analyzed by RNA sequencing to explore their TFE3 gene fusion partners. RNA sequencing identified 17 of 20 cases (85%) with TFE3-associated gene fusions, including 4 ASPSCR1/ASPL-TFE3, 3 PRCC-TFE3, 3 SFPQ/PSF-TFE3, 1 NONO-TFE3, 4 MED15-TFE3, 1 MATR3-TFE3, and 1 FUBP1-TFE3. The results have been verified by fusion fluorescence in situ hybridization (FISH) assays or reverse transcriptase polymerase chain reaction (RT-PCR). The remaining 2 cases with specific pathologic features highly suggestive of MED15-TFE3 renal cell carcinoma were identified by fusion FISH assay. We provide the detailed morphologic and immunophenotypic description of the MED15-TFE3 renal cell carcinomas, which frequently demonstrate extensively cystic architecture, similar to multilocular cystic renal neoplasm of low malignant potential, and expressed cathepsin K and melanotic biomarker Melan A. This is the first time to correlate the MED15-TFE3 renal cell carcinoma with specific clinicopathologic features. We also report the first case of the corresponding mesenchymal neoplasm with MED15-TFE3 gene fusion. Additional novel TFE3 gene fusion partners, MATR3 and FUBP1, were identified. Cases with ASPSCR1-TFE3, SFPQ-TFE3, PRCC-TFE3, and NONO-TFE3 gene fusion showed a wide variability in morphologic features, including invasive tubulopapillary pattern simulating collecting duct carcinoma, extensive calcification and ossification, and overlapping and high columnar cells with nuclear grooves mimicking tall cell variant of papillary thyroid carcinoma. Furthermore, we respectively evaluated the ability of TFE3 immunohistochemistry, TFE3 FISH, RT-PCR, and RNA sequencing to subclassify Xp11 translocation-associated cancers. In summary, our study expands the list of TFE3 gene fusion partners and the clinicopathologic features of Xp11 translocation-associated cancers, and highlights the importance of subtyping Xp11 translocation-associated cancers combining morphology, immunohistochemistry, and multiple molecular techniques.

Circulating microRNAs (miRNAs) are emerging as clinically useful tools for cancer detection; however, little is known about their early diagnostic impact on RCC. The levels of 754 serum miRNAs were initially determined using a TaqMan Low Density Array in two pooled samples from 25 RCC and 25 noncancer controls. Markedly dysregulated miRNAs in RCC cases were subsequently validated individually by qRT-PCR in another 107 patients and 107 controls arranged in two sets. The serum levels of miR-193a-3p, miR-362 and miR-572 were significantly increased whereas the levels of miR-28-5p and miR-378 were markedly decreased in patients with RCC, even in those with stage I disease, compared with the noncancer controls (P < 0.01). The areas under the ROC curve (AUCs) for the 5 combined miRNAs were 0.807 (95% CI, 0.687–0.928) and 0.796 (95% CI, 0.724–0.867) for the training set and the validation set, respectively. Furthermore, the panel enabled the differentiation of stage I RCC from controls with AUC of 0.807 (95% CI, 0.731–0.871), a sensitivity of 80% and a specificity of 71%. This panel of 5 serum miRNA may have the potential to be used clinically as an auxiliary diagnostic tool for the early detection of RCC.

An increasing number of TFE3 rearrangement-associated tumors, such as TFE3 rearrangement-associated perivascular epithelioid cell tumors (PEComas), melanotic Xp11 translocation renal cancers, and melanotic Xp11 neoplasms, have recently been reported. We examined 12 such cases, including 5 TFE3 rearrangement-associated PEComas located in the pancreas, cervix, or pelvis and 7 melanotic Xp11 translocation renal cancers, using clinicopathologic, immunohistochemical, and molecular analyses. All the tumors shared a similar morphology, including a purely nested or sheet-like architecture separated by a delicate vascular network, purely epithelioid cells displaying a clear or granular eosinophilic cytoplasm, a lack of papillary structures and spindle cell or fat components, uniform round or oval nuclei containing small visible nucleoli, and, in most cases (11/12), melanin pigmentation. The levels of mitotic activity and necrosis varied. All 12 cases displayed moderately (2+) or strongly (3+) positive immunoreactivity for TFE3 and cathepsin K. One case labeled focally for HMB45 and Melan-A, whereas the others typically labeled moderately (2+) or strongly (3+) for 1 of these markers. None of the cases were immunoreactive for smooth muscle actin, desmin, CKpan, S100, or PAX8. PSF-TFE3 fusion genes were confirmed by reverse transcription polymerase chain reaction in cases (7/7) in which a novel PSF-TFE3 fusion point was identified. All of the cases displayed TFE3 rearrangement associated with Xp11 translocation. Furthermore, we developed a PSF-TFE3 fusion fluorescence in situ hybridization assay for the detection of the PSF-TFE3 fusion gene and detected it in all 12 cases. Clinical follow-up data were available for 7 patients. Three patients died, and 2 patients (cases 1 and 3) remained alive with no evidence of disease after initial resection. Case 2 experienced recurrence and remained alive with disease. Case 5, a recent case, remained alive with extensive abdominal cavity metastases. Our data suggest that these tumors belong to a single clinicopathologic spectrum and expand the known characteristics of TFE3 rearrangement-associated tumors.

To evaluate the diagnostic accuracy of computed tomography (CT)-guided percutaneous lung biopsy for solitary pulmonary nodules. Three hundred and eleven patients (211 males and 100 females), with a mean age of 59.6 years (range, 19–87 years), who were diagnosed with solitary pulmonary nodules and underwent CT-guided percutaneous transthoracic needle biopsy between January 2008 and January 2014 were reviewed. All patients were confirmed by surgery or the clinical course. The overall diagnostic accuracy and incidence of complications were calculated, and the factors influencing these were statistically evaluated and compared. Specimens were successfully obtained from all 311 patients. A total of 217 and 94 cases were found to be malignant and benign lesions, respectively, by biopsy. Two hundred and twenty-five (72.3%) carcinomas, 78 (25.1%) benign lesions, and 8 (2.6%) inconclusive lesions were confirmed by surgery and the clinical course. The diagnostic accuracy, sensitivity, and specificity of CT-guided percutaneous transthoracic needle biopsy were 92.9%, 95.3%, and 95.7%, respectively. The incidences of pneumothorax and self-limiting bleeding were 17.7% and 11.6%, respectively. Taking account of all evidence, CT-guided percutaneous lung biopsy for solitary pulmonary nodules is an efficient, and safe diagnostic method associated with few complications.

miR-195, one of the miR-16/15/195/424/497 family members, has been shown to play an important role in tumorigenesis, as a tumor suppressor. Here, we assess miR-195 expression in colorectal cancer, which has not been investigated before, and its clinical significance including survival analysis. The in vivo significance of expression of miR-16/15/195/424/497 in matched normal and tumor tissues of colorectal cancers was evaluated using a quantitative real-time RT-PCR. Two colorectal cancer cell lines and 85 colorectal cancer and paired normal patient samples with detailed clinical follow-up information were selected. The statistical significance of these markers for disease prognosis was evaluated using a two-tailed, paired Wilcoxon test. A Kaplan-Meier survival curve was generated following a logrank test. As a result, miR-424 was significantly over-expressed, while miR-15a, miR-15b, miR-16, and miR-195 were downregulated in tumors compared with normal colorectal samples (all P < 0.01). Reduced expression of miR-195 occurred more often in patients with lymph node metastasis and advanced tumor stage (all P < 0.01). Kaplan-Meier survival analysis indicated that patients with reduced miR-195 had a poor overall survival (P < 0.01). Moreover, the multivariate analysis showed that reduced expression of miR-195 was an independent predictor of overall survival. Our data indicate the potential of miR-195 as a novel diagnostic or prognostic biomarker for CRC.

Background and AimCirculating microRNAs (miRNAs) are potential biomarkers for cancer detection; however, little is known about their prognostic impact on oesophageal squamous cell carcinoma (ESCC). The current study aims to uncover novel miRNAs for prognostic biomarkers in ESCC patients.Patients and MethodsWe initially screened the expression of 754 serum miRNAs using TaqMan Low Density Array in two pooled samples respectively from 28 ESCC and 28 normal controls. Markedly upregulated miRNAs in ESCC and some miRNAs reported to be differently expressed in ESCC tissue were then validated individually by RT-qPCR in another 83 patients and 83 controls arranged in two phases. The changes of the selected miRNAs during the esophagectomy and their prognostic value were examined.ResultsSeven serum miRNAs were found to be significantly higher in ESCC than in controls; namely, miR-25, miR-100, miR-193-3p, miR-194, miR-223, miR-337-5p and miR-483-5p (P<0.0001), and the area under the receiver-operating-characteristic (ROC) curve (AUC) for the seven-miRNA panel was 0.83 (95% CI 0.75–0.90). Most of these miRNAs declined markedly in postoperative samples versus preoperative samples (P<0.05). Moreover, high level of miR-25 was significantly correlated with shorter overall survival in patients (P = 0.027). Cox regression analysis identified lymph node metastasis, miR-25 and miR-100 as the independent risk factors for overall survival (hazard ratio (HR) 2.98 [1.36–6.55], P = 0.006; HR 3.84 [1.02–14.41], P = 0.029; HR 4.18 [1.21–14.50], P = 0.024, respectively).ConclusionThe seven serum miRNAs could potentially serve as novel biomarkers for ESCC; moreover, specific miRNAs such as miR-25 and miR-100 can predict poor survival in ESCC.