Objective To investigate the expression of hypoxia inducible factor 1α (HIF-1α) and glucose transporter 1 (GLUT1) in lung adenocarcinoma and its correlation with tumor metastasis. Methods SP immunohistochemistry was used to detect GLUT1 and HIF-1α protein expression in 125 lung adenocarcinoma, including 41 cases without metastasis, 38 cases with lymphatic metastasis and 46 cases with brain metastasis. The correlation of GLUT1 and HIF-1α in lung adenocarcinoma metastasis was analyzed by using x 2 test and Pearson correlation analysis. Results Most lung adenocarcinoma were histologically heterogeneous, which contained more than one adenocarcinoma type. 73.2 % (30/41) cases were acinar predominant adenocarcinoma in lung adenocarcinoma without metastasis; 53.6 % (15/38) cases were acinar predominant adenocarcinoma and 26.3 % (10/38) cases were solid predominant adenocarcinoma in lung adenocarcinoma with lymphatic metastasis; 47.8 % (22/46) cases were papillary predominant adenocarcinoma and 34.8 % (16/46) cases were solid predominant adenocarcinoma in lung adenocarcinoma with brain metastases. The expression level of GLUT1 and HIF-1α in lung adenocarcinoma with lymphatic metastasis group was higher than that of the group without tumor metastasis (P< 0.05); the expression of GLUT1 and HIF-1α were positively correlated (r=0.407, P=0.000). Conclusions Papillary adenocarcinoma is the most histological type in lung adenocarcinoma with brain metastasis, suggesting that papillary adenocarcinoma is more prone to brain metastasis. The expression of GLUT1 and HIF-1α play an important role in lymph node metastasis and brain metastasis of lung adenocarcinoma.

Objective To evaluate the diagnostic value of gray-scale ultrasonography (GSU) combined with contrast-enhanced ultrasonography (CEUS) and real-time elastography imaging (EI) in solid thyroid nodules.Methods A total of 124 solid nodules were collected from Xuanwu Hospital of Capital Medical University from September 2011 to November 2014, including 49 benign nodules and 75 malignant nodules conifrmed by surgical pathology. The data of multimodal imaging were retrospectively analyzed and compared with the pathological results. The parameters among the groups were compared byχ2 test. Four diagnostic models including the statistically signiifcant independent variables were established accord to different combinations of routine ultrasound examination. The binary Logistic regression equation using the pathological results as the dependent variable Y and the ultrasound features of thyroid nodules as independent variableX was established for calculating the area under the receiver operator curve (ROC) and multiple regression analysis furthermore.Results There were statistically significant differences in aspect ratio, margin condition, echo type, CEUS features, elastic imaging score and elastic strain rate of benign and malignant thyroid nodules(χ2=13.966, 7.106, 24.215, 17.250 and 27.158,P<0.05).The four Logistic regression models were statistically signiifcant (χ2=5.37, 5.37, 8.155, 8.155, allP<0.05). By using modelⅠ,Ⅱ,Ⅲ andⅣ, the diagnostic sensitivity, speciifcity and accuracy of malignant nodules were (73.8%, 75.9%, 79.7%, 83.3%), (67.5%, 70.7%, 85.2%, 86.7%), and (71.8%, 74.2% 81.8%, 84.4%) respectively. The area under the ROC of logistic equation predicted values were (0.778, 0.809, 0.875 and 0.898, allP<0.01). Multivariate categorical analysis showed that aspect ratio, margin condition and the elastic strain rate ratio (χ2=13.73, 7.541 and 11.461, allP<0.05) of thyroid nodules were effective diagnostic indicators. Conclusions Our study indicated that CEUS and EI could be helpful modality for GSU to improve the diagnostic accuracy of thyroid nodules. The combined application of multi mode ultrasound examination has a high diagnostic value.

Objective To assess the diagnostic value of contrast enhanced ultrasound (CEUS),elastography and their combined use in diagnosing thyroid nodules of thyroid imaging reporting and data system (TI-RADS) 4. Methods From November 2011 to August 2016, 159 TI-RADS 4 nodules diagnosed by conventional ultrasound were prospectively enrolled and examined by CEUS and elastography before surgery. Multivariate logistic regression models were established for CEUS and CEUS combined with elastography to diagnose thyroid malignancy. The diagnostic performances of CEUS, elastography and their combined use were evaluated with the receiver operating characteristic (ROC) curve. The sensitivity,specificity, accuracy, positive predictive value, negative predictive value and omission diagnostic rate of CEUS, elastography and their combined use were compared by Chi-square test. Results The CEUS features significantly predicting malignancy were heterogeneous enhancement, hypoenhancement, without or incomplete ring-enhancement and later time to peak than the surrounding parenchyma (χ2=24.378, 69.194,29.434 and 7.375, all P < 0.01). Furthermore, the multivariate logistic regression for CEUS combined with elastography showed that heterogeneous enhancement, ring enhancement and elasticity score were the independent predictors of thyroid malignancy. The area under the ROC curve of CEUS combined with elastography was (0.921±0.023) which was higher than that of CEUS and elatography (0.88±0.029 and 0.80±0.038, respectively; both P < 0.05). Moreover, the sensitivity, accuracy and negative predictive value of CEUS combined with elastography were 92.1%, 86.2% and 84.6%, respectively. The omission diagnostic rate of CEUS combined with elastography (7.9%) was reduced. And the diagnostic accuracy of CEUS combined with elastography was significantly higher than that of CEUS and elastography (P < 0.05). While the diagnostic accuracy of CEUS was close to the elastography, the difference was not statistically significant (P > 0.05). Conclusion The diagnostic value of CEUS combined with elastography was remarkably significant in the differential diagnosis of TI-RADS 4 nodules.

Objective: To study the expression and mechanism of long-chain non-coding RNA PVT1 in tumor by bioinformatics analysis and experimental verification, and to provide new ideas for the study of the pathogenesis of tumors. Methods: The expression of PVT1 in 14 common tumors was downloaded from starBase v2.0 public database, which also was verified by PVT1 RNA-in situ hybridization.The upstream transcription factors, the downstream target microRNA(miRNA) for PVT1 and the target genes for the target miRNAs were predicted and analyzed by using bioinformatics based on the database of UCSC Genome Browser, HMDD v2.0, miRTar Base, JASPAR databases. Results: StarBase database analysis and RNA in situ hybridization showed that PVT1 was highly expressed in kidney clear cell carcinoma and colon and rectal adenocarcinoma. PVT1 was regulated by the upstream transcription factors CREB1, Atf1, SP1, KLF5, STAT3, while it could control the expression of the downstream target miR-16. bcl-2, VEGFA, CCNE1, CCND1 and SHOC2 showed an interaction with the transcription factor of PVT1, which formed a feedback regulatory pathway. Conclusions PVT1 is highly expressed in kidney clear cell carcinoma and colon and rectal adenocarcinoma.The predictive analysis of bioinformatics demonstrates that transcription factor/PVT1/miR-16/target gene signal axon may be an important molecular mechanism, which provide a valuable clue for further functional mechanism research of long-chain non-coding RNA.

OBJECTIVETo study the expression and prognostic significance of ERG and SPINK1 expression in endocrine-treated prostatic cancer.

METHODSProstatic needle biopsies from 118 prostatic cancer patients primarily treated with endocrine therapy were reviewed. Immunohistochemical study for ERG and SPINK1 protein was carried out.

RESULTSCo-expression of ERG and SPINK1 was not observed. The frequency of ERG protein expression in the 118 biopsies studied was 9.3% (11/118). The positive expression correlated with T stage (P=0.04) but not with patient age at diagnosis, prostatic specific antigen level, Gleason's score, M stage, tumor area and progression-free survival. Positive expression of SPINK1 was demonstrated in 11.0% (13/118) of the biopsies. SPINK1-positive cases carried a significantly shorter progression-free survival, as compared with SPINK1-negative cases (P=0.022). The expression was not associated with any other clinicopathologic variables. The following expression pattern showed statistically significant correlation with the clinical progress (P=0.029): ERG+/SPINK1- (11/118, 9.3%), ERG-/SPINK1+ (13/118, 11.0%) and ERG-/SPINK1- (94/118, 79.7%).

CONCLUSIONSERG and SPINK1 proteins are mutually exclusive.SPINK1 expression is associated with more aggressive clinical behavior and can serve as a prognostic biomarker in prostatic cancer.

Aged ; Aged, 80 and over ; Antineoplastic Agents, Hormonal ; therapeutic use ; Carrier Proteins ; metabolism ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; Prostatic Neoplasms ; drug therapy ; metabolism ; pathology ; Trans-Activators ; metabolism ; Transcriptional Regulator ERG ; Trypsin Inhibitor, Kazal Pancreatic

OBJECTIVE: Although rare, invasive rhino-orbital-skull base aspergillosis usually is fatal and necessitates prompt diagnosis, surgical intervention and antifungal treatment. METHOD: A case series of 5 patients, with review of treatments and outcomes. RESULT: Five patients initially presented with orbital apex syndrome without apparent rhino-sinus disease. Histologic examination revealed invasive aspergillosis. Four patients underwent transnasal endoscopic surgical exploration of rhino-orbital-skull base, and three of them simultaneously underwent optic nerve decompression. One patient underwent the rhinopharyngeal biopsy. Following surgical debridement and antifungal drug, Two patients achieved various degree of recovery, 1 patient (case 5) showed vision improvement, from counting fingers to 0.1 and symptom-free during 65 months follow-up. One patient (case 1) showed no recovery of vision from no light perception, but symptom-free during 43 months follow-up. Other three patients respectively died of massive intracranial spread (case 3), postoperative brainstem hemorrhage (case 2) and sepsis (case 4). CONCLUSION Invasive sino-orbital-skull base aspergillosis often may resemble inflammatory conditions. Early diagnosis and surgical intervention are required to improve vision and survival. The endoscopic surgical exploration and biopsy often are necessary to rule out fungal sinus infection before considering steroid use, especially in immunocompromised individuals. The patients with invasive rhino-orbital-skull base aspergillosis usually have a poor prognosis.
Adult ; Aged ; Aspergillosis ; pathology ; Female ; Humans ; Male ; Middle Aged ; Orbit ; microbiology ; Orbital Diseases ; etiology ; metabolism ; Retrospective Studies ; Sinusitis ; microbiology ; Skull Base ; microbiology

Objective:To investigate the clinicopathological and molecular genetic characteristics of tall cell variant and hobnail variant of papillary thyroid carcinoma (PTC).Methods:Twenty-one cases of tall cell variant (TCV-PTC) of PTC (TCV-PTC) and ten cases of hobnail variant of PTC (HV-PTC), as the highly aggressive group, were collected from Xuanwu Hospital from August 2009 to August 2015. Twenty-two cases of follicular variant and 21 classical PTC cases were included as control. Relevant clinical and pathologic data were obtained, and in some cases, paraffin samples were selected for gene mutation spectrum analysis using second generation sequencing.Results:There were 18 males and 56 females; 57 patients were younger than 55 years of age, and 17 patients were 55 years or older. The mean tumor size was 1.6 cm for the high-aggressive group (TCV-PTC and HV-PTC), 1.1 cm for the follicular subtype, and 1.6 cm for the classical type. There were 54 cases with thyroid capsule invasion, 24 cases with extra-thyroidal invasion, and 45 patients with lymph node metastases. Regional recurrence occurred in 7 cases, no recurrence in 54 cases, and 13 patients were lost to follow-up. The highly aggressive group was more likely to show extra-thyroidal invasion, lymph node metastases and recurrence than those with classical PTC ( P<0.05). Within this cohort, BRAF V600E mutation was detected in 53 cases and TERT promoter mutation in 6 cases. Compared with the single mutation group and no mutation group, BRAF and TERT promoter co-mutation group was more commonly detected in older age, male, larger tumor size and more prone to extra-thyroid invasion ( P<0.05). In addition, among BRAF and TERT co-mutation cases, the highly-aggressive group accounted for the highest proportion (5/6). Conclusions:TCV-PTC and HV-PTC, as highly-aggressive variants of PTC, show more aggressive biologic behavior (more lymph node metastasis, external thyroid invasion and recurrences) than the classical and follicular variants of PTC. Coexisting BRAF and TERT promoter mutations may be associated with invasive biologic behavior.

Objective To investigate the clinicopathological significance of BRAF V600E and CTNNB1 gene mutations in adamantinomatous craniopharyngiomas (ACP) and papillary craniopharyngiomas (PCP). Methods The retrospective study included a total of 67 craniopharyngiomas diagnosed from October 2009 to August 2018 at Xuanwu Hospital, Capital Medical University. The immunohistochemical staining for β?catenin and BRAF V600E expression, Sanger sequencing of exon 3 of CTNNB1, BRAF mutation analysis by scorpions amplification refractory mutation system (ARMS) fluorescence quantitative PCR were performed. Univariate survival analysis was used to correlate with tumor recurrence. Results Of the 67 patients, 53 were ACPs and 14 were PCPs. Four patients underwent multiple operations and one of them presented with malignant transformation into squamous cell carcinoma. Histologically, ACPs were characterized by whorl?like cell clusters, peripheral palisaded layer, stellate reticulum, finger?shaped protrusions, ghost cells and wet keratinous substances. While PCPs usually consisted of mature squamous epithelium associated with fibrovascular stroma resulting in papillary appearance. The nuclear immunopositivity for β?catenin was observed in 73.6% (39/53) of ACPs, and it was absent in PCPs (0/14). The nuclear translocation of β?catenin usually presented at whorl?like structures or around ghost cells. Of all the cases, mutations analysis in exon 3 of β?catenin gene CTNNB1 were successful in 46 cases and 42.1% (16/38) of ACP showed CTNNB1 gene mutation, while none of the PCPs harbored CTNNB1 gene mutation (0/8). The cytoplasmic immunopositivity for BRAF V600E mutant protein was found in all PCPs (14/14) and negative in all ACPs (0/53). ARMS?PCR results showed that BRAF V600E mutations were observed in 13/14 of PCPs but not seen in ACPs (0/53). Follow?up data were available in 35 patients with duration of 2 to 120 months. Ten patients experienced recurrences after the first surgery. Upon univariate survival analysis, only subtotal excision was found to be associated with increased recurrence (P=0.032), while pathological type, postoperative radiotherapy and CTNNB1 gene mutation were not (P>0.05). Conclusions There is significant difference in the expression of BRAF V600E and CTNNB1 genes between ACP and PCP, and their immunohistochemical and molecular detection therefore can be used in the diagnosis and differential diagnoses of craniopharyngiomas.

Objective:To analyze the clinical features and mutation of myeloid differentiation factor 88 (MYD88) L265P in patients with diffuse large B-cell lymphoma (DLBCL) of central nervous system (CNS).Methods:The clinicopathological materials of 45 cases of DLBCL of CNS were retrospectively collected in Xuanwu Hospital, Capital Medical University from September 2014 to February 2017. The clinicopathological data were retrospectively analyzed, combined with immunohistochemistry, EB virus in situ hybridization, imaging and medical history. The mutation of MYD88 L265P gene was detected by pyrosequencing and its clinical significance was analyzed. Results:The age of the patients ranged from 42 to 82 years [(57.6±8.8) years], including 24 males and 21 females. Totally 93.3% (42/45) of the patients had supratentorial tumours, which were single or multiple. The cerebral hemisphere (31/45, 68.9%) was the most common involved site, and 21 cases (21/45, 46.7%) had multiple lesions. Histologically, DLBCL in the CNS showed diffuse infiltration of tumor tissue, some of which grew around blood vessels in a "sleeve" arrangement. CD 20 and CD 79a were diffusely and strongly positive. Thirty-nine cases (39/45, 86.7%) were non-germinal center B cell (non-GCB) subtype and 6 cases (6/45, 13.3%) were germinal center B cell (GCB) subtype. MYD88 L265P mutation was found in 64.4% (29/45) patients. There was statistically significant difference between non-GCB type (71.8%, 28/39) and GCB type DLBCL (1/6, P=0.017). Compared with the operation/biopsy group without chemotherapy, operation+chemotherapy, biopsy+chemotherapy, operation/biopsy+chemotherapy+stem cell transplantation can improve the survival and prognosis ( HR=0.05, 95% CI 0.01-0.33 , P=0.002; HR=0.04, 95% CI 0.01-0.36 , P=0.004; HR=0.01, 95% CI 0.00-0.17 , P=0.001; respectively). Conclusions:DLBCL of the CNS is aggressive tumor with poor prognosis, the clinical manifestations are complex and diverse, and the diagnosis is challenging. MYD88 L265P is a common and specific gene mutation in primary CNS lymphoma(PCNSL), which is of great significance in the diagnosis and treatment of lymphoma. The MYD88 L265P mutation was more frequently detected in non-GCB than GCB subtype. Chemotherapy can improve the survival rate of PCNSL patients. If chemotherapy achieves complete remission and autologous hematopoietic stem cell transplantation is performed, there may be a chance of long-term survival.

Purpose To investigate the clinical pathology of SMARCB1/INI1-deficient poorly differentiated chordoma.Methods Ten patients with poorly differentiated chordoma were collected.The expression of CK,vimentin,INI1,and Brachyu-ry was detected using EnVision immunohistochemistry.Clinical characteristics,histopathological features,as well as related prognosis were analyzed and the literature was reviewed.Results Among the 10 cases,including 5 males and 5 females,the mean age of onset was 4 years.10 cases were located in the cliv-us and had bone invasion,3 involved the cervical spine(18.2％).In morphology,tumor cells showed sheet or nest mass growth,with epithelioid tumor cells.The nucleus was round or oval,with obvious atypia and visible nucleoli.Mitotic figures were active.Lymphocytic infiltration was noted in the stroma.Tumor cells in 10 cases were positive for CK,Vimen-tin,EMA and Brachyury with loss of SMARCB1/INI1 expres-sion.Ten patients were followed-up postoperatively.5 patients had tumor recurrence(median progression-free survival was 4 months)and 7 died(median overall survival was 5 months).Conclusion SMARCB1/INI1-deficient poorly-differentiated chordoma is a relatively rare bone tumor with poor prognosis and challenging diagnosis.Understanding the clinical pathological characteristics of this tumor has great significance for diagnosis and treatment.