Downregulation of KLF5 by EBER1 via the ERK signaling pathway in EBV-positive nasopharyngeal carcinoma cells: implications for latent EBV infection.

Nasopharyngeal carcinoma (NPC) carcinogenesis and malignant transformation are intimately associated with Epstein-Barr virus (EBV) infection. A zinc-fingered transcription factor known as Krüppel-like factor 5 (KLF5) has been shown to be aberrantly expressed in a number of cancer types. However, little is known about the regulatory pathways and roles of KLF5 in EBV-positive NPC. Our study found that KLF5 expression was significantly lower in EBV-positive NPC than in EBV-negative NPC. Further investigation revealed that EBER1, which is encoded by EBV, down-regulates KLF5 via the extracellular signal-regulated kinase (ERK) signalling pathway. This down-regulation of KLF5 by EBER1 contributes to maintaining latent EBV infection in NPC. Furthermore, we uncovered the biological roles of KLF5 in NPC cells. Specifically, KLF5 may influence the cell cycle, prevent apoptosis, and encourage cell migration and proliferation - all of which have a generally pro-cancer impact. In conclusion, these findings offer novel strategies for EBV-positive NPC patients' antitumour treatment.

Quantitative Radiological Features and Deep Learning for the Non-Invasive Evaluation of Programmed Death Ligand 1 Expression Levels in Gastric Cancer Patients: A Digital Biopsy Study.

RATIONALE AND OBJECTIVES: Programmed Death-Ligand 1 (PD-L1) is an important biomarker for patient selection of immunotherapy in gastric cancer (GC). This study aimed to construct and validate a non-invasive virtual biopsy system based on radiological features and clinical factors to predict the PD-L1 expression level in GC. MATERIALS AND METHODS: 217 patients who received gastrectomy for GC were consecutively enrolled in this study, with 157 patients from center 1 as the training cohort and 60 patients from center 2 as the external validation cohort. 1205 quantitative radiomics features were extracted from preprocessed pre-operative contrast-enhanced CT images of enrolled patients. A radiological signature was computed using a regression random forest model and was integrated with clinical factors in a multilayer perceptron. The performance of the digital biopsy system was evaluated by the receiver operating characteristic (ROC) curve and calibration curve in both the training and validation cohort. RESULTS: 15 features were selected for the construction of radiological signature, which was significantly associated with expression levels of PD-L1 in both the training cohort (p<0.0001) and the external validation cohort (p<0.01). The hybrid deep learning model integrating the radiological signature and clinical factor could accurately distinguish GCs with high PD-L1 expression levels in both the training cohort (AUC = 0.806, 95%CI: 0.736-0.875) and the validation cohort (AUC = 0.784, 95%CI: 0.668-0.901). CONCLUSIONS: Our results indicate that the combination of deep learning and quantitative radiological features are potential approaches for the non-invasive evaluation of PD-L1 expression levels in GC. The digital biopsy system could provide valuable suggestive information for clinical decision-making of immunotherapy in GC.

Qualitative and Quantitative Anatomy of the Deep Radioulnar Ligaments' Insertion on Ulna: Cadaveric, Histologic, and MRI Study.

PURPOSE: To qualitatively and quantitatively analyze the anatomic features of the insertion of deep radioulnar ligaments (RULs) and provide an anatomic basis for further studies. METHODS: The anatomic features of deep RUL insertion were observed macroscopically in 26 cadaveric wrists, after which the size of the deep RUL footprint and distance from the center of the footprint to the ulnar-sided margin of articular cartilage of the ulnar head were each measured. Five specimens were analyzed histologically to examine the attachment of the RUL on the ulna. In addition, we evaluated 21 asymptomatic wrists from healthy volunteers using 3.0 T magnetic resonance imaging. RESULTS: The insertion of the deep RUL was located mainly on the radial aspect of the ulnar fovea from the foveal center to the articular cartilage. The footprint of the deep RUL appeared in 3 different shapes. The maximal width, length, and area of the footprint of the deep RUL were 3.7 (95% confidence interval [CI], 3.3-4.0) mm, 8.4 (95% CI, 7.9-8.9) mm, and 26.3 (95% CI, 23.4-29.1) mm2, respectively. Histologic analyses showed the attachment of the deep RUL on the radial wall of the fovea exhibited a direct insertion with typical 4-layer structures. The deep RUL fibers formed an acute angle with the distal component of the triangular fibrocartilage complex. CONCLUSIONS: The deep RUL was inserted on the radial side of the ulnar fovea and not the foveal center; it had direct insertion on the radial wall continuous with articular cartilage, and the fibers in the direct insertion formed an acute angle with the distal component of the triangular fibrocartilage complex. CLINICAL RELEVANCE: Understanding the quantitative anatomy of the deep RUL insertion may help guide surgeons to perform an anatomic foveal repair of the triangular fibrocartilage complex in its native footprint.

Bronchiolar adenoma-like tumour with monolayered component: Represent malignant transformation of bronchiolar adenoma? A series of five cases.

Pulmonary bronchiolar adenoma (BA) is a rare lung tumour, it is unclear whether BA can develop into a malignancy. We presented five cases of BA-like tumour with monolayered components. This type of tumour may represent the malignant transformation of BA. Histologically, these tumours showed acinar and lepidic growth patterns. The acinar components were well-differentiated. The glandular tumour cells in these tumours contained cuboidal to columnar cells resembling type II pneumocytes or club (Clara) cells. A small number of mucinous cells were found in two cases. A few scattered ciliated cells were detected in three cases. The ciliated cells only existed in the bilayered components. The basal cells were highlighted by CK5/6 and p40 in a partial region of the tumour rather than in the entire tumour. The glandular tumour cells, including those in the bilayered component, were diffusely positive for TTF-1 and napsin-A. EGFR Exon19 deletions were found in four cases, and BRAF V600E mutation was found in one case. These BA-like tumours have biphasic morphological and molecular characteristics of BA and lung adenocarcinoma, suggesting distal-type BA may develop into a malignancy. More cases should be studied and especially cases with metastasis should be searched to further prove the malignant transformation.

MED12 exon 2 mutation is uncommon in intravenous leiomyomatosis: clinicopathologic features and molecular study.

Intravenous leiomyomatosis (IVL) is a rare neoplasm that is characterized by smooth muscle cell proliferation within venous vessels. The aim of this study is to investigate the clinicopathological features, immunophenotypes, and MED12 gene mutations in IVL. Nine cases of IVL from the Affiliated Hospital of Qingdao University were collected, and the clinicopathological features were reviewed. The immunohistochemical expressions of p16, phosphatase and tensin homolog deleted on chromosome 10 (PTEN), alpha thalassemia/mental retardation syndrome X-linked (ATRX), retinoblastoma 1 (RB1), fumarate hydratase (FH), and p53, were evaluated. The mutation status of MED12 gene exon 2 was detected by Sanger sequencing. All the 9 patients were women ranging from 32 to 58 years, and uterine leiomyomas were identified in 5 patients. Immunohistochemical staining showed that all IVL and leiomyoma samples were positive for estrogen receptor and progesterone receptor, but negative for CD34. IVL displayed similar immunostaining patterns with their uterine counterparts with focal p16 immunostaining. FH, PTEN, ATRX, and RB1 were variably positive, and p53 and Ki-67 positive rates were less than 5% in all cases. Two novel genetic variations at MED12 exon 2, a synonymous mutation c.141C>T (p.Asn47=), and an in-frame deletion mutation c.133_147del15 (p.Phe45_Pro49del) were identified in two IVL cases. One missense mutation c.131G>A (p.Gly44Asp) was identified in one uterine leiomyoma. The remaining 11 tumor samples (7 IVL cases and 4 uterine leiomyomas) showed no mutations at MED12 exon 2. Our results showed two novel MED12 mutations in IVL. The MED12 mutations are different between IVL and uterine leiomyoma. These findings indicate that IVL is a unique entity and different from uterine leiomyoma.

Cerebral metastases of parathyroid carcinoma: a case report and literature review.

Parathyroid carcinoma (PC) is an uncommon endocrine tumor. At first presentation, the diagnosis of PC by morphologic analysis is challenging. Indeed, approximatively 50% of metastatic PCs were categorized as benign at the time of first resections. However, single brain metastasis rarely occurs in PC patients and could represent a further obstacle for PC diagnosis in the absence of other symptoms. The present report describes the clinicopathological features of a case of PC intracranial metastases in a 60-year-old woman, who presented space-brain occupying symptoms as a first manifestation. To the best of our knowledge, only ten cases with brain metastasis were reported in the literature.

Primary cardiac lymphoma in both atria: A case report.

Primary cardiac lymphoma (PCL) is a very rare kind of primary heart tumor, belonging to non-Hodgkin's lymphoma whose major pathological type is diffuse large B-cell lymphoma. The common symptoms include heart failure, pericardial effusion, and malignant arrhythmias. Early diagnosis and treatment of PCL are of great importance due to its merely 7-month median survival period. Here, we report a 48-year-old male patient in whom both atria were involved and had to undergo palliative surgery because of severe clinical symptoms.

[Analysis of the protein expression and gene amplification of HER2 in gastric cancer].

OBJECTIVE: To explore the clinical significance of protein expression and gene amplification of HER2 in gastric cancer. METHODS: Immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH) method were used to detect protein expression and gene amplification of HER2 in 80 specimens of gastric cancer patients. RESULTS: Protein expression of HER2 was negative in 51 cases, (+) in 12 cases, (++) in 12 cases, (+++) in 5 cases, and the positive expression rate was 21.3% (17/80). Seven (8.8%) cases had gene amplification of HER2, including gene critical amplification in 3 (3.8%) cases. The result of IHC was positively correlated with CISH (P<0.05), and the coincidence rate was 85.0% (68/80). HER2 positive expression rate was higher in the gastroesophageal junction carcinoma, poorly differentiated and stage III-IIII gastric cancer (all P<0.05). CONCLUSION: The gastric cancer tissue has high positive rate of protein expression and gene amplification of HER2, which is closely correlated to the development of gastric cancer.

Pulmonary mixed squamous cell and glandular papilloma mimicking adenocarcinoma: a case study and literature review.

Mixed squamous cell and glandular papilloma of the lung is an extremely rare benign neoplasm. Here we present another case of mixed squamous cell and glandular papilloma in a 64-year-old female nonsmoker. Histologically, the tumor was composed of mainly papillary structures covered with squamous, glandular and transitional epithelium. Some glandular structures extending into adjacent bronchiolar and alveolar spaces with mucus were similar to adenocarcinoma. Immunohistochemical analysis showed the different kinds of epithelia had similar immunophenotype. The different components were positive for cytokeratin (CK)7, CK19, CAM5.2, CK5/6, CK34ßE12, and TTF-1, but negative for CK20. The transitional morphology and immunohistochemistry indicate the different components likely come from a same kind of progenitor in the bronchiolar wall.

Primary pleomorphic malignant fibrous histiocytoma of the heart.

Primary pleomorphic malignant fibrous histiocytoma of the heart is rare. The present study was performed to study the clinical and pathological features of the disease. We describe two rare cases of primary cardiac malignant fibrous histiocytoma and review the published individual data of the patients. Both patients complained of dyspnea, and underwent palliative tumor resection. However, they died several months after surgery. A thorough literature review with clinical presentations, diagnostic features, treatment, and outcomes was done. We have for the first time analyzed the factors related to the survival of malignant fibrous histiocytoma. It is usually difficult to make an appropriate preoperative diagnosis. Despite complete surgical resection and aggressive chemotherapy and radiotherapy, the prognosis is still poor.

[Primary cardiac neoplasms: a clinicopathologic analysis of 81 cases].

OBJECTIVE: To study the disease spectrum, clinical and pathologic features of primary cardiac neoplasms at a single medical institution during a period of eight years. METHODS: The clinical and pathologic features of 81 cases of primary cardiac neoplasms encountered at the Affiliated Hospital of Medical College, Qingdao University from January, 2004 to December, 2011, either for cardiovascular surgery or as pathology consultation cases, were retrospectively reviewed. Immunohistochemical study was carried out in selected examples. RESULTS: Amongst the 81 cases studied, 73 cases (90.1%) were benign and 8 cases (9.9%) were malignant. Cardiac myxomas accounted for 97.3% (71/73) of all the benign cases. Six of the 8 malignant cases represented soft tissue sarcomas. The commonest presenting symptom was dyspnea. The histologic subtypes included myxoma (number = 71), angiosarcoma (number = 2), malignant fibrous histiocytoma (number = 2), hemangioma (number = 1), liposarcoma (number = 1), lymphoma (number = 1), myxofibrosarcoma (number = 1) and papillary fibroelastoma (number = 1). CONCLUSIONS: While the majority of primary cardiac neoplasms are myxomas, other tumor types do exist. Accurate histologic diagnosis and timely surgery are crucial in patient management.