Oncology Intelligence

Thymous Cancer
Sunday, September 18, 2016 10:27 AM|Head and Neck Oncology|Labels: thymic
Papillary thyroid carcinoma is the most common type of well-differentiatedthyroid carcinoma. Metastases usually occur in regional lymph nodes. Here,we report a patient with unusual metastases from papillary thyroidcarcinoma.A 55-year-old woman had a history of right papillary thyroid carcinoma and underwent local excision of the right thyroid lobe in another hospital previously. The patient was found to have metastatic papillary thyroid carcinoma to the left parietooccipital lobe, bilateral lung, the left caput humeri, the left triceps brachii muscle, the right collum ossis femoris and left thumb. She eventually suffered multiple organ failure and died. Therefore, if not timely and thorough treatment, papillary thyroid carcinoma may alsometastatic to brain, lung, askeletal muscle, bone and other various sites through direct hematogenic routes.
Friday, September 16, 2016 4:27 PM|Fu Gao, Song Chen, Mingjuan Sun, Ronald E.J. Mitchel, Bailong Li, Zhiyong Chu, Jianming Cai, Cong Liu|International Journal of Biological Sciences|Labels: thymic

It has been reported dysregulation of certain microRNAs (miRNAs / miRs) is involved in tumorigenesis. However, the miRNAs associated with radiocarcinogenesis remain undefined. In this study, we validated the upregulation of miR-467a in radiation-induced mouse thymic lymphoma tissues. Then, we investigated whether miR-467a functions as an oncogenic miRNA in thymic lymphoma cells. For this purpose, we assessed the biological effect of miR-467a on thymic lymphoma cells. Using miRNA microarray, we found four miRNAs (miR-467a, miR-762, miR-455 and miR-714) were among the most upregulated (>4-fold) miRNAs in tumor tissues. Bioinformatics prediction suggests miR-467a may potentially regulate apoptosis pathway via targeting Fas and Bax. Consistently, in miR-467a-transfected cells, both proliferation and colony formation ability were significantly increased with decrease of apoptosis rate, while, in miR-467a-knockdown cells, proliferation was suppressed with increase of apoptosis rate, indicating that miR-467a may be involved in the regulation of apoptosis. Furthermore, miR-467a-knockdown resulted in smaller tumors and better prognosis in an in vivo tumor-transplanted model. To explain the mechanism of apoptosis suppression by miR-467a, we explore the expression of candidate target genes (Fas and Bax) in miR-467a-transfected relative to negative control transfected cells using flow cytometry and immunoblotting. Fas and Bax were commonly downregulated in miR-467a-transfected EL4 and NIH3T3 cells, and all of the genes harbored miR-467a target sequences in the 3'UTR of their mRNA. Fas and Bax were actually downregulated in radiation-induced thymic lymphoma tissues, and therefore both were identified as possible targets of miR-467a in thymic lymphoma. To ascertain whether downregulation of Fas and / or Bax is involved in apoptosis suppression by miR-467a, we transfected vectors expressing Fas and Bax into miR-467a-upregulated EL4 cells. Then we found that both Fas- and Bax-overexpression decreased cell viability with increase of apoptosis rate, indicating that downregulation of Fas and Bax may be at least partly responsible for apoptosis suppression by miR-467a. These data suggest that miR-467a may have oncogenic functions in radiation-induced thymic lymphoma cells and that its increased expression may confer a growth advantage on tumor cells via aberrant expression of Fas and Bax.

Thursday, September 15, 2016 3:30 PM|ETJ : Last 10 articles|Labels: BRAF, thymic
Background: The BRAFV600E mutation is common in papillary thyroid cancer (PTC). Lymph node metastasis (LNM) may be associated with poor prognosis. However, the LNM mechanism remains unclear. Objectives: Our aim was to evaluate the prevalence of the BRAFV600E mutation in primary tumors and accompanying LNM at the time of diagnosis. Methods: This retrospective study included 51 PTC patients (40 women, 11 men; mean age 40.0 ± 16.5 years; range 6-81) who underwent total thyroidectomy accompanied by a lateral neck dissection due to preoperatively detected LNM. Real-time PCR was used for the detection of the BRAFV600E mutation in specimens from primary thyroid tumors and metastatic lymph node tumors. Results: The prevalence of the BRAFV600E mutation was 64.7% (n = 33) in primary tumors and 47.1% (n = 24) in metastatic lymph nodes. Of 33 patients with BRAFV600E-positive primary tumors, 18 (54.5%) had BRAFV600E-positive metastatic lymph nodes. Of 18 patients with BRAFV600E-negative primary tumors, 6 (33.3%) had BRAFV600E-positive metastatic lymph nodes. The presence of the BRAFV600E mutation in the primary tumor did not affect the tumor size, but the diameter of metastatic lymph nodes significantly increased (by nearly 3 mm) with the presence of BRAFV600E in LNM (p = 0.01). Conclusions: In our study, the BRAFV600E mutation did not show a one-to-one correspondence. This indicates that the presence of BRAFV600E in the primary tumor is not clonal and addresses the role of intratumor heterogeneity in PTC tumorigenesis. This supports the theses that mutations occur in the later stages of tumorigenesis, might be subclonal, and develop de novo, or that some other factors may be involved in the development of metastasis.
Eur Thyroid J
Thursday, September 15, 2016 7:42 AM|K.|JournalTOCs API - Clinical Cancer Research (27 articles)|Labels: PD-1/PD-L1, thymic

PD-L1 and PD-1 Expression in Thymic Carcinoma
Yokoyama, S Miyoshi, H, Nakashima, K, Shimono, J, Hashiguchi, T, Mitsuoka, M, Takamori, S, Akagi, Y, Ohshima, K.
Clinical Cancer Research, Vol. 22, No. 18 (2016) pp. 4727 - 4734
Purpose: The immune checkpoint of the programmed death 1/programmed death ligand 1 (PD-1/PD-L1) pathway is believed to play an important role in evasion of host antitumor immune surveillance in various malignancies; however, little is known about its role in thymic carcinoma. This study investigated PD-1/PD-L1 expression and its association with clinicopathologic features, the expression of immune-related proteins in tumor-infiltrating lymphocytes (TIL), and patient prognosis. Experimental Design: PD-L1 and PD-1 expression was evaluated by IHC in 25 thymic carcinoma tissue specimens. Copy number alterations of the PD-L1 gene in 11 cases were assessed in formalin-fixed, paraffin-embedded material using qRT-PCR. Results: Compared with normal subjects, 3 thymic carcinoma patients showed an increase in PD-L1 copy number, whereas 8 did not. PD-L1 was significantly overexpressed in cases with copy number gain as compared with normal cases. High PD-L1 expression was associated with higher disease-free and overall survival rates as compared to cases with low expression. Prognostic analysis revealed low PD-L1 expression and high number of PD-1+ TILs as significant predictors of poor survival, together with Masaoka–Koga stage IVa/IVb disease and incomplete resection. In the quantitative analysis of TILs, PD-L1 expression correlated proportionally with the number of infiltrating CTLs. Conclusions: Here, for the first time, we report that PD-L1 and PD-1 expression might be useful prognostic predictors in thymic carcinoma. Further studies are expected to substantiate the prognostic value of PD-L1 and PD-1 expression, and the potential efficacy of targeting the PD-1/PD-L1 pathway in thymic carcinoma via immunotherapy. Clin Cancer Res; 22(18); 4727–34. ©2016 AACR.

CONCLUSIONSThese data suggest that cabozantinib provides the greatest clinical benefit to patients with MTC who have RET M918T or RAS mutations. However, a prospective trial is needed to confirm the relation between genetic variation and the response to cabozantinib. Cancer 2016. © 2016 American Cancer Society. (Source: Cancer)
Thursday, July 14, 2016 10:05 PM|Yu, X.-M., Jaskula-Sztul, R., Georgen, M. R., Aburjania, Z., Somnay, Y. R., Leverson, G., Sippel, R. S., Lloyd, R. V., Johnson, B. P., Chen, H.|Clinical Cancer Research recent issues|Labels: Notch, thymic

Purpose: Notch1, a transmembrane receptor, has been recently shown to aid in the determination of thyroid cell fate associated with tumorigenesis. This study aimed to investigate the clinical relevance of Notch1 and its role in the regulation of differentiated thyroid cancer (DTC) behavior.

Experimental Design: We examined Notch1 expression level and its relationship with clinicopathologic features and outcomes of DTC. Notch1 intracellular domain (NICD) was further characterized both in vitro and in vivo by gain-of-function assays using an inducible system.

Results: Notch1 expression levels were downregulated in primary DTC tissue samples compared with contralateral nontumor and benign thyroid tissues. Decreased Notch1 expression in DTC was associated with advanced patient age (P = 0.032) and the presence of extrathyroidal invasion (P = 0.005). Patients with lower Notch1 expression had a significantly higher recurrence rate (P = 0.038). Restoration of NICD in a stably doxycycline-inducible metastatic DTC cell line reduced cell growth and migration profoundly. Using an orthotopic thyroid cancer model, NICD induction significantly reduced the growth of the primary thyroid tumor and inhibited the development of lung metastasis. Serpin peptidase inhibitor, clade E, member 1 (SERPINE1) was discovered by microarray as the most significant gene downregulated by NICD. Further validation showed that the induction of NICD reduced SERPINE1 expression in a dose-dependent manner, whereas restoration of a relative higher level of SERPINE1 was observed with NICD back to minimal level. In addition, SERPINE1 knock-down inhibited DTC cell migration.

Conclusions: Notch1 regulates the aggressive phenotypes of DTC, which could be mediated by SERPINE1 inhibition. Notch1/SERPINE1 axis warrants further investigation as a novel therapeutic target for advanced DTC. Clin Cancer Res; 22(14); 3582–92. ©2016 AACR.

Tuesday, May 31, 2016 3:00 PM|Pathology International|Pathology International via|Comments|Labels: thymic
We report a very rare case of combined thymic carcinomas: undifferentiated thymic carcinoma coexisting with type AB thymoma. The precise mechanism underlying the coexistence of these tumors remains unknown. Therefore, we used clonality analysis to ascertain whether the two tumors were clonally related. A 63‐year‐old woman with thyroid cancer visited our hospital. Chest computed tomography also revealed an anterior mediastinal tumor. The patient was treated with total thyroidectomy and surgery for mediastinal tumors together with left upper lobe partial resection. The mediastinal tumor was pathologically diagnosed as undifferentiated thymic carcinoma coexisting with type AB thymoma. Multiple pulmonary metastases were detected in the patient and stage IV disease was diagnosed. The tumor ...