GTF2I Mutation in Thymomas: Independence From Racial-Ethnic Backgrounds. An Indian/German Comparative Study.

Thymomas are the most frequent adult mediastinal cancers. Their etiology is unknown and their pathogenesis poorly understood. Racial, ethnic and environmental factors influence tumorigenesis in many cancers, but their role in thymomas remains unclear to date. In this study that included pretreatment thymoma cases from India and Germany (n = 37 and n = 77, respectively) we compared i) the prevalence of the thymoma-specific chromosome 7 c.74146970T > A mutation of the GTF2I gene in type A and AB thymomas; ii) epidemiological features; and iii) the frequency of myasthenia gravis (MG). Due to a known predominance of GTF2I mutation in A and AB histotypes, we included only a marginal number of type B thymomas as a control group in both cohorts. While the distribution of histological types between the cohorts was similar (p = 0.1622), Indian patients were strikingly younger (p < 0.0001; median age 50 vs. 65 years) and showed significantly lower tumour stage (Masaoka-Koga stage I) at primary diagnosis (p = 0.0005) than the German patients. In patients with known MG status (n = 17 in Indian and n = 25 in German cohort), a clear trend towards more frequent MG was observed in the Indian group (p = 0.0504; 48 vs. 82%). The prevalence of the GTF2I mutation (analysed in n = 34 Indian and n = 77 German patients) was identical in the two cohorts. We conclude that racial-ethnic and environmental factors do not significantly influence the most common molecular feature of thymomas but may have an impact on the timing of clinical presentation.

Racial Disparity in Surgical Therapy for Thymic Malignancies.

BACKGROUND: The primary curative treatment for thymic malignancies is surgery. For lung and esophageal cancer, substantive disparities in outcomes by race exist. Many of these disparities are attributed to the decreased use of surgery in non-White patients. Although thymic malignancies are treated by the same specialists as lung and esophageal cancer, it is unknown if there are racial disparities in the treatment of thymic malignancies. RESEARCH QUESTION: Do racial disparities exist in the surgical treatment of thymic malignancies? STUDY DESIGN AND METHODS: A retrospective cohort analysis was performed using the National Cancer Data Base of patients diagnosed with thymoma and thymic carcinoma between 2004 and 2016. Univariate comparisons of demographics were compared using χ 2 and rank-sum tests. Multivariable analysis was performed to determine if race was an independent variable associated with receiving surgical resection. Preoperative and postoperative care was compared between races. RESULTS: Seven thousand four hundred eighty-nine patients met inclusion criteria. Four thousand nine hundred sixty-two (66%) were White, 1,311 (18%) were Black, 487 (7%) were Hispanic, 580 (8%) were Asian or Pacific Islander, and 143 (2%) were other races. Black patients with thymic malignancies were more likely to have a median income < $38,000 and not received surgery. Black and Hispanic patients had the lowest median age (54.3 and 53.6 years, respectively) and were most likely to be uninsured (8.2% and 12.5%, respectively). White patients received surgical therapy 1 week sooner and had a postoperative length of stay 1.5 days shorter than Black patients. Multivariable analysis controlling for age, sex, tumor size, insurance status, comorbidity score, histology, and facility type showed that race remained independently associated with the receipt of surgical resection. White patients had the greatest likelihood of receiving surgery with Black patients being least likely to receive surgery (OR, 0.60). INTERPRETATION: A racial disparity exists in surgical therapy for thymic malignancies.

Mutation analysis of the EGFR gene and its downstream signaling pathway in thymic carcinoma patients from a Chinese Han population.

INTRODUCTION: For thymic carcinoma (TC), which is a rare epithelial neoplasm of the thymus gland, median survival with current treatments is only 2 years. OBJECTIVES: Mutations in the epidermal growth factor receptor (EGFR) gene or its downstream effectors may cause constitutive activation that leads to cell proliferation and metastases. Thus, molecular profiling is essential for selecting TC patients who may respond to anti-EGFR therapies. METHODS: Genomic DNA was extracted from 61 histological samples of TCs. Real-time polymerase chain reaction (PCR) and direct sequencing were used to assess the mutations in the EGFR downstream pathway. RESULTS: Gene mutations were identified in seven patients (11.5%). In particular, the identified mutations included four mutations in the KRAS gene, one mutation in the BRAF gene, one mutation in the PIK3CA gene, and only one mutation in the EGFR gene itself. Gene mutations in the EGFR downstream pathway were associated with shorter survival time and were observed to be an independent prognostic factor for TC patients. CONCLUSION: Mutations in the EGFR downstream pathway are not rare in TCs. These data offer interesting possibilities for the future management of TCs, particularly in the era of new targeted therapies.

The association of HLA-DQA1*0401 and DQB1*0604 with thymomatous myasthenia gravis in northern Chinese patients.

Genetic analyses indicate that HLA complex genes can be involved in susceptibility to autoimmune myasthenia gravis (MG). Various HLA alleles serve as genetic elements that either predispose to or protect against MG. This study investigates the probable relationship between HLA-DQ allele polymorphisms and MG cases in northern China. The HLA-DQA1 and DQB1 alleles were determined by polymerase chain reaction/sequence-specific primers (PCR-SSP) in 84 MG patients, and the results were compared to 293 healthy controls. Our findings indicate that DQ A1*0401(P=0.008, OR: 2.5, 95%CI: 1.24-3.07) and B1*0301(P=0.000, OR: 2.29, 95%CI: 1.48-3.54) were the most frequent allele; the frequencies of DQA1*0103(P=0.000, OR:0.24, 95%CI 0.13-0.49) and DQB1*0601(P=0.001, OR:0.40, 95%CI 0.22-0.50) were significantly decreased in MG patients compared with healthy controls. Patients with thymomatous MG were positively associated with DQA1 *0401(P=0.011, OR:4.57, 95% CI 1.40-14.90) and DQB1 *0604 (P=0.001, OR:4.01, 95% CI 1.65-9.73) as compared to MG patients without thymoma. Different genetic mechanisms may exist between MG patients with thymoma and those without thymoma. The HLA-DQ associations in MG subgroups suggest that disease heterogeneity may be influenced by different genes or alleles.