BRAF V600E mutation co-existing with oncogenic mutations is associated with aggressive clinicopathologic features and poor prognosis in papillary thyroid carcinoma.

BACKGROUND: The aim of this study was to evaluate the correlation among mutations in cancer-related genes, clinicopathologic features, and clinical outcome in classical papillary thyroid carcinoma (PTC). PATIENTS AND METHODS: A total of 130 patients with classical PTC who underwent curative surgery between April 2012 and June 2023 at Hokuto Hospital were included. Mutations in targeted regions of 160 cancer-related genes were detected by next-generation sequencing (NGS)-based cancer panel testing. RESULTS: The BRAF V600E mutation was detected in 108 (83.1%) of 130 PTC patients. Among the 108 patients with the BRAF V600E mutation, other co-existing oncogenic mutations were found in 12 (9.2%) patients. When we divided into 3 groups of no mutations, BRAF V600E mutation alone, and BRAF V600E and other oncogenic mutations, significant differences were observed in terms of tracheal invasion (P = 0.0024), and bilateral neck lymph node metastasis (P = 0.0047). Kaplan-Meier analysis of overall survival (OS) revealed patients with BRAF V600E and other oncogenic mutations had significantly poorer survival than those with BRAF V600E mutation alone (P = 0.0026). Multivariate cox proportional hazard analysis revealed BRAF V600E and other oncogenic mutations was an independent prognostic factor for OS (HR: 10.559; 95%CI: 1.007-110.656, P = 0.0493). CONCLUSIONS: The BRAF V600E mutation co-existing with other oncogenic mutations but not the BRAF V600E mutation alone was associated with aggressive clinicopathologic features, resulting in poor prognosis in patients with classical PTC. Detection of oncogenic mutations using NGS-based cancer panel testing could enhance understanding of the clinical features of classical PTC.

Prognostic impact of tumor-associated neutrophils in breast cancer.

OBJECTIVES: Neutrophils are the most common type of leukocyte in mammals and play an essential role in the innate immune system and anti-cancer responses. However, recent studies identified the presence of tumor-associated neutrophils (TANs) as a poor prognostic factor. The present study investigated whether relationships exist between TANs and the clinicopathological factors and genetic status of breast cancer. METHODS: A total of 196 breast cancer patients with sufficient biopsy, breast-conserving surgery, or mastectomy specimens between 2014 and 2021 in Hokuto Hospital were included. RESULTS: TANs were individually counted in the tumor stroma (TS) and tumor nest (TN). A higher density of TANs in both TS and TN correlated with tumor size (TS P = 0.010; TN P = 0.001), a high histological grade (TS P < 0.001; TN P < 0.001), the histological type (TS P = 0.009; TN P = 0.034), a high ratio of lymph node metastasis (TS P < 0.001; TN P < 0.001), an advanced stage of cancer (TS P < 0.001; TN P = 0.002), intrinsic subtypes (TS P < 0.001; TN P < 0.001), ERBB2 (TS P < 0.001; TN P < 0.001), MAP3K1 (TS P = 0.002; TN P = 0.023), and TP53 (TS P < 0.001; TN P < 0.001). A higher density of TANs in TS and TN also correlated with shorter disease-free survival and overall survival (P < 0.001). CONCLUSION: The present results suggest that a higher density of TANs correlates with unfavorable prognostic factors in breast cancer. Further research on clinicopathological and genetic factors associated with TANs in breast cancer is needed.

A retrospective study of parotid gland tumors at a single institution.

The aim of the present study was to analyze the clinical characteristics, surgical treatments and clinical outcome of patients with parotid gland tumors and to compare the results with those cited in the literature. A retrospective study was conducted in 140 patients (male, n=77; female, n=63) with parotid gland tumors who underwent parotidectomy at Hokuto Hospital Department of Otolaryngology-Head and Neck Surgery (Obihiro, Japan) between April 2007 and December 2021. Of the 140 patients enrolled, 118 (84.3%) patients had benign tumors, including 63 (45%) patients with pleomorphic adenomas and 43 (30.7%) patients with Warthin tumors, and 22 patients (15.7%) had parotid carcinoma. Comparison of the three groups of patients with parotid gland tumors indicated that pack years as an indicator of smoking status were significantly higher in patients with Warthin tumors than in those with parotid carcinomas (P=0.011) or pleomorphic adenoma (P<0.001). Fine-needle aspiration cytology (FNAC) was non-diagnostic for only 6 (4.3%) of 140 patients. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of FNAC by both conventional smear and liquid-based cytology (LBC) for parotid carcinomas were 70, 99, 93.3, 94.4 and 82.9%, respectively. Among the 22 patients with parotid carcinoma, extended total/total and superficial parotidectomy were performed in 10 (45%) and 11 (50%) cases, respectively. Total and selective neck dissection of the area from level II to I, II and III were performed in 6 (24%) and 7 (32%) patients, respectively. Postoperative radiotherapy (50 Gy) was performed in 15 (68%) patients. The overall survival (OS) and disease-free survival (DFS) rates at 5 years were 51.5 and 76.4%, respectively. Univariate analysis revealed that age >65 years was significantly associated with poorer 5-year OS (P<0.001) and DFS (P<0.001). Multivariate analysis revealed that an age of more than 65 years combined with high-grade histologic malignancy was associated with worse DFS (P=0.02; hazard ratio, 3.628; 95% confidence interval, 1.283-9.514). In conclusion, the clinical characteristics and treatment outcomes of parotid gland tumors were consistent with the results of previous reports. Smoking may be closely related to the pathogenesis of Warthin tumors. LBC potentially provides improved accuracy in FNAC.