Relationship between mitochondrial succinate dehydrogenase gene mutation and clinicopathological features of carotid body tumor and its predictive value for prognosis

Objective To analyze the correlation between mitochondrial succinate dehydrogenase (SDH) subunit (A, B, C, D) gene mutations and clinicopathological features of carotid body tumor (CBT) and to explore its prognostic value. Methods Ninety-five patients with sporadic CBT (CBT group) (male 43/female 52), aged 39-70 years old, were all unilateral tumors (55 left/40 right), with tumor diameter of 1.5-10.0 cm. Glenner’s classification was as follows: chemoreceptor tumor in 47 cases, pheochromocytoma in 44 cases, mixed type in 4 cases. The 95 healthy subjects (male 41/female 54), aged 10-69, were selected as the healthy group. PCR was used to amplify the exons of each sub unit gene of SDH and determine the DNA sequence. The gene mutation rate of each sub unit of SDH in CBT group and healthy group was compared. The relationship between the subunits with different mutation rate and the clinicopathological characteristics of the patients and the influence on the prognosis and survival were analyzed, and its predictive value to prognosis was analyzed by logistic regression analysis, and the survival rate of Kaplan Meier was analyzed. Results The mutation rate of SDHB and sDHD in CBT group was 26.32% and 8.84%, respectively. There were no significant differences in the mutation rate of SDHA, SDHC and SDHD between the CBT group and the healthy group (χ2=2.021, 2.212, P>0.05). The mutation rate of SDHB in the CBT group was significantly higher than that in the healthy group (χ2=18.472, P 0.05). The proportion of capsule incompleteness, infiltration of adjacent soft tissue and lymph node metastasis in SDHB mutation group was significantly higher than that in SDHB mutation group (χ2/Z=4.859, 5.566, 9.365, P<0.05). Logistic regression analysis showed that age over 60 years old, incomplete capsule, infiltration of adjacent soft tissue, lymph node metastasis and SDHB mutation were all risk factors for poor prognosis of CBT patients [odds ratio (OR)=2.264, 3.596, 3.117, 3.320, 2.440, P<0.05]. The median follow-up time of 95 patients was 42 months. The 3-year disease-free survival rate of the patients in the non-mutation group and the mutation group was 95.71% and 64.00%, respectively, and the analysis of survival curve showed that the 3-year disease-free survival rate of patients in the non-mutation group of SDHB was significantly higher than that in the mutation group of SDHB (χ2=7.309, P<0.05). Conclusion CBT patients are easy to carry SDHB and SDHD mutation genes. The SDHB mutation gene is closely related to CBT differentiation degree, presence or absence of distant metastasis and prognosis. Key words: Carotid body tumor; Mitochondrial succinate dehydrogenase; Gene mutation; Pathological features; Prognosis