Age is associated with prognosis in serous ovarian carcinoma

Abstract

Purpose: The survival duration of elderly patients with epithelial ovarian carcinoma is shorter than that of their younger counterparts. This variation in survival duration is likely attributed to differences in the distribution of histological type or grade, International Federation of Gynecology and Obstetrics (FIGO) staging, and undertreatment, but this observation remains controversial. This study aimed to investigate the biological factors other than selection bias associated with the decreased survival of elderly patients with ovarian carcinoma.

Methods: A total of 314 serous ovarian cancer (SOC) patients from Jiangsu Institute of Cancer Research (JICR, PRC) between 2002 and 2012 were retrospectively analyzed, and 774 cases from MD Anderson Cancer Center (MDACC, USA) between 1992 and 2012 were used for validation. The 8-hydroxy-2'-deoxyguanine (8-OHdG) concentration in leukocyte DNA was evaluated by using commercially available enzyme-linked immunosorbent assay kits, and tissue expression was assayed through immunohistochemistry. The associations between survival durations and covariates were assessed by using a Cox proportional hazards model and by conducting a log-rank test.

Results: Advanced age ≥ 65 years was correlated with high histological grade (p = 0.02), performance status (p = 0.03), primary treatment (p = 0.00), and suboptimal surgery outcome (p = 0.04) in SOC patients from JICR. Age, FIGO stage, histological grade, and optimal surgery were independently associated with the progression-free survival (PFS; p = 0.03, p = 0.03, p = 0.02, and p = 0.04, respectively) and overall survival (OS; p = 0.02, p = 0.04, p = 0.02, and p = 0.02, respectively) of the SOC patients from JICR. The 8-OHdG concentration in the leukocyte DNA was higher in the elderly patients than in the younger cases. The high 8-OHdG concentration in the leukocyte DNA indicated poorer median OS (30.0 months, confidence interval [CI]: 23.5-36.5 vs. 42.8 months, [CI] 38.3-47.2) and PFS (14.6 months, [CI] 11.9-17.2 vs. 18.9 months, [CI] 14.4-23.4) than those of their corresponding counterparts in the SOC patients who achieved a clinical complete response from primary treatment.

Conclusions: Compared with younger cases, elderly patients with SOC were commonly characterized by high tumor grade, poor performance status, and undertreatment. High 8-OHdG concentration in leukocyte DNA was associated with advanced age and poor prognosis in SOC patients.

Fig. 1

Histological grade and age were associated with mean concentrations of 8-OHdG in leukocyte DNA in serous ovarian carcinoma patients. Statistical significance was calculated using one-way ANOVA testing followed by post hoc analysis. *p < 0.05 vs. subjects with the characteristics in the blank bar

Fig. 2

Strong 8-OHdG positive nuclei can be observed in high grade serous ovarian carcinoma. Stromal reaction is negative and cytoplasm is immunopositive in places (a). Moderate 8-OHdG positive nuclei can be observed in high grade serous ovarian carcinoma, nuclear immunostaining is also found (b). Weak 8-OHdG positive nuclei can also be observed in high grade serous ovarian carcinoma (c). Negative control staining for 8-OHdG is also demonstrated in high grade serous ovarian carcinoma (d)

Fig. 3

Elderly patients had shorter overall survival and progression-free survival than younger cases with serous ovarian carcinoma from JICR (a, b)

Fig. 4

Increasing 8-OHdG concentration in leukocyte DNA is associated with poor prognosis of serous ovarian carcinoma patients received compete clinical response. a Low 8-OHdG concentration was associated with longer overall survival duration (42.8 vs. 30.0 months, p = 0.01); b Low 8-OhdG concentration was associated with longer progression-free survival duration (18.9 vs.14.6 months, p = 0.04)