BRCA1, Ki67, and β-Catenin Immunoexpression Is Not Related to Differentiation, Platinum Response, or Prognosis in Women With Low- and High-Grade Serous Ovarian Carcinoma

Sallum, Luis Felipe; Andrade, Liliana Aparecida Lucci De Angelo; Costa, Larissa Bastos Eloy da; Ramalho, Susana; Ferracini, Amanda Canato; Natal, Rodrigo de Andrade; Brito, Angelo Borsarelli Carvalho; Sarian, Luís Otávio; Derchain, Sophie

doi:10.1097/igc.0000000000001205

Cited by 13 publications

(11 citation statements)

References 36 publications

(70 reference statements)

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“…The recent study by Chen et al, involving 318 patients with high-grade serous ovarian cancer, showed an association between low Ki67 expression and platinum resistance 8. Sallum et al reported no difference in Ki67 expression among patients with platinum-sensitive or platinum-refractory/resistant low-grade and high-grade serous ovarian cancer 14. In contrast, our data show an association between lower Ki67 expression and more frequent TFI of >6 months.…”

Section: Discussioncontrasting

confidence: 74%

Ki67 expression as a predictor of chemotherapy outcome in low-grade serous ovarian cancer

Grabowski¹,

Martinez-Vila²,

Richter³

et al. 2020

Int J Gynecol Cancer

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ObjectiveLow-grade serous ovarian cancers characterize a unique clinical pattern and lower chemotherapy responsiveness. The expression level of Ki67 is associated with differences in prognosis; however, this has not yet been evaluated in regard to predicting the outcome of therapy.MethodsPatients with low-grade serous ovarian cancers were identified in an institutional database. Receiver-operator characteristics (ROC) curve analysis was performed to find cut-off values of Ki67 to discriminate patients with residual tumor mass after surgery from maximal debulked patients: therapy response and therapy-free interval (TFI).ResultsA total of 68 patients with low-grade serous ovarian cancer were identified. All patients underwent surgery. 61 (89.7%) patients received platinum-based first-line chemotherapy; of these 61 patients, 13 (21.3%) had residual mass (>0 mm) after primary cytoreduction and 11 (18%) received neo-adjuvant chemotherapy. Ki67 ≥3.6% was associated with higher risk of residual mass after surgery (OR 8.1, 95% CI 1.45 to 45.18; p=0.017). Patients with Ki67 <3.6% showed a therapy-free interval of ≥6 months more often (OR 13.9, 95% CI 1.62 to 118.40; p=0.016). In the multivariate analysis of TFI <6 months, including CA125, age at diagnosis, peritoneal carcinomatosis, and ascites, Ki67 <3.6% remained a significant prognostic factor (OR 18.8, 95% CI 1.77 to 199.09; p=0.015). Chemotherapy responsiveness was evaluated in 21 patients who had residual disease and/or received neo-adjuvant chemotherapy. Ki67 ≥4.0% (OR 44.1, 95%CI 2.36-825.17, p = 0.011) was related to a significantly higher response rate (complete and partial response).ConclusionsThis is the first study to show an association between Ki67 expression and chemotherapy response, duration of TFI to platinum-based chemotherapy as well as outcome of surgery in low-grade serous ovarian cancers. Further prospective trials should use Ki-67 as a stratification factor to explore the effect of chemotherapy and endocrine strategies.

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Section: Discussioncontrasting

confidence: 74%

Ki67 expression as a predictor of chemotherapy outcome in low-grade serous ovarian cancer

Grabowski¹,

Martinez-Vila²,

Richter³

et al. 2020

Int J Gynecol Cancer

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“…A total of 44 studies were included in this systematic review 10 12 13 18–58. The flow chart outlining the study design is shown in figure 1.…”

Section: Resultsmentioning

confidence: 99%

Immunohistochemistry for the detection of BRCA1 and BRCA2 proteins in patients with ovarian cancer: a systematic review

Teixeira

Reis

2019

J Clin Pathol

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BackgroundLoss of function in either breast cancer type 1 susceptibility protein (BRCA1) or breast cancer type 2 susceptibility protein (BRCA2) is a major risk factor for epithelial ovarian cancer (EOC) development. BRCA1 or BRCA2 deficiencies are associated with short-term prognosis and might have importance for the treatment of women with the disease. However, the screening of all possible mechanisms of dysfunction is expensive, time-consuming and difficult to apply in clinical practice. On the other hand, immunohistochemistry (IHC) is a simple and reliable method to access the expression of several proteins in tumour tissues.Materials and methodsThis systematic review aims to evaluate the current usage of IHC to detect BRCA1 and BRCA2 deficiencies in EOC. We searched and evaluated all primary literature on the use of IHC for evaluating BRCA1 and BRCA2 proteins expression in EOC. The main concepts for the search were: ovarian neoplasms, IHC, BRCA1 and BRCA2.ResultsForty-four studies from 925 unique titles were included. A total of 4206 tumour samples were evaluated for BRCA1 and 1041 for BRCA2 expression. Twelve BRCA1 primary antibodies were used in 41 studies, and the most common was the MS110 clone (75.6%). Seven BRCA2 primary antibodies were used in ten studies. Using the cut-off of 10%, 47.0% of EOCs are associated with loss of BRCA1 and 34.5% with the loss of BRCA2 expression.ConclusionIHC was effective to detect loss of BRCA1 protein expression in EOC; however, data on BRCA2 expression were heterogeneous and difficult to interpret.

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“…LGSC constitutes a smaller group of epithelial ovarian cancer, and are generally treated as the high-grade serous counterpart [7-10,13,17,18]. Gockley et al [19], identified 16,854 (95.7%) patients with high-grade serous ovarian cancer (HGSC) and 755 (4.3%) patients with LGSC from the National Cancer Database [19].…”

Section: Discussionmentioning

confidence: 99%

“…Accumulating data underlined that LGSC are characterized by partial chemoresistance [3-6]. Few studies reported outcomes of patients affected by LGSC and limited data are still available on prognosis of patients affected by advance stage LGSC (stage IIIB–IV) [678910111213].…”

Section: Introductionmentioning

confidence: 99%

The detrimental effect of adopting interval debulking surgery in advanced stage low-grade serous ovarian cancer

et al. 2019

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ObjectiveTo examine outcomes of patients having treatments for newly diagnosed advanced stage low-grade serous ovarian cancer (LGSC).MethodsWe conducted a retrospective case series of women affected by advanced stage (stage IIIB or more) LGSC undergoing surgery in a single oncologic center between January 2000 and December 2017. Survival outcomes were assessed using Kaplan-Meier and Cox models.ResultsData of 72 patients were retrieved. Primary cytoreductive surgery was attempted in 68 (94.4%) patients: 19 (27.9%) had residual disease (RD) >1 cm after primary surgery. Interval debulking surgery (IDS) was attempted in 15 of these 19 (78.9%) patients and the remaining 4 patients having not primary debulking surgery. Twelve out of 19 (63.1%) patients having IDS had RD. After a mean (±standard deviation) follow-up was 61.6 (±37.2) months, 50 (69.4%) and 22 (30.5%) patients recurred and died of disease, respectively. Via multivariate analysis, non-optimal cytoreduction (hazard ratio [HR]=2.79; 95% confidence interval [CI]=1.16–6.70; p=0.021) and International Federation of Obstetrics and Gynecologists (FIGO) stage IV (HR=3.15; 95% CI=1.29–7.66; p=0.011) were associated with worse disease-free survival. Via multivariate analysis, absence of significant comorbidities (HR=0.56; 95% CI=0.29–1.10; p=0.093) and primary instead of IDS (HR=2.95; 95% CI=1.12–7.74; p=0.027) were independently associated with an improved overall survival.ConclusionLGSC is at high risk of early recurrence. However, owing to the indolent nature of the disease, the majority of patients are long-term survivors. Further prospective studies and innovative treatment modalities are warranted to improve patients care.

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BRCA1, Ki67, and β-Catenin Immunoexpression Is Not Related to Differentiation, Platinum Response, or Prognosis in Women With Low- and High-Grade Serous Ovarian Carcinoma

Cited by 13 publications

References 36 publications

Ki67 expression as a predictor of chemotherapy outcome in low-grade serous ovarian cancer

Ki67 expression as a predictor of chemotherapy outcome in low-grade serous ovarian cancer

Immunohistochemistry for the detection of BRCA1 and BRCA2 proteins in patients with ovarian cancer: a systematic review

The detrimental effect of adopting interval debulking surgery in advanced stage low-grade serous ovarian cancer

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