Impact of Ki-67 Labeling Index on Prognostic Significance of the Chemotherapy Response Score in Women With Tubo-ovarian Cancer Treated With Neoadjuvant Chemotherapy

Abstract

The chemotherapy response score (CRS) proposed by Bohm and colleagues in 2015 has been validated as a reproducible method for determining histopathologic response of tubo-ovarian carcinoma to neoadjuvant chemotherapy and stratifies tumor response into 3 groups: CRS1 is defined as minimal/no response, CRS2 as moderate response, and CRS3 as marked response. Although described as a 3-tiered system, it essentially works as a 2-tiered system (CRS1/CRS2 vs. CRS3) for assessing prognosis. Here, we analyzed the prognostic value of CRS in a large cohort of tubo-ovarian carcinomas at a tertiary care center and evaluated the potential for Ki-67 labeling index on post-neoadjuvant chemotherapy samples to provide additional prognostic information. We included 170 patients with tubo-ovarian carcinoma treated with neoadjuvant chemotherapy followed by interval debulking surgery. We determined CRS for each case by reviewing slides from the interval debulking surgery resection specimen and calculated progression-free survival and overall survival. For each case with residual disease (CRS1 and CRS2, n = 123, 72%), we also performed Ki-67 antibody staining and determined both average and highest Ki-67 labeling index. Consistent with prior studies, patients in our cohort with CRS1 and CRS2 showed significantly shorter progression-free survival and overall survival compared with CRS3. Further, in the subset of cases with CRS1 and CRS2, Ki-67 labeling index was predictive of OS at multiple cutoff points. An average Ki-67 labeling index of 20% (log rank test P-value: 0.0004) or a highest Ki-67 labeling index of 50% (log rank test P-value: 0.0002) could provide a practically useful cutoff. Multivariable cox proportional hazard model showed worse overall survival with both, average Ki-67 > 20% (hazard ratios: 2.02, P-value: 0.00422, confidence interval: 1.25-3.28) and highest Ki-67 > 50% (hazard ratios: 1.88, P-value: 0.0205, confidence interval: 1.1-3.2). We propose adding Ki-67 labeling index to CRS to provide additional prognostic separation between patients with CRS1 and CRS2.

High-Expression of Cytoplasmic Poly (A) Binding Protein 1 (PABPC1) as a Prognostic Biomarker for Early-Stage Esophageal Squamous Cell Carcinoma

“…Expression of the Ki-67 protein, a well-established marker of proliferation during G1 and S phases, was used to detect the malignant growth of epithelial tumor cells. [18][19][20] Ki-67 index of the normal esophageal epithelium was lower than that of ESCC, and that of dysplasia 21 In the present study, positive Ki-67 immunostaining was presented in all the 231 ESCC cases; however, no positive immunostaining was detected in paired normal tissues, indicating that increased proliferative activity in ESCC cells. However, no statistical significance for OS was observed between ESCC patients with high Ki-67 index and low Ki-67 index in this study.…”

Expression and clinical significance of Ki-67 and P16 after neoadjuvant chemotherapy for locally advanced cervical cancer

“…Univariate and multifactorial Cox regression analyses showed that Ki-67 and lymphovascular space invasion were independent risk factors for the recurrence of stage IB2 and IIA2 cervical cancer and, more importantly, survival analyses suggested that patients with high ki-67 expression levels had lower recurrence-free survival and overall survival rates compared to those with low ki-67 expression levels. Gunter von Minckwitz G et al [22]and another study on ovarian cancer [23] also showed that high levels of Ki-67 after treatment helped to identify patients at high risk of recurrence; Ki-67 levels after neoadjuvant chemotherapy appeared to be more important and more re ective of patient prognosis than changes in Ki-67 levels due to treatment, both suggesting that high levels of Ki-67 after neoadjuvant chemotherapy are associated with poor patient prognosis. This study also showed that high levels of ki-67 expression after neoadjuvant chemotherapy were associated with poorer relapse-free survival (p = 0.001) and overall survival (p = 0.036), which is consistent with most of the studies mentioned above.…”