In vivo assessment of the antiproliferative properties of interferon-alpha during immunotherapy: Ki-67 (MIB-1) in patients with metastatic renal cell carcinoma

Abstract

The aim of the present study was to investigate the in vivo antiproliferative effect of interferon alpha (IFN-a) in patients with metastatic renal cell carcinoma (mRCC). Core needle biopsies of metastatic and/or the primary kidney cancer were obtained before interleukin-2 (IL-2)-and IFN-a-based immunotherapy in 34 patients and repeated after 5 weeks in 25 patients. Tumour proliferation was assessed by use of the anti-Ki-67 antibody MIB-1 and evaluated in multiple, random systematic sampled fields of vision. Ki-67 labelling index (LI) at baseline was median 13.6% (range 1.2 -85.0) and median 10.6% (range 1.3 -48.6%) at week 5 with a median overall decline of 15.2% (range À95 to þ 258%) from baseline to week 5. There was no difference between responding and nonresponding patients. Ki-67 LI at week 5 was significantly correlated to survival. Thus, median survival of patients with Ki-67 LI p10.6% at week 5 was 25.1 months compared to 11.5 months for patients with Ki-67 LI 410.6% (P ¼ 0.016). Baseline or change in Ki-67 LI did not correlate to survival. These data suggest that IFN-a in vivo has only modest effect on tumour proliferation in patients with mRCC. Tumour Ki-67 (MIB-1) reactivity after 1 month of immunotherapy appears to be a significant predictor of patient survival.

Extremely Long Survival under Combined Immunotherapy in a Metastatic Functional Neuroendocrine Neoplasia Patient

“…5). The proliferation changed from 5% initially to 80% in 2014, whereas in the last years, during treatment with immunotherapy Ki-67 reversed from 80 to 40%, an observation previously made also by others [31]. In addition, the case demonstrates that upon dedifferentiation, functionality is lost since the patient did not present with flushing later on, leading to a cessation of octreotide treatment.…”

“…This is the first reported case concerning an objective, long-lasting therapeutic tumor response using immunotherapy in an NET patient and it is also the first report about a successful combination of vaccination together with PD-1 and CTLA-4 blockade in NET patients [31]. It is especially of note that the combination of temozolomide and capecitabine plus ipilimumab (CTLA-4) led to a complete remission, i.e., that a combination of chemotherapy plus immunotherapy might lead to an improved therapeutic response.…”

Mcm2, Geminin, and KI67 Define Proliferative State and are Prognostic Markers in Renal Cell Carcinoma

“…Furthermore, the effect of immunotherapy upon origin licensing in metastatic RCC could provide a valuable predictor of disease response. This approach has already been taken in a study assessing proliferative response using Ki67 antibody (50). However, whereas Donskov et al (50) found that Ki67 was a prognostic factor, Ki67 response to immunotherapy did not identify treatment responders.…”

“…This approach has already been taken in a study assessing proliferative response using Ki67 antibody (50). However, whereas Donskov et al (50) found that Ki67 was a prognostic factor, Ki67 response to immunotherapy did not identify treatment responders. Here we have shown that Mcm2 is a much more sensitive growth marker than Ki67 in RCC; thus, the antiproliferative effect of immunotherapy may be more easily measured using Mcm2.…”

Prognostic Factors in Renal Cell Carcinoma: An Evaluation of T-Stage, Histopathological Grade, p53, Ki-67, COX-2, and Her-2 Expressions

“…Kaplan-Meier survival curve for p53 in mRCC (n=66) (Kankuri et al 2006). Dudderidge et al (2005) found Ki-67 to be an independent prognostic factor for disease-free survival in nephrectomized RCC, but opposite results have also been published (Donskov et al 2004, Kim et al 2004, Yildiz et al 2004. No association between Ki-67 alone and survival in locally confined RCC patients was found in the study of Kankuri et al (2006).…”