KI-67 and Recurrence in Pituitary Adenomas: A Systematic Review

Background: K_i-67 is a marker of cellular proliferation that has been studied in clinical and pathological parameters of pituitary adenomas. The assessment of K_i-67 expression has shown utility in the evaluation of pituitary adenomas and predicting their invasiveness. Studies have shown variable results with K_i-67's correlation to recurrence. The purpose of this study is to determine if a high K_i-67 index is predictive of recurrence in pituitary adenomas.

Methods: Systemic data searches were performed in PubMed-NCBI and Cochrane by an academic librarian through September 2019. No restrictions based on year of publication were used. Inclusion criteria comprised of studies that reported K_i-67 indices, recurrence rate for pituitary adenomas, and a follow-up time reported. Studies reporting K_i-67 and pituitary carcinoma were excluded. Two independent reviewers screened each abstract and full text article. Additional data from our institution was included as well. Demographics, tumor characteristics, treatment course, and recurrence data were collected from each article. Assessment of quality and bias was evaluated according to the NIH. Analyses were performed using SAS version 9.4 (SAS Institute, Cary, NC) and forest plots were created using R version 4.0.2 (R Foundation for Statistical Computing).

Results: Of 244 articles identified, 50 were assessed for eligibility based on inclusion criteria and 30 were included for analysis. The median study sample size was 51 (IQR: 35–117; Range: 5–566), most reported a mean patient age between 40 and 50 years, and most studies featured equal representation by sex. Only 8 studies reported tumor size (median size: 26 mm, IQR: 22–31). Eighteen studies reported recurrence by level of ki-67: 1 study used a threshold of 1%, 13 studies used 3%, 1 study used 5%, and 3 studies reported based on other levels. Among studies that compared ki-67 ≥ 3 vs. < 3%, 10 studies reported odds ratios greater than 1, of which 6 were statistically significant. Compared with those with ki-67 < 3%, those with ki-67 ≥ 3% had higher odds of recurrence via the pooled odds ratio (OR = 4.15, 95% CI: 2.31–7.42 in Image 1). These studies featured significant heterogeneity (Q = 23.8, p = 0.02), and the funnel plot was asymmetrical with a skew toward a positive effect.

Conclusion: K_i-67 values of >3% had higher odds of recurrence compared with those tumors with K_i-67 values <3%. This systematic review gives valuable information regarding the prognostic value of K_i-67 as a marker for recurrence in pituitary adenomas.