Association of quantitative assessment of the intrafollicular proliferation index with outcome in follicular lymphoma

Abstract

SummaryThe role of the proliferation index (PI) as an outcome predictor in follicular lymphoma (FL) isn't clear. We have previously demonstrated that quantitative image analysis (QIA) is a robust tool for PI determination and the present study aimed to determine the significance of the PI for outcome in low-grade FL. One hundred and twenty-nine patients with grade 1-2 FL were retrospectively analysed. Slides were scanned digitally and follicle/ tumour-involved areas were annotated. The intrafollicular PI was estimated by analysing a median of 10 follicles per case. Patients were divided into two groups: PI < 30%, PI ≥ 30% and clinical outcome was analysed. Among the 129 patients analysed, intrafollicular PI ranged from 0Á6 to 63Á2% with a median of 23Á3%. Overall survival was not influenced by PI group. Among those patients initially observed, intrafollicular PI < 30% was associated with longer time to first therapy compared to patients with a PI ≥ 30%. In the group of patients that were treated at diagnosis, PI was not predictive of time to treatment failure (TTTF). Intrafollicular PI is an important predicator of TTFT for patients who are candidates for observation. Further confirmation in an independent cohort of patients is necessary to determine the clinical validity of the results.

Prognostic significance of histologic grade and Ki‐67 proliferation index in follicular lymphoma

“…predicted an inferior outcome, although various cut-off values ranged from 10% to 30%. 9,14,15 We confirmed the results of previous studies that increasing Ki-67 positivity correlated with higher histologic grades and was significantly different between grades 1, 2 and 3. 5,12,22 Furthermore, Mercadal et al 12 observed a trend towards better PFS in FL 3A patients compared with FL 1-2 patients who received cumulative R therapy; moreover, the proportion of cases of higher Ki-67 (>50%) was significantly higher in FL 3A patients than in FL 1-2 patients.…”

“…In addition, a considerable amount of literature has demonstrated that the Ki-67 proliferation index was a predictive factor for the outcome of FL. 4,6,9,14,15 These studies consistently reported that higher Ki-67 was associated with inferior prognosis, although the cut-off values varied.…”

“…Furthermore, Nabhan et al 13 investigated the prognosis of FL in different races in a large scale study, finding that there was no statistically significant improvement in outcome for Asian/Pacific Islanders after the prevalence of R. Thus, the impact of race on the survival of FL patients does exist. In addition, a considerable amount of literature has demonstrated that the Ki‐67 proliferation index was a predictive factor for the outcome of FL 4,6,9,14,15 . These studies consistently reported that higher Ki‐67 was associated with inferior prognosis, although the cut‐off values varied.…”

Differential expression of long non‐coding RNAs are related to proliferation and histological diversity in follicular lymphomas

“…Noticeably, 12 different biological processes were significantly different between the studied FL groups, with cell cycle (higher in FL3B/DLBCL) and signal transduction (higher in FL1‐3A) reaching the highest statistical significance (Fig ) (Table SVII). Interestingly, cell proliferation is a relevant deregulated process with clinical impact in FL (Janikova et al , ; Samols et al , ; Kedmi et al , ). Our results suggested that changes in lncRNA expression between FL histological subgroups could contribute in part to the differential biological and clinical features by modulating the expression of proliferation‐related genes.…”

“…This finding suggests that lncRNA deregulation in FL3B/DLBCL may represent a molecular mechanism associated with increased proliferation in FL. This is noticeable as FL3B and DLBCL have higher proliferation than the low grade tumours and proliferation may have prognostic impact in FL independently of the histological grade (Janikova et al , ; Samols et al , ; Kedmi et al , ). Interestingly, a number of lncRNA have been also related to cell proliferation in the context of normal B‐cell differentiation, where a subset of lncRNAs were associated with the expression of cell cycle regulatory genes in pre B1/B2 cells and centroblasts, two highly proliferative compartments of the B‐cell differentiation process (Petri et al , ).…”