Department of Pathology, Stavanger University Hospital, Stavanger, Norway.
Department of Mathematics and Natural Science, University of Stavanger, Stavanger, Norway.
PLoS One. 2020 Jun 2;15(6):e0233676. doi: 10.1371/journal.pone.0233676. eCollection 2020.
In urothelial cell type non-muscle invasive urinary bladder carcinoma, TNM stage and WHO grade are widely used to classify patients into low and high‑risk groups for prognostic and therapeutic decision-making. However, stage and grade reproducibility and prediction accuracy are wanting. This may lead to suboptimal treatment. We evaluated whether proliferation features, nuclear area of the epithelial cancer cells and the composition of stromal and tumor infiltrating lymphocytes have independent prognostic value. In 183 primary non-muscle invasive bladder cancer patients with long follow-up (median for stage progression cohort: 119 months, range 5-173; median for tumor recurrence cohort: 82, range 3-165) proliferation features Ki67, PPH3 and Mitotic Activity Index (MAI), Mean Nuclear Area (MNA), lymphocyte subsets (CD8+, CD4+, CD25+) and plasma cells (CD138+) were assessed on consecutive sections. Post-resection instillation treatments (none, mitomycin, BCG) were strictly standardized during the intake period. Risk of recurrence was associated with expression of Ki67 (≤ 39 vs. > 39) and Multifocality (p = 0.01). Patients with low Ki67 had a higher recurrence rate than those with high Ki67. Lymphocyte composition did not predict recurrence. Stage progression was strongly associated with high values for MAI (>15) and CD25+ (>0.2%). In a multivariate analysis the combination of MAI and CD25+ was the single most prognostic feature (p<0.001). Validation of these results in additional, independent studies is warranted.
在尿路上皮细胞型非肌肉浸润性膀胱癌中,TNM 分期和 WHO 分级广泛用于将患者分为低风险和高风险组,以进行预后和治疗决策。然而,分期和分级的可重复性和预测准确性并不理想。这可能导致治疗不当。我们评估了增殖特征、上皮癌细胞的核面积以及基质和肿瘤浸润淋巴细胞的组成是否具有独立的预后价值。在 183 例具有长期随访的原发性非肌肉浸润性膀胱癌患者中(进展队列的分期中位数:119 个月,范围 5-173;肿瘤复发队列的中位数:82 个月,范围 3-165),在连续切片上评估了增殖标志物 Ki67、PPH3 和有丝分裂活动指数(MAI)、平均核面积(MNA)、淋巴细胞亚群(CD8+、CD4+、CD25+)和浆细胞(CD138+)。在纳入期严格标准化了术后膀胱灌注治疗(无治疗、丝裂霉素、BCG)。复发风险与 Ki67 的表达(≤39 与>39)和多灶性(p=0.01)相关。Ki67 低表达的患者比 Ki67 高表达的患者有更高的复发率。淋巴细胞组成与复发无关。进展期与高 MAI(>15)和 CD25+(>0.2%)值密切相关。在多变量分析中,MAI 和 CD25+的组合是唯一最具预后特征的因素(p<0.001)。需要在其他独立研究中验证这些结果。
Mod Pathol. 2017-12-1
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