Hommerding Oliver, Bernhardt Marit, Kreft Tobias, Scherping Anna, Abbas Mahmoud, Baretton Gustavo, Bräsen Jan Hinrich, Breyer Johannes, Darr Christopher, Dressler Franz Friedrich, Ellinger Jörg, Erber Ramona, Esposito Irene, Hartmann Arndt, Hartmann Wolfgang, Heitplatz Barbara, Kreipe Hans, Lafos Marcel, Linxweiler Johannes, Lopez-Cotarelo Cristina, Sailer Verena, Reis Henning, Saar Matthias, Schildhaus Hans-Ulrich, Schlack Katrin, Schmid Matthias, Seidl Maximilian, Semjonow Axel, Sommer Ulrich, Stahl Phillip Rolf, Tischler Verena, Weber Florian, Wulf Anna-Lena, Wullich Bernd, Kristiansen Glen
Institute of Pathology, University Hospital Bonn, Bonn, Germany.
Institute of Pathology, University Hospital Muenster, Muenster, Germany.
Virchows Arch. 2024 Dec 9. doi: 10.1007/s00428-024-03999-y.
The prognostication of individual disease trajectory and selection of optimal therapy in patients with localized, low-grade prostate cancer often presents significant difficulty. The phosphatase and tensin homolog on chromosome 10 (PTEN) has emerged as a potential novel biomarker in this clinical context, based on its demonstrated prognostic significance in multiple retrospective studies. Incorporation into standard clinical practice necessitates exceptional diagnostic accuracy, and PTEN's binary readout-retention or loss-suggests its suitability as a biomarker. This multi-institutional ring trial aimed to validate the diagnostic precision of PTEN immunohistochemistry in localized, low- to intermediate-risk prostate cancer, across ten university pathology institutes in Germany. The trial incorporated 90 cases of patients diagnosed with acinar adenocarcinoma of the prostate of grade groups 1 (n = 8, 8.9%) and 2 (n = 82, 91.1%) post-radical prostatectomy. Remarkably, the interpretation of PTEN immunohistochemistry displayed substantial variation (12.5-51.2% PTEN loss rates) within an identical cohort of prostate cancer. Fluorescence in situ hybridization analysis demonstrated PTEN hemizygous deletions in 5.5% (5/90) of cases. All cases with hemizygous deletions presented a distinct loss of PTEN expression by immunohistochemistry and were unanimously identified as PTEN loss by all participants (sensitivity 100%). However, negative (loss) immunohistochemistry was relatively non-specific for an underlying genomic deletion. Improved inter-observer agreement was observed in a subsequent ring trial. Finally, we identify S473-pAKT immunohistochemistry as a useful marker in equivocal cases. In summary, this multi-institutional ring trial illustrates surprisingly heterogeneous outcomes in defining PTEN status by immunohistochemistry.
对于局限性、低级别前列腺癌患者，预测个体疾病轨迹并选择最佳治疗方案往往极具难度。基于多项回顾性研究中所证实的预后意义，10号染色体上的磷酸酶和张力蛋白同源物（PTEN）已成为这一临床背景下一种潜在的新型生物标志物。将其纳入标准临床实践需要极高的诊断准确性，而PTEN的二元读数——保留或缺失——表明它适合作为一种生物标志物。这项多机构环形试验旨在验证德国十所大学病理研究所中PTEN免疫组化在局限性、低至中危前列腺癌中的诊断准确性。该试验纳入了90例在根治性前列腺切除术后被诊断为1级（n = 8，8.9%）和2级（n = 82，91.1%）腺泡腺癌的患者。值得注意的是，在同一组前列腺癌患者中，PTEN免疫组化的解读存在显著差异（PTEN缺失率为12.5 - 51.2%）。荧光原位杂交分析显示5.5%（5/90）的病例存在PTEN半合子缺失。所有半合子缺失的病例通过免疫组化均呈现出明显的PTEN表达缺失，且所有参与者一致将其判定为PTEN缺失（敏感性100%）。然而，免疫组化阴性（缺失）对于潜在的基因组缺失相对缺乏特异性。在随后的环形试验中观察到观察者间一致性有所提高。最后，我们确定S473 - pAKT免疫组化是可疑病例中的一个有用标志物。总之，这项多机构环形试验表明，通过免疫组化定义PTEN状态时，结果存在惊人的异质性。
