Jeong Se Un, Kekatpure Anuja Kashikar, Park Ja-Min, Han Minkyu, Hwang Hee Sang, Jeong Hui Jeong, Go Heounjeong, Cho Yong Mee
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
J Pathol Transl Med. 2017 Sep;51(5):471-481. doi: 10.4132/jptm.2017.06.02. Epub 2017 Aug 9.
Ductal adenocarcinoma (DAC) of the prostate is an uncommon histologic subtype whose prognostic factors and immunoprofile have not been fully defined.
To define its prognostic factors and immunoprofile, the clinicopathological features, including biochemical recurrence (BCR), of 61 cases of DAC were analyzed. Immunohistochemistry was performed on tissue microarray constructs to assess the expression of prostate cancer-related and mammalian target of rapamycin (mTOR) signaling-related proteins.
During the median follow-up period of 19.3 months, BCR occurred in 26 cases (42.6%). DAC demonstrated a wide expression range of prostate cancer-related proteins, including nine cases (14.8%) that were totally negative for pan-cytokeratin (PanCK) immunostaining. The mTOR signaling-related proteins also showed diverse expression. On univariate analysis, BCR was associated with high preoperative serum levels of prostate-specific antigen (PSA), large tumor volume, predominant ductal component, high Gleason score (GS), comedo-necrosis, high tumor stage (pT), lymphovascular invasion, and positive surgical margin. High expressions of phospho-mTOR (p-mTOR) as well as low expressions of PSA, phospho-S6 ribosomal protein (pS6) and PanCK were associated with BCR. On multivariable analysis, GS, pT, and immunohistochemical expressions of PanCK and p-mTOR remained independent prognostic factors for BCR.
These results suggest GS, pT, and immunohistochemical expressions of PanCK and p-mTOR as independent prognostic factors for BCR in DAC. Since DAC showed diverse expression of prostate cancer-related proteins, this should be recognized in interpreting the immunoprofile of DAC. The diverse expression of mTOR-related proteins implicates their potential utility as predictive markers for mTOR targeted therapy.
前列腺导管腺癌（DAC）是一种罕见的组织学亚型，其预后因素和免疫表型尚未完全明确。
为了明确其预后因素和免疫表型，分析了61例DAC患者的临床病理特征，包括生化复发（BCR）情况。对组织微阵列构建体进行免疫组织化学检测，以评估前列腺癌相关蛋白和雷帕霉素哺乳动物靶蛋白（mTOR）信号相关蛋白的表达。
在中位随访期19.3个月内，26例（42.6%）出现BCR。DAC显示出前列腺癌相关蛋白的广泛表达范围，包括9例（14.8%）全细胞角蛋白（PanCK）免疫染色完全阴性。mTOR信号相关蛋白也表现出不同的表达。单因素分析显示，BCR与术前血清前列腺特异性抗原（PSA）水平高、肿瘤体积大、主要为导管成分、高Gleason评分（GS）、粉刺样坏死、高肿瘤分期（pT）、淋巴管浸润和手术切缘阳性有关。磷酸化mTOR（p-mTOR）高表达以及PSA、磷酸化S6核糖体蛋白（pS6）和PanCK低表达与BCR相关。多因素分析显示，GS、pT以及PanCK和p-mTOR的免疫组化表达仍然是BCR的独立预后因素。
这些结果表明，GS、pT以及PanCK和p-mTOR的免疫组化表达是DAC中BCR的独立预后因素。由于DAC显示出前列腺癌相关蛋白的多样化表达，在解释DAC的免疫表型时应予以认识。mTOR相关蛋白的多样化表达暗示了它们作为mTOR靶向治疗预测标志物的潜在效用。
