Laboratory of Mutagenesis and Oncogenetics, Department of General Biology, Londrina State University, Londrina, PR, Brazil.
Laboratory of Extracellular Matrix, Department of General Biology, Londrina State University, Londrina, PR, Brazil.
J Cancer Res Clin Oncol. 2023 Feb;149(2):567-577. doi: 10.1007/s00432-022-04274-w. Epub 2022 Aug 25.
Prostate cancer (PCa) lacks specific markers capable of distinguishing aggressive tumors from those with indolent behavior. Therefore, the aim of this study was to evaluate the immunostaining of candidate proteins (PTEN, AKT, TRPM8, and NKX3.1) through the immunohistochemistry technique (IHC) on patients with metastatic and non-metastatic PCa.
Tissues from 60 patients were divided into three groups categorized according to prognostic parameters: better prognosis (n = 20), worse prognosis (n = 23), and metastatic (n = 17). Immunostaining was analyzed by a pathologist and staining classifications were considered according to signal intensity: (0) no staining, (+) weak, and (++ and +++) intermediate to strong.
AKT protein was associated (p = 0.012) and correlated (p = 0.014; Tau = - 0.288) with the prognostic groups. The immunostaining for TRPM8 (p = 0.010) and NKX3.1 (p = 0.003) proteins differed between malignant tumor and non-tumoral adjacent tissue as well as for proteins in cellular locations (nucleus and cytoplasm). TRPM8 was independently associated with the ISUP grade ≥ 4 (p = 0.024; OR = 8.373; 95% CI = 1.319-53.164). The NKX3.1 showed positive and predominantly strong immunostaining in all patients in both tumoral and non-tumoral adjacent tissues. All metastatic samples had positive immunostaining, with strong intensity for NKX3.1 (p = 0.021; Tau = - 0.302). In the non-metastatic group, this strong protein staining was not observed in any patients.
This study confirmed that NKX3.1 is highly specific for prostate tissue and indicated that NKX3.1, AKT, and TRPM8 may be candidate markers for prostate cancer prognosis.
前列腺癌（PCa）缺乏能够区分侵袭性肿瘤和惰性行为肿瘤的特定标志物。因此，本研究旨在通过免疫组织化学技术（IHC）评估候选蛋白（PTEN、AKT、TRPM8 和 NKX3.1）的免疫染色在转移性和非转移性 PCa 患者中的应用。
将 60 例患者的组织分为三组，根据预后参数进行分类：预后较好组（n=20）、预后较差组（n=23）和转移性组（n=17）。由病理学家进行免疫染色分析，并根据信号强度对染色分类进行考虑：（0）无染色、（+）弱和（++和+++）中到强。
AKT 蛋白与预后组相关（p=0.012）且具有相关性（p=0.014；Tau=-0.288）。TRPM8 和 NKX3.1 蛋白的免疫染色在恶性肿瘤和非肿瘤相邻组织之间以及细胞位置（核和细胞质）之间存在差异。TRPM8 与 ISUP 分级≥4 独立相关（p=0.024；OR=8.373；95%CI=1.319-53.164）。NKX3.1 在所有肿瘤和非肿瘤相邻组织的患者中均表现出阳性和强染色。所有转移性样本均具有 NKX3.1 的阳性免疫染色，且强度较强（p=0.021；Tau=-0.302）。在非转移性组中，没有患者出现这种强蛋白染色。
本研究证实 NKX3.1 对前列腺组织具有高度特异性，并表明 NKX3.1、AKT 和 TRPM8 可能是前列腺癌预后的候选标志物。
