The Genomics and Biomarkers Program, The John Theurer Cancer Center, Hackensack University Medical Center, Hackensack Meridian Health, Hackensack, NJ 07601, USA.
Biostatistics, Department of Research, Hackensack University Medical Center, Hackensack Meridian Health, Hackensack, NJ 07601, USA.
Breast. 2018 Jun;39:101-109. doi: 10.1016/j.breast.2018.03.015. Epub 2018 Apr 12.
Breast cancer (BC) is the second leading cause of cancer-related mortality in women. Bioinformatic analysis and expression screening showed that Prolactin Induced Protein (PIP) was differentially expressed in BC. The objective of this investigation was to characterize the expression pattern of PIP, an aspartyl proteinase, in malignant and non-malignant breast tissues.
Real time quantitative PCR was employed to analyze PIP and androgen receptor (AR) mRNA levels in BC cell lines and 190 normal tissues and tumor samples. The tumor specimens were categorized based on TNM classification, anatomic stage, histologic grade and molecular subtype and expression pattern evaluated. To detect protein levels, immunohistochemistry followed by semi quantitative scoring was employed in the examination of 517 normal, benign, and invasive BC tissues.
We observed substantial downregulation of PIP transcription in cancer samples compared to normal breast tissue. mRNA levels were significantly downregulated (93 fold, P < 0.005) in advanced grades compared to lower grades. Transcript levels were also significantly lower (22 fold, P < 0.05) in triple negative tumors compared to hormone receptor positive tumors. Significant downregulation was observed in early stage samples of triple negative and hormone receptor positive tumors. Though PIP protein showed a wide range of expression levels in BC, early stage samples showed significant downregulation.
PIP mRNA is significantly downregulated in early stage BC compared to normal breast tissue. Consequently, low PIP mRNA expression in BC tissues could potentially be used as a tissue based biomarker to assist pathologists in confirmation of early stage BC diagnosis.
乳腺癌（BC）是女性癌症相关死亡的第二大主要原因。生物信息学分析和表达筛选显示，泌乳素诱导蛋白（PIP）在 BC 中差异表达。本研究的目的是描述天冬氨酸蛋白酶 PIP 在恶性和非恶性乳腺组织中的表达模式。
采用实时定量 PCR 分析 BC 细胞系和 190 例正常组织和肿瘤样本中的 PIP 和雄激素受体（AR）mRNA 水平。根据 TNM 分类、解剖分期、组织学分级和分子亚型对肿瘤标本进行分类，并评估表达模式。为了检测蛋白水平，采用免疫组织化学法结合半定量评分法检测 517 例正常、良性和浸润性 BC 组织。
与正常乳腺组织相比，我们观察到癌症样本中 PIP 的转录显著下调。与低分级相比，高级别肿瘤样本的 mRNA 水平显著下调（93 倍，P<0.005）。与激素受体阳性肿瘤相比，三阴性肿瘤的转录水平也显著降低（22 倍，P<0.05）。三阴性和激素受体阳性肿瘤的早期阶段样本也观察到显著下调。尽管 PIP 蛋白在 BC 中表现出广泛的表达水平，但早期阶段样本显示出显著下调。
与正常乳腺组织相比，早期 BC 中 PIP mRNA 显著下调。因此，BC 组织中低水平的 PIP mRNA 表达可能可作为组织生物标志物，协助病理学家确认早期 BC 的诊断。
