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Loss of expression of protein tyrosine kinase 7 in invasive ductal breast cancers.

ABSTRACT: Protein tyrosine kinase 7 (PTK7) is a catalytically inactive receptor tyrosine kinase that is involved in development and tumorigenesis. PTK7 expression and its functional roles have been investigated in several human cancers, although controversial results have been obtained. In this study, we investigated the expression of PTK7 protein in invasive ductal breast cancer tissues, and analyzed its relationship with clinicopathologic parameters. Seventy-nine consecutive invasive breast cancer tissues were included in the study, and PTK7 protein was detected in invasive ductal breast cancers and normal breast epithelial cells by immunohistochemistry. Positive staining was noted in all normal breast epithelial cells and differential expression was observed in breast carcinomas. Thirty-eight of 79 samples (48.1%) were negative or stained weakly for PTK7 (-), 19 (24.1%) showed moderate staining (+), and 22 (27.8%) were strongly stained (++). PTK7 expression was negatively associated with tumor grade (P=0.025, r=-0.251), tumor-node-metastasis stage (P=0.004, r=-0.317), lymph node metastasis (P=0.002, r=-0.351), human epidermal growth factor receptor 2 expression (P=0.029, r=-0.245), and Ki67 expression (P=0.004, r=-0.317), and positively associated with estrogen receptor (ER) expression (P=0.037, r=0.235). No significant relationship was found between PTK7 expression and patient age or progesterone receptor (PR) expression. Our data indicated that PTK7 protein was down-regulated in breast cancer cells compared with healthy epithelial cells, and that PTK7 may be a tumor suppressor gene in breast cancer. Future studies should explore the molecular mechanisms underlying the down-regulation and functional roles of PTK7 in breast cancer.

SUBMITTER: Sun J

PROVIDER: S-EPMC6945173 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Loss of expression of protein tyrosine kinase 7 in invasive ductal breast cancers.

Sun Jingjun J Zhou Qi Q Tao Yumei Y Chen Jianxin J Wang Jiandong J

International journal of clinical and experimental pathology 20190301 3

Protein tyrosine kinase 7 (PTK7) is a catalytically inactive receptor tyrosine kinase that is involved in development and tumorigenesis. PTK7 expression and its functional roles have been investigated in several human cancers, although controversial results have been obtained. In this study, we investigated the expression of PTK7 protein in invasive ductal breast cancer tissues, and analyzed its relationship with clinicopathologic parameters. Seventy-nine consecutive invasive breast cancer tissu ...[more]

PMID: 31933919

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Project description:BackgroundReceptor tyrosine kinases (RTKs) are a class of tyrosine kinases that regulate cell-to-cell communication and control a variety of complex biological functions. Dysregulation of RTK signaling partly due to chromosomal rearrangements leads to novel tyrosine kinase fusion oncoproteins that are possibly driver alterations to cancers. Targeting some RTK fusions with specific tyrosine kinases inhibitors (TKIs) is an effective therapeutic strategy across a spectrum of RTK fusion-related cancers. However, there is still a paucity of extensive RTK fusion investigations in breast cancer. This study aims to characterize RTK fusions in Chinese breast cancer patients.MethodsAn in-house DNA sequencing database of 1440 Chinese breast cancer patients with a capture-based panel (520 gene or 108 gene-panel) was thoroughly reviewed. A total of 2,229 samples including 1,045 tissues and 1,184 plasmas were analyzed. RTK fusion was defined as an in-frame fusion with the tyrosine kinase domain of the RTK completely retained. Concomitant mutations were also analyzed and tumor mutational burden (TMB) was calculated. Patients' clinical characteristics were retrieved from case records.ResultsA total of 30 RTK fusion events were identified from 27 breast cancer patients with a prevalence of 1.875%%. FGFR2 fusions were seen the most commonly (n=7), followed by RET (n=5), ROS1 (n=3), NTRK3 (n=3), BRAF (n=2), and NTRK1 (n=2). Other RTK fusions including ALK, EGFR, FGFR1, FGFR3, MET, and NTRK2 were identified in one patient each. A total of 27 unique resultant fusion proteins (22 with a novel partner) were discovered including 19 intrachromosomal rearrangements and 8 interchromosomal ones. Twenty-one fusions had the tyrosine kinase domain in-frame fused with a partner gene and six were juxtaposed with an intergenic space. Among the 27 fusions, FGFR2-WDR11 (E17: intergenic) (n=3) and ETV6-NTRK3 (E5:E15) (n=2) occurred recurrently. Of note, the normalized abundance of RTK fusion (fusion AF/max AF) correlated negatively with TMB (r=-0.48, P=0.017). Patients with TMB < 8 (Mutations/Mb) displayed a higher fusion abundance than those with TMB ≥ 8 (Mutations/Mb) (P=0.025). Moreover, CREBBP mutation only co-occurred with FGFR2 fusion (P=0.012), while NTRK3 fusion and TP53 mutation were mutually exclusive (P=0.019).ConclusionThis is the first study comprehensively delineating the prevalence and spectrum of RTK fusions in Chinese breast cancers. Further study is ongoing to identify the enriched subpopulation who may benefit from RTK fusion inhibitors.

Project description:BackgroundThe breast cancer is the most prevalent cancer among women, on the other hand absence of myoepithelial cells play a pivotal role in pathogenesis of this cancer. Thus we aimed to investigate the possible abilities of the molecular assay technique to find a relationship between mammary serine protease inhibitor (Maspin) gene expression possibly secreted by myoepithelial cells, grade of breast cancer and other prognostics factors (ER, PR, and c-erb-B2).MethodsParaffin embedded blocks of 31 breast cancer patients together with two normal breast tissues were used for IHC staining and Maspin gene RNA detection uses the real-time PCR method. Applying QIAGEN kit, we were able to measure Maspin RNA and Extract the cDNA of different samples for evaluating the Maspin RNA level.ResultsWe found that the RNA level was considerably lowerin these cancer samples compared with normal samples. In addition, different grades of breast cancer in the obtained results adopt some distinguishable values. The Maspin expression in samples with grades II and III is much lower than the ones in normal group (P<0.05) which could be considered as a promising way in diagnosing of this disease. The results showed no considerable differences in Maspin gene expression of the c-erb-B2 scores in the tumor group except the samples having score 0. The other observation of this research study confirmed that Maspin gene expression couldn't show any differences between the values of both ER and PR in different scores of the tumor group. On the other hand, the cDNA of these patients showed lower values compared with normal samples.ConclusionMaspin expression was reduced in samples with grade II& III of invasive ductal carcinoma. Based on expression of Maspin Inc-erb-B2, it seems that more expression happened in normal group comparing with different scores of it. We could suggest that there was a reverse relationship between tumor formation and Maspin gene expression. These results showed possible role of Maspin as prognostic factor.

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Loss of expression of protein tyrosine kinase 7 in invasive ductal breast cancers.

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Loss of expression of protein tyrosine kinase 7 in invasive ductal breast cancers.

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