Solitary fibrous tumors (SFTs) are
NAB2
-
STAT6
fusion-associated neoplasms. There are several subtypes of
NAB2-STAT6
fusions, but their clinical significances are still unclear. Moreover, the ...mechanisms of malignant progression are also poorly understood. In this study, using 91 SFT cases, we examined whether fusion variants are associated with clinicopathological parameters and also investigated the molecular mechanism of malignant transformation using whole-exome sequencing. We detected variant 1b (
NAB2
ex4-
STAT6
ex2) in 51/91 (56%) cases and variants 2a/2b (
NAB2
ex6-
STAT6
ex16/17) in 17/91 (19%) cases. The
NAB2-STAT6
fusion variant types were significantly associated with their primary site (
P
< 0.001). In addition, a
TERT
promoter mutation was detected in 7/73 (10%) cases, and it showed a significant association with malignant SFTs (
P
= 0.003). To identify molecular changes during malignant progression, we selected an index patient to obtain parallel tissue samples from the primary and metastatic tumors. In the metastatic tissue, 10 unique molecular alterations, including those in
TP53
and
APAF1
, were detected. In vitro functional experiments showed that
APAF1
depletion increased the tumor potency of cells expressing NAB2-STAT6 fusion protein under treatment with staurosporine. We found that TP53 immunopositivity (
P
= 0.006) and loss of APAF1 immunoreactivity (
P
< 0.001) were significantly associated with malignant SFTs. Our study suggests that dysfunction of
TP53
and
APAF1
leads to impaired apoptotic function, and eventually contributes toward malignant SFT transformation.
Key messages
We firstly found that the
TERT
promoter mutation was strongly associated with malignant SFTs (
P
= 0.003) and the representative 1b (
NAB2
ex4-
STAT6
ex2) or 2a (
NAB2
ex6-
STAT6
ex16) fusion variants similarly contribute to tumorigenicity.
We also found that TP53 immunopositivity (
P
= 0.006) and loss of APAF1 immunoreactivity (
P
< 0.001) were significantly associated with malignant SFTs.
Our study suggests that dysfunction of
TP53
and
APAF1
leads to impaired apoptotic function, and eventually contributes toward malignant SFT transformation.
Sarcomas are challenging to study because of their rarity and histomorphological complexity. PD1 and PD-L1 inhibitors showed a promising anti-tumor effect in solid tumors, where a relationship ...between PD-L1 expression and the objective response has been evidenced.
In this study, we examined PD-L1 expression in 16 bone and soft tissue sarcoma cell lines of 11 different subtypes by means of western blot, flow cytometry and immunocytochemistry, and in 230 FFPE patient-derived tumor tissues by means of immunohistochemistry using three different antibody clones. The association between PD-L1 expression and clinicopathological features was evaluated.
We demonstrated that PD-L1 protein is highly expressed in pleomorphic rhabdomyosarcoma, fibrosarcoma, and dedifferentiated liposarcoma (DDLPS) cell lines. From the tissue microarray, undifferentiated pleomorphic sarcoma showed ≥ 1% immunoreactivity in 20%, 17.6%, and 16.3% of the cases with PD-L1 22C3, SP263, and SP142 antibodies, respectively. In whole sections stained with a PD-L1 22C3 antibody, DDLPS showed ≥ 1% immunoreactivity in 21.9% of the cases. In DDLPS group, cases with ≥ 1% PD-L1 expression showed statistically significantly worse recurrence-free survival (P = 0.027) and overall survival (P = 0.017) rates. Upon interferon-gamma treatment, the mRNA expression levels of PD-L1 were elevated in the HS-RMS-1, LIPO-224B, MLS1765, RH30, and RH41 cell lines.
We found that the expression of PD-L1 in sarcoma differs depending on the histologic subtype and the PD-L1 antibody clones. These results may serve as primary data for the selection of appropriate patients when applying PD1/PD-L1 inhibitor therapy in sarcoma.
Programmed cell death ligand 1 (PD-L1) expression is an important biomarker for predicting response to immunotherapy in clinical practice. Hence, identification and characterization of factors that ...predict high expression of PD-L1 in patients is critical. Various studies have reported the association of PD-L1 expression with driver genetic status in non-small cell cancer; however, the results have been conflicting and inconclusive. We analyzed the relationship between PD-L1 expression and clinicopathological factors including driver genetic alterations in 1000 resected lung cancers using a clinically validated PD-L1 immunohistochemical assay. PD-L1 expression was significantly higher in squamous cell carcinoma (SCC) compared to adenocarcinomas. PD-L1 expression in adenocarcinoma was associated with higher N-stage, solid histologic pattern,
wild type, and
positive, but no significant association with the clinicopathological factors in SCC.
mutant adenocarcinomas with distinctive clinicopathologic features, especially solid histologic pattern and higher stage showed higher PD-L1 expression. To the best of our knowledge, this study is the largest to evaluate the association between PD-L1 expression and clinicopathological and molecular features in lung cancer with a highly prevalent
mutation. Therefore, our results are useful to guide the selection of lung cancer, even
-mutated adenocarcinoma patients with PD-L1 expression, for further immunotherapy.
Purpose The purpose of this paper is to examine how a company’s symmetrical internal communication efforts could influence its employees’ perception of relationship outcomes with the company and the ...subsequent employee communication behaviors about the company to others and their turnover intention. Additionally, the mediation effects of employee-organization relationship (EOR) quality between symmetrical internal communication and employee engagement were tested. Design/methodology/approach The study collected the data from a survey of randomly selected 438 individuals who work as sales representatives of the case organization. Respondents were randomly selected through stratified sampling. For the overall statistical procedure, this study adopted the two-step structural equation modeling: on the basis of the final measurement model analysis from confirmatory factor analysis, the proposed structural model was tested using latent variables. Findings The findings of this research clearly demonstrate: employee/internal communication management is linked with employee engagement; employee engagement enhances supportive employee communication behaviors and reduces turnover intention. Also, the mediation results show strong mediation of EORs on the effects of symmetrical internal communication on employee engagement. Research limitations/implications Employees’ communication behaviors such as megaphoning and scouting have special strategic values to organizations. With information seeking, selecting, forwarding, and sharing behaviors of employees, organizations may obtain more valuable information than through formal procedures and channels. Professional literature has long been supporting the importance of fostering positive employee communication behaviors (ECBs), suggesting that WOM and information from the employees deemed as most trustworthy by the external publics. ECBs about their organizations may be viewed as a testament of the quality of EOR. This study results show that employee engagement plays a key role in creating positive ECBs. Practical implications Pragmatically, as noted in the findings, symmetrical communication is an important factor that leads to positive ECB. To facilitate employees’ favorable communication regarding an organization, therefore, the organization needs to practice a two-way, employee-centered symmetrical communication system in its everyday communication management. Communication managers are advised to nurture internal communication practices that listen to the employees and invite their participation in addition to providing complete and fair information to employees. Second, by showing the significant positive influence of EOR on employee engagement and ECB, the finding of the study suggests that strategic relationship management with internal publics affect overall management effectiveness. Hence, organizational managers need to adopt various relationship cultivation strategies in their communication with employees, which have been previously proposed by several studies. Originality/value The findings of the study demonstrated that the effects of employee relationship management and symmetrical internal communication indeed exist beyond ECBs to the actual managerial outcomes. The findings also suggest a three-stage model of employee communication management: employee/internal communication management antecedents; employee engagement; and supportive outcomes of effective employee communication programs, such as supportive/extra ECBs.
Endocrine therapy resistance in hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer (BC) is a significant clinical challenge that poses several unmet needs in the management of the ...disease. This study aimed to investigate the prognostic value of c-MET-positive circulating tumor cells (cMET+ CTCs), ESR1/PIK3CA mutations, and cell-free DNA (cfDNA) concentrations in patients with hormone receptor-positive (HR+) metastatic breast cancer (mBC).
Ninety-seven patients with HR+ mBC were prospectively enrolled during standard treatment at Samsung Medical Center. CTCs were isolated from blood using GenoCTC
and EpCAM or c-MET CTC isolation kits. PIK3CA and ESR1 hotspot mutations were analyzed using droplet digital PCR. CfDNA concentrations were calculated using internal control copies from the ESR1 mutation test. Immunocytochemistry was performed to compare c-MET overexpression between primary and metastatic sites.
The proportion of c-MET overexpression was significantly higher in metastatic sites than in primary sites (p = 0.00002). Survival analysis showed that c-MET+ CTC, cfDNA concentration, and ESR1 mutations were significantly associated with poor prognosis (p = 0.0026, 0.0021, and 0.0064, respectively) in HR+/HER2- mBC. By contrast, EpCAM-positive CTC (EpCAM+ CTC) and PIK3CA mutations were not associated with progression-free survival (PFS) in HR+/HER2- mBC. Multivariate analyses revealed that c-MET+ CTCs and cfDNA concentration were independent predictors of PFS in HR+/HER2- mBC.
Monitoring c-MET+ CTC, rather than assessing c-MET expression in the primary BC site, could provide valuable information for predicting disease progression, as c-MET expression can change during treatment. The c-MET+ CTC count and cfDNA concentration could provide complementary information on disease progression in HR+ /HER2- mBC, highlighting the importance of integrated liquid biopsy.
This study examined the effects of perceptions of organizational justice on the quality of relationships between employees and organizations, employee job engagement, and subsequent effects on ...employee turnover intention. Drawing from two complementary approaches (relationship management and human resources management perspectives), the current study proposed a model of employee turnover intention as the ultimate negative outcome of the relationship quality that employees perceive to have developed with their organization, which is predicted by perceptions of organizational justice. Additionally, the current study incorporated employee job engagement as the mediator connecting the EOR with the turnover intention. The results of an in-person survey of 438 salespeople for a South Korean company revealed that organizational justice perceptions had a significant and direct influence on the EOR quality. The findings further revealed that high perceptions of organizational justice by employees affected job engagement, which in turn negatively influenced turnover intention. Employee job engagement was also found to mediate the direct effects of justice perceptions and EOR on turnover intention.
Purpose
The purpose of this paper is to examine how a company’s symmetrical internal communication efforts could influence its employees’ perception of relationship outcomes with the company and the ...subsequent employee communication behaviors about the company to others and their turnover intention. Additionally, the mediation effects of employee-organization relationship (EOR) quality between symmetrical internal communication and employee engagement were tested.
Design/methodology/approach
The study collected the data from a survey of randomly selected 438 individuals who work as sales representatives of the case organization. Respondents were randomly selected through stratified sampling. For the overall statistical procedure, this study adopted the two-step structural equation modeling: on the basis of the final measurement model analysis from confirmatory factor analysis, the proposed structural model was tested using latent variables.
Findings
The findings of this research clearly demonstrate: employee/internal communication management is linked with employee engagement; employee engagement enhances supportive employee communication behaviors and reduces turnover intention. Also, the mediation results show strong mediation of EORs on the effects of symmetrical internal communication on employee engagement.
Research limitations/implications
Employees’ communication behaviors such as megaphoning and scouting have special strategic values to organizations. With information seeking, selecting, forwarding, and sharing behaviors of employees, organizations may obtain more valuable information than through formal procedures and channels. Professional literature has long been supporting the importance of fostering positive employee communication behaviors (ECBs), suggesting that WOM and information from the employees deemed as most trustworthy by the external publics. ECBs about their organizations may be viewed as a testament of the quality of EOR. This study results show that employee engagement plays a key role in creating positive ECBs.
Practical implications
Pragmatically, as noted in the findings, symmetrical communication is an important factor that leads to positive ECB. To facilitate employees’ favorable communication regarding an organization, therefore, the organization needs to practice a two-way, employee-centered symmetrical communication system in its everyday communication management. Communication managers are advised to nurture internal communication practices that listen to the employees and invite their participation in addition to providing complete and fair information to employees. Second, by showing the significant positive influence of EOR on employee engagement and ECB, the finding of the study suggests that strategic relationship management with internal publics affect overall management effectiveness. Hence, organizational managers need to adopt various relationship cultivation strategies in their communication with employees, which have been previously proposed by several studies.
Originality/value
The findings of the study demonstrated that the effects of employee relationship management and symmetrical internal communication indeed exist beyond ECBs to the actual managerial outcomes. The findings also suggest a three-stage model of employee communication management: employee/internal communication management antecedents; employee engagement; and supportive outcomes of effective employee communication programs, such as supportive/extra ECBs.
Most NTRK fusions occur at very low frequencies in various common cancers. Recent recommendations on NTRK testing recommend immunohistochemistry (IHC) as the initial test for tumor types with a low ...frequency of NTRK fusions. This study investigated the accuracy of an IHC assay to detect NTRK fusions and characterize the clinicopathological and molecular features of NTRK-rearranged tumors. This retrospective study was conducted on 1113 solid tumor samples known to harbor no oncogenic driver alterations, including 510 non-small cell lung cancers (NSCLC), 503 colorectal cancers (CRC), and 79 inflammatory myofibroblastic tumors (IMT). Additionally, 21 ALK expression-positive cases were included. TRK expression was evaluated using a pan-Trk IHC assay, and positive cases were validated using NGS. TRK expression was observed in three NSCLCs (0.6%), six CRCs (1.2%), and six IMTs (6%). NTRK fusions were finally detected in two NSCLCs (0.4%), six CRCs (1.2%), and one IMT (1%). In NSCLC and CRC, the majority of NTRK fusions were readily discernible due to diffuse moderate-to-strong cytoplasmic staining on pan-Trk IHC. In IMT, focal weak nuclear staining indicated the presence of NTRK fusion. Therefore, the utility of pan-Trk IHC should be assessed considering that the difference in performance depends on tumor type.
The study, using a survey of 508 university student publics, investigates (a) the impacts and mechanisms that a relationship has on a public's perceptions and behavior around an issue and (b) how ...relationship types impact a public's perception toward a tuition increase issue differently. The situational theory of publics was used as a theoretical framework. The results generally supported the theories. More important, the findings indicated that a communal relationship and an exchange relationship had different impacts on problem recognition, constraint recognition, and involvement recognition.
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