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Helicobacter pylori causes gastroduodenal disease, which is mediated in part by its outer membrane proteins (OMPs). To identify OMPs of H. pylori strain 26695, we performed a proteomic analysis. A sarcosine-insoluble outer membrane fraction was resolved by two-dimensional electrophoresis with immobilized pH gradient strips. Most of the protein spots, with molecular masses of 10 to 100 kDa, were visible on the gel in the alkaline pI regions (6.0 to 10.0). The proteome of the OMPs was analyzed by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. Of the 80 protein spots processed, 62 spots were identified; they represented 35 genes, including 16 kinds of OMP. Moreover, we identified 9 immunoreactive proteins by immunoblot analysis. This study contributes to the characterization of the H. pylori strain 26695 proteome and may help to further elucidate the biological function of H. pylori OMPs and the pathogenesis of H. pylori infection.

Introduction: There have been few studies about gene differences between patients with diffuse-type gastric cancer and those with intestinal-type gastric cancer. The aim of this study was to compare the transcriptomes of signet ring cell gastric cancer (worst prognosis in diffuse-type) and well-differentiated gastric cancer (best prognosis in intestinal-type); NUDC was identified, and its prognostic role was studied. Materials and Methods: We performed next-generation sequencing with 5 well-differentiated gastric cancers and 3 of signet ring cell gastric cancer surgical samples. We performed gene enrichment and functional annotation analysis using the Database for Annotation, Visualization and Integrated Discovery bioinformatics resources. Immunohistochemistry was used to validate NUDC expression. Results: Overall, 900 genes showed significantly higher expression, 644 genes showed lower expression in signet ring cell gastric cancer than in well-differentiated gastric cancers, and there was a large difference in adhesion, vascular development, and cell-to-cell junction components between the 2 subtypes. We performed variant analysis and found 52 variants and 30 cancer driver genes, including NUDC. We analyzed NUDC expression in gastric cancer tissue and its relationship with prognosis. Cox proportional hazard analysis identified T stage, N stage, and NUDC expression as independent risk factors for survival (P < 0.05). The overall survival of the NUDC-positive group was significantly higher (53.2 ± 0.92 months) than that of the NUDC-negative group (44.6 ± 3.7 months) (P = 0.001) in Kaplan-Meier survival analysis. Conclusion: We found 30 cancer driver gene candidates and found that the NUDC-positive group showed significantly better survival than the NUDC-negative group via variant analysis. [ABSTRACT FROM AUTHOR]

Peroxiredoxin IV (PRDX4) is a multifunctional protein that is involved in cell protection against oxidative injury, regulation of cell proliferation, modulation of intracellular signaling, and the pathogenesis of tumors. We previously conducted a proteomic analysis to investigate tumor-specific protein expression in gastric cancer. The aim of the present study was to investigate whether PRDX4 could be a marker of poor prognosis in patients with gastric cancer. Immunohistochemistry was used to validate PRDX4 as a prognostic marker for gastric cancer. Short hairpin RNA (shRNA)-mediated knockdown of PRDX4 expression in AGS cells and MKN28 cells was used for functional studies, and PRDX4 overexpression in PRDX4-depleted cells was used for knock-in studies. Based on immunohistochemistry data, TNM stage and PRDX4 were independent prognostic factors in the Cox proportional hazard model (P<0.05). In the survival analysis, the PRDX4-overexpressing group demonstrated significantly worse survival than the PRDX4-underexpression group (P<0.01). In vitro, knockdown of PRDX4 expression by shRNA caused a significant decrease in cancer invasion. Conversely, overexpression of PRDX4 in PRDX4-depleted cancer cells promoted migration and invasion. By measuring the expression of EMT-related genes, we found that E-cadherin was increased in shPRDX4 cells compared with control shMKN28 cells, and snail and slug were decreased in shPRDX4-1 cells compared with sh-control cells. Furthermore, the expression levels of these genes could be recovered in rescue experiments. In conclusion, the results of the present study suggested that PRDX4 is a marker of poor prognosis in gastric cancer and that PRDX4 is associated with cancer cell migration and invasion via EMT. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to investigate expression of gastric mucins in children and adolescents and to assess their relations with age and Helicobacter pylori ( H. pylori) infection. Methods Gastric biopsies were collected from 259 pediatric and adulthood patients with gastrointestinal symptoms among all of patients undergone gastroduodenoscopy from 1990 to 2004 at Gyeongsang National University hospital and assorted based on H. pylori infection, age, and intestinal metaplasia as follows; H. pylori infection before 5 years of age or not, H. pylori infection between 5 and 9 years of age or not, H. pylori infection between 10 and 14 years of age or not, H. pylori infection between 20 and 29 years of age or not and intestinal metaplasia between 21 and 35 years of age. Total 810 tissue slides from the subjects were examined regarding expressions of Mucin2 ( MUC2), Mucin5 AC ( MUC5 AC), and Mucin6 ( MUC6) in nine groups using immunohistochemical stains. A semiquantitative approach was used to score the staining extent of tissue slide. Results Increased expressions of MUC2, MUC5 AC, and MUC6 were noted in intestinal metaplasia compared with subjects infected with H. pylori between 20 and 29 years. Gastric expressions of MUC5 AC were decreased in older than 5 years with H. pylori compared with in older than 5 years without H. pylori ( p < .001). Expressions of MUC2 and MUC6 did not change significantly by H. pylori status. Some nuclear expressions of MUC2 and MUC6 were noted in children without intestinal metaplasia. Conclusions MUC5 AC might be affected by chronic H. pylori infection. In addition to biomarkers for intestinal metaplasia or prognostic factors for gastric cancer in adults, MUC2 and MUC6 in children might have an another role, based on ectopic gastric nuclear expressions of MUC2 and MUC6 in children without intestinal metaplasia. [ABSTRACT FROM AUTHOR]

The prognostic significance of O6-methylguanine DNA methyltransferase (MGMT) inactivation was evaluated in patients with diffuse large B-cell lymphoma (DLBCL) who received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in addition to rituximab. In this retrospective study, we used the methylation-specific polymerase chain reaction to investigate MGMT promoter methylation status and immunohistochemistry to evaluate MGMT expression in patients with DLBCL who received rituximab plus CHOP (R-CHOP) chemotherapy. No difference in patient characteristics, disease characteristics, response, or survival in patients with DLBCL who received front-line R-CHOP chemotherapy was observed according to MGMT methylation status and MGMT expression. On multivariate analysis, Grade 3–4 mucositis in the MGMT methylated group was significantly higher than that in the MGMT unmethylated group (hazard ratio (HR) 2.40, 95% CIs: 1.26–7.26, p = 0.014). This study demonstrated that inactivation of MGMT does not appear to play an important role in patients with DLBCL who received R-CHOP chemotherapy either with regard to the response rate or overall survival. Additionally, Grade 3–4 mucositis was found to be significantly related with inactivation of MGMT by a multivariate analysis. [ABSTRACT FROM AUTHOR]

Background. Helicobacter pylori has generally been observed only in the gastric mucous layer or in the spaces between gastric mucus-secreting cells and not in the gastric epithelial cells or in the lamina propria. The purpose of this study is to determine whether H. pylori invades the gastric mucosa, using an immunoelectron microscopical examination of human gastric mucosa infected with H. pylori. Materials and Methods. Five hundred gastric antral biopsy specimens were fixed in a periodate-lysin-paraformaldehyde solution, embedded in Lowicryl, sectioned, and examined with a light microscope. One hundred specimens moderately or severely infected with H. pylori were selected and were incubated with polyclonal rabbit anti–H. pylori antibody. The specimens were washed, incubated with 20 nm of colloidal gold–conjugated goat anti–rabbit IgG, stained with uranyl acetate and lead citrate, and observed with a transmission electron microscope. Results. In one case, a bacterium was observed within the cytoplasm of a gastric mucus-secreting cell; in another case, a few bacteria were observed within the cytoplasm of a stromal cell in the lamina propria. The bacteria could be differentiated from degenerated intracellular organelles by gold particles attached to the bacteria. Conclusion. H. pylori rarely invade the lamina propria and gastric cells. [ABSTRACT FROM AUTHOR]

Comments on a paper which reported that some monoclonal antibodies against Helicobacter pylori reacted with fetal gastric epithelial cells and the cells of various organs other than stomach. Factor which reduces the proliferation of peripheral blood mononuclear cells to purified protein derivative of tuberculin; Detection of CD68 antigen in some activated lymphocytes.

Background: Although many patients with functional dyspepsia experience headache concurrently with dyspeptic symptoms,studies suggesting mechanisms underlying this phenomenon are limited. Herein, we explore the relationshipbetween gastrointestinal inflammatory cells and presence of headache associated with dyspeptic symptoms in childrenwith Helicobacter pylori-negative functional dyspepsia. Methods: Fifty-six patients with H. pylori-negative functional dyspepsia underwent upper endoscopy with biopsy toinvestigate recurrent epigastric pain or discomfort. Patients were divided into two groups according to self-reportedpresence of headache associated with dyspeptic symptoms. Inflammatory cells including mast cells, and enteroendocrinecells in the gastroduodenal mucosa were evaluated. Associations between headache presence and cellular changes in thegastroduodenal mucosa were examined. Results: Headache was not associated with the grade of lymphocytes, neutrophil infiltration, or enteroendocrine celldensity in the gastroduedenal mucosa. However, headache was significantly associated with high mast cell density in thebody (27.81±8.71 vs. 20.30±8.16, p<0.01) and duodenum (23.16±10.40 vs. 14.84±5.88, p<0.01).Conclusions: Presence of headache associated with dyspeptic symptoms is strongly related to mucosal mast cell density inpediatric patients with H. pylori-negative functional dyspepsia. Thus, our results may help clinicians understand and treatheadache during dyspeptic symptoms in such pediatric patients. [ABSTRACT FROM AUTHOR]

Abstract: Activation of the NF-κB and mitogen activated protein (MAP) kinases plays an important role in the expression of inflammatory genes such as adhesion molecules. Although compound C is known as an AMPK inhibitor, AMPK-independent action of it has been recognized. Effects on the expression of ICAM-1 and VCAM-1 by compound C were investigated in TNF-α-activated human umbilical vein endothelial cells (HUVECs) in vitro and in thoracic aorta of rats treated with lipopolysaccharide (LPS) in vivo. Compound C inhibited ICAM-1 and VCAM-1 expression at the transcriptional as well as translational level in TNF-α-activated HUVECs. In both DN-AMPK- and AMPKα1-siRNA-transfected HUVECs, compound C still inhibited TNF-α-induced VCAM-1 and ICAM-1 expression, indicating that this is AMPK-independent action. Interestingly, compound C significantly inhibited NF-κB activity and translocation of p65 to nucleus in HUVECs when activated with TNF-α. Importantly, administration of compound C (0.2mg/kg) significantly reduced expression of both ICAM-1 and VCAM-1 in LPS-treated rat thoracic aortas. In addition, compound C significantly inhibited iNOS and production of NO in both TNF-α- and LPS-activated RAW 264.7 cells. Finally, compound C significantly inhibited phosphorylation of Akt and p-38MAPK but not protein kinase c or ERK1/2 in HUVECs. Taken together, we conclude that adhesion molecules (ICAM-1, VCAM-1) are to be the novel targets of compound C in preventing inflammatory insult to endothelial cells independent of AMPK inhibition via inhibition of NF-κB activity along with inhibition of phosphorylation of PI3K and P38 MAPK. [Copyright &y& Elsevier]

Purpose: Human peroxiredoxins (Prxs) are known as a family of thiol-specific antioxidant enzymes, among which Prx-I and –II play an important role in protecting cells from irradiation-induced cell death. It is not known whether Prx-IV also protects cells from ionizing radiation (IR). Methods and Materials: To evaluate the protective role of Prx-IV in IR, we transfected full-length Prx-IV cDNA into AMC-HN3 cells, which weakly express endogenous Prx-IV, and knocked down the expression of Prx-IV with siRNA methods using AMC-HN7 cells, which express high levels of endogenous Prx-IV. Radiosensitivity profiles in these cells were evaluated using clonogenic assay, FACS analysis, cell viability, and TUNEL assay. Results: Three Prx-IV expressing clones were isolated. Prx-IV regulated intracellular reactive oxygen species (ROS) levels and made cells more resistant to IR-induced apoptosis. Furthermore, the knockdown of Prx-IV with siRNA made cells more sensitive to IR-induced apoptosis. Conclusion: The results of these studies suggest that Prx-IV may play an important role in protecting cells from IR-induced apoptosis in head-and-neck squamous cell carcinoma. [Copyright &y& Elsevier]

We have analyzed a Helicobacter pylori plasmid, pHP489. The 1222-bp nucleotide sequence had one open reading frame, a DnaA-binding site, one direct repeat, and three inverted repeats. The (G + C) content of pHP489 was 33.3%. Although the nucleic acid sequence and deduced amino acid sequence were homologous to those of other bacterial plasmid Rep proteins, the degree of similarity was very low. A deletion analysis showed that the Rep protein was not required for the replication of pHP489 in its H. pylori host, but the host replication machinery was needed. [Copyright &y& Elsevier]

The nucleotide sequence of a 3955-bp Helicobacter pylori plasmid, pHP51 was determined, and two open reading frames, ORF1 and ORF2, were identified. The deduced amino acid sequence of ORF1 was highly conserved (87–89%) among plasmid replication initiation proteins, RepBs. The function of ORF2 was not assigned because it lacked known functional domains or sequence similarity with other known proteins, although it had a HPFXXGNG motif that was also found in the cAMP-induced filamentation (fic) gene. Three kinds of repeats were present on the plasmid outside of the ORFs, including the R1 and R2 repeats that are common in H. pylori plasmids. One 100-bp sequence detected in the noncoding region of pHP51 was highly similar to the genomic sequence of H. pylori 26695. [Copyright &y& Elsevier]

TNM stage still serves as the best prognostic marker in gastric cancer (GC). The next step is to find prognostic biomarkers that detect subgroups with different prognoses in the same TNM stage. In this study, the expression levels of epidermal growth factor receptor (EGFR) and cyclin D1 were assessed in 96 tissue samples, including non-tumorous tissue, adenoma, and carcinoma. Then, the prognostic impact of EGFR and cyclin D1 was retrospectively investigated in 316 patients who underwent R0 resection for GC. EGFR positivity increased as gastric tissue became malignant, and cyclin D1 positivity was increased in all the tumorous tissues. However, there was no survival difference caused by the EGFR positivity, while the cyclin D1-postive group had worse overall survival (OS) than the cyclin D1-negative group in stage I GC (10-year survival rate (10-YSR): 62.8% vs. 86.5%, p = 0.010). In subgroup analyses for the propensity score-matched (PSM) cohort, there were also significant differences in the OS according to the cyclin D1 positivity in stage I GC but not in stage II and III GC. Upon multivariate analysis, cyclin D1 positivity was an independent prognostic factor in stage I GC. In conclusion, cyclin D1 may be a useful biomarker for predicting prognosis in stage I GC.

Background: The enhancer of rudimentary homolog (ERH) protein is implicated in transcriptional regulation, cell cycle progression, and malignancy. We previously conducted a proteomics analysis using gastric cancer (GC) tissues and identified ERH as a biomarker candidate. The aim of this study was to investigate whether ERH may be useful as a prognostic marker for GC., Methods: Surgically resected GC tissue specimens were obtained from 327 patients who underwent gastrectomy at Gyeongsang National University Hospital. Immunohistochemistry (IHC) was used to validate ERH as a prognostic marker in these tissues. SNU601 and MKN74 cells with siRNA-mediated knockdown of ERH expression and ERH-overexpressing SNU601 and MKN74 knock-in cells were used for analysis of ERH function., Results: ERH was overexpressed in stomach cancer tissues compared with normal tissues according to proteomics analysis (n=29, P<0.01) of patient samples. Based on IHC, patients with tumors overexpressing ERH had lower T stage and lower TNM stage classifications, lower cancer recurrence rates and longer survival times than did patients with tumors showing low expression of ERH (P=0.04). In vitro , forced expression of ERH significantly decreased GC cell migration and invasion, and depletion of ERH triggered GC cell migration and invasion but had no effect on proliferation in vitro ., Conclusions: The findings from the present study show that ERH is associated with decreased cancer cell migration and invasion, suggesting that overexpression of ERH may serve as a marker of good prognosis for patients with GC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tcr-20-1498). The authors have no conflicts of interest to declare., (2020 Translational Cancer Research. All rights reserved.)

Background/aim: We aimed to evaluate the characteristics of gastric carcinoma with high excision repair cross complementing 1 (ERCC1) expression and the prognostic value of ERCC1 expression., Materials and Methods: ERCC1 expression was evaluated by immunohistochemistry in 309 surgically resected gastric carcinoma specimens using a tissue microarray. Cancer-related survival was analysed using competing risk analysis., Results: Compared to ERCC1-low gastric carcinomas, ERCC1-high gastric carcinomas showed less local invasion (p=0.0013), lower N stage (p=0.0302), earlier pTNM stage (p=0.0003), and less frequent recurrence (p=0002). Patients with ERCC1-high gastric carcinoma showed lower cumulative incidence function estimate of cancer-related death [3.37; 95% confidence intervaI (CI)=0.89-8.75] than did those with ERCC1-low gastric carcinoma (17.12; 95% CI=12.24-22.69; p-value by Gray's test=0.0012). Adjusted proportional sub-distribution hazard ratio for cancer-related death in the patients with ERCC1-high tumour was 0.272 (95% CI=0.084-0.878; p=0.0295)., Conclusion: High ERCC1 expression may be an independent positive prognostic marker for gastric carcinoma., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: We previously demonstrated that CD44v9 and Ki-67 played an important role in predicting poor prognosis of early gastric cancer (EGC). However, little is known about combined use of both biomarkers as prognostic biomarker. The present study was performed to investigate the significance of CD44v9 and Ki-67 expression as a combination biomarker for EGC., Materials and Methods: With tissue microarray for 158 EGC tissues, we performed immunohistochemical staining for CD44v9 and Ki-67. The whole patients were divided into three groups (group A, CD44v9- negative/Ki-67-low; group B, neither group A or C; and group C, CD44v9-positive/Ki-67- high). Its clinical significance was re-analyzed with adjustment via propensity score matching (PSM). For validation, we performed bootstrap resampling., Results: The median follow-up duration was 90.4 months (range, 3.7 to 120.4 months). In the comparison according to CD44v9/Ki-67 expression, the combined use of the two biomarker clearly separated the three groups by 5-year survival rates (5-YSR, 96.3%, 89.8%, and 76.8% in group A, B, and C, respectively; p=0.009). After PSM, 5-YSR were 97.7% and 76.8% in group A+B and group C, respectively (p=0.002). Multivariable analysis demonstrated that group C had independently poor prognosis (hazard ratio, 9.137; 95% confidence interval, 1.187 to 70.366; p=0.034) compared with group A. Bootstrap resampling internally validated this result (p=0.016)., Conclusion: This study suggests that both positive CD44v9 and high Ki-67 expression are associated with poor prognosis in EGC, and the combined use of these markers provides better prognostic stratification than the single use of them.

Snail is a key regulator of epithelial-mesenchymal transition (EMT), which is a major step in tumor metastasis. Although the induction of Snail transcription precedes EMT, posttranslational regulation, especially phosphorylation of Snail, is critical for determining Snail protein levels or stability, subcellular localization, and the ability to induce EMT. To date, several kinases are known that enhance the stability of Snail by preventing its ubiquitination; however, the molecular mechanism(s) underlying this are still unclear. Here, we identified p38 MAPK as a crucial posttranslational regulator that enhances the stability of Snail. p38 directly phosphorylated Snail at Ser107, and this effectively suppressed DYRK2-mediated Ser104 phosphorylation, which is critical for GSK3β-dependent Snail phosphorylation and βTrCP-mediated Snail ubiquitination and degradation. Importantly, functional studies and analysis of clinical samples established a crucial role for the p38-Snail axis in regulating ovarian cancer EMT and metastasis. These results indicate the potential therapeutic value of targeting the p38-Snail axis in ovarian cancer. SIGNIFICANCE: These findings identify p38 MAPK as a novel regulator of Snail protein stability and potential therapeutic target in ovarian cancer., (©2019 American Association for Cancer Research.)

Background/aim: Multiple primary malignant tumors are common in patients with renal cell carcinoma. However, reports on the factors that can identify patients with a risk for subsequent primary malignancies have been lacking. This study aimed to investigate whether myoferlin expression can be used as a potential marker to predict subsequent primary malignancies in patients with clear cell renal cell carcinoma (ccRCC)., Materials and Methods: We evaluated the relationship of subsequent primary malignancies with clinicopathological factors and myoferlin expression in 152 patients with ccRCC, and we analyzed the strength of the association with myoferlin expression., Results: The development of subsequent primary malignancies exhibited significant correlation with patient age (p=0.029), sex (p=0.015), T stage (p<0.001), and myoferlin expression (p=0.017). Furthermore, myoferlin hyperexpression was determined as an independent risk factor for developing a subsequent primary malignant tumor in patients with ccRCC (odds ratio(OR), 2.485, 95% Confidence Interval(CI)=1.052-5.870, p=0.038)., Conclusion: Myoferlin hyperexpression can be a useful marker for predicting the development of subsequent primary malignancies in patients with ccRCC., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: S100A8 and S100A9 have been gaining recognition for modulating tumor growthand metastasis. This study aimed at evaluating the clinical significance of S100A8 and S100A9 innon-small cell lung cancer (NSCLC)., Methods: We analyzed the relationship between S100A8and S100A9 expressions, clinicopathological characteristics, and prognostic significance in tumorcells and peritumoral inflammatory cells., Results: The positive staining of S100A8 in tumorcells was significantly increased in male (p < .001), smoker (p = .034), surgical method other thanlobectomy (p = .024), squamous cell carcinoma (SQCC) (p < .001) and higher TNM stage (p = .022)compared with female, non-smoker, lobectomy, adenocarcinoma (ADC), and lower stage. Theproportion of tumor cells stained for S100A8 was related to histologic type (p < .001) and patientsex (p = .027). The proportion of inflammatory cells stained for S100A8 was correlated with patientage (p = .022), whereas the proportion of inflammatory cells stained for S100A9 was correlatedwith patient sex (p < .001) and smoking history (p = .031). Moreover, positive staining in tumorcells, more than 50% of the tumor cells stained and less than 30% of the inflammatory cellsstained for S100A8 and S100A9 suggested a tendency towards increased survivability in SQCCbut towards decreased survivability in ADC., Conclusions: S100A8 and S100A9 expressions might be potential prognostic markers in patients with NSCLC.

Background: For endometrioid carcinoma patients, International Federation of Gynecologists and Obstetricians (FIGO) histologic grading is very important for identifying the appropriate treatment method. However, the interobserver discrepancy with this three-tiered grading system is a serious potential problem. In this study, we used immunohistochemistry to analyze the relationship between FIGO histologic grading score and myoferlin expression., Methods: We studied the endometrioid carcinoma tissues of 60 patients from Gyeongsang National University Hospital between January 2002 and December 2009. Immunohistochemical analysis of myoferlin was performed on tissue microarray blocks from surgical specimens., Results: Myoferlin expression was observed in 58 of 60 patients. Moderate and strong myoferlin expression was observed in low-grade endometrioid carcinoma, while there was a tendency toward loss of myoferlin expression in high-grade endometrioid carcinoma (p<.001)., Conclusions: Our study revealed that myoferlin loss is significantly correlated with high FIGO grade of endometrioid carcinoma.

Background: The immunotherapeutic role of programmed death-ligand 1 (PD-L1) in life expectancy in many cancers has been highlighted. However, data regarding PD-L1 expression in papillary thyroid carcinoma (PTC) are limited. In this study, we describe the PD-L1 and programmed cell death protein 1 (PD-1) expressions in PTC and analyze their correlation with lymph node (LN) metastasis., Methods: Clinicopathological data were obtained from 116 patients with PTC who were treated in Gyeongsang National University Hospital, Jinju, Korea in 2009. Tissue microarray blocks were made using representative paraffin blocks of classical PTCs excluding follicular variants. Two pathologists graded the proportion and intensity of PD-L1 and PD-1 expression in both tumor and inflammatory cells. According to their proportions, positive PTC cells were scored as negative (0%), grade 1 (1%-50%), and grade 2 (51%-100%). Similarly, positive inflammatory cells were graded as negative (0%), grade 1 (1%-10%), and grade 2 (11%-20%). The intensity of each protein expression was simplified as positive or negative., Results: A statistically significant correlation exists between the proportions of PD-1 and PD-L1 expression both in papillary carcinoma (p=.001) and peritumoral lymphoid cells in the thyroid (p<.001). In addition, the proportion of PD-L1 expression in PTC cells was closely related to metastatic LNs (p=.036)., Conclusions: PD-L1 is a valuable predictive marker for LN metastasis in PTC. Immunomodulating therapies that inhibit PD-L1 might be an option for patients with LN metastasis.