Expression of ROR1, pAkt, and pCREB in gastric adenocarcinoma.

The receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a transmembrane protein of receptor tyrosine kinase family. High expression of ROR1 is reported in many types of malignancies and is thought to be involved in tumor growth, apoptosis, and epithelial-mesenchymal transition. In this study, we examined the expression of ROR1, pAkt, and pCREB in gastric adenocarcinoma and analyzed with clinicopathologic factors and tumor proliferation. Tissue microarray blocks containing 424 gastric adenocarcinomas were used for immunohistochemical staining. Ki-67 labeling index was used for tumor proliferation activity. High expression of ROR1 (63%), pAkt (36%), and pCREB (20%) was observed in gastric adenocarcinomas, and expression of these proteins was well intercorrelated. ROR1 and pCREB expression was associated with Ki-67 labeling index (P < .001). Expression of pAkt and pCREB group showed longer survival in univariate analysis (P = .007 and P < .001, respectively). This is the first study that analyzed ROR1 expression in gastric adenocarcinoma tissue samples. We revealed that gastric adenocarcinomas highly express ROR1 and related proteins and its prognostic significance. ROR1 in gastric adenocarcinoma could be possible candidate of therapeutic target, and more comprehensive study is required.

MurSS: A Multi-Resolution Selective Segmentation Model for Breast Cancer.

Accurately segmenting cancer lesions is essential for effective personalized treatment and enhanced patient outcomes. We propose a multi-resolution selective segmentation (MurSS) model to accurately segment breast cancer lesions from hematoxylin and eosin (H&E) stained whole-slide images (WSIs). We used The Cancer Genome Atlas breast invasive carcinoma (BRCA) public dataset for training and validation. We used the Korea University Medical Center, Guro Hospital, BRCA dataset for the final test evaluation. MurSS utilizes both low- and high-resolution patches to leverage multi-resolution features using adaptive instance normalization. This enhances segmentation performance while employing a selective segmentation method to automatically reject ambiguous tissue regions, ensuring stable training. MurSS rejects 5% of WSI regions and achieves a pixel-level accuracy of 96.88% (95% confidence interval (CI): 95.97-97.62%) and mean Intersection over Union of 0.7283 (95% CI: 0.6865-0.7640). In our study, MurSS exhibits superior performance over other deep learning models, showcasing its ability to reject ambiguous areas identified by expert annotations while using multi-resolution inputs.

RCKD: Response-Based Cross-Task Knowledge Distillation for Pathological Image Analysis.

We propose a novel transfer learning framework for pathological image analysis, the Response-based Cross-task Knowledge Distillation (RCKD), which improves the performance of the model by pretraining it on a large unlabeled dataset guided by a high-performance teacher model. RCKD first pretrains a student model to predict the nuclei segmentation results of the teacher model for unlabeled pathological images, and then fine-tunes the pretrained model for the downstream tasks, such as organ cancer sub-type classification and cancer region segmentation, using relatively small target datasets. Unlike conventional knowledge distillation, RCKD does not require that the target tasks of the teacher and student models be the same. Moreover, unlike conventional transfer learning, RCKD can transfer knowledge between models with different architectures. In addition, we propose a lightweight architecture, the Convolutional neural network with Spatial Attention by Transformers (CSAT), for processing high-resolution pathological images with limited memory and computation. CSAT exhibited a top-1 accuracy of 78.6% on ImageNet with only 3M parameters and 1.08 G multiply-accumulate (MAC) operations. When pretrained by RCKD, CSAT exhibited average classification and segmentation accuracies of 94.2% and 0.673 mIoU on six pathological image datasets, which is 4% and 0.043 mIoU higher than EfficientNet-B0, and 7.4% and 0.006 mIoU higher than ConvNextV2-Atto pretrained on ImageNet, respectively.

Paraganglioma in the cauda equina. A case report.

Paraganglioma of the cauda equina is rare, and diagnosis is difficult. A 47-year-old woman presented with backache, with a 2-year history of pain radiating in her right lower extremity. Initial neurologic examination revealed mild hypaesthesia in the L4 dermatome on both sides. Spine MRI showed a well-delinated intradural extramedullary mass compressing the spinal cord. It extended from L2 to L4, with anterior compression of the spinal cord which was displaced posteriorly. Clinical and radiological findings suggested an ependymoma. Surgical decompression was performed from L2 to L4 through lumbar laminectomy under microscope. Intraoperatively, the patient experienced unexplained paroxysmal hypertension while manipulating the tumour, which was not relieved by hypotensive medication but resolved immediately after resection of the mass. Postoperatively, the neurologic status improved and the radiating pain was relieved. Histopathologic examination showed cellular perivascular arrangement which looked like 'pseudorosettes'. Taken together, these histologic and radiologic findings suggested a benign myxopapillary ependymoma. However, immunohistochemical examination showed reactivity with synaptophysin and chromogranin. Finally, histological examination of the specimen revealed a 'Zellballen' pattern of paraganglioma, and the final diagnosis of paraganglioma with secreting function was confirmed. Paraganglioma is a rare tumour that can exhibit a secreting function causing paroxysmal hypertension which may be life threatening. Therefore, the differential diagnosis is important. The diagnosis is based on close examination of the clinical, radiologic and pathologic findings.

Yet Another Automated Gleason Grading System (YAAGGS) by weakly supervised deep learning.

The Gleason score contributes significantly in predicting prostate cancer outcomes and selecting the appropriate treatment option, which is affected by well-known inter-observer variations. We present a novel deep learning-based automated Gleason grading system that does not require extensive region-level manual annotations by experts and/or complex algorithms for the automatic generation of region-level annotations. A total of 6664 and 936 prostate needle biopsy single-core slides (689 and 99 cases) from two institutions were used for system discovery and validation, respectively. Pathological diagnoses were converted into grade groups and used as the reference standard. The grade group prediction accuracy of the system was 77.5% (95% confidence interval (CI): 72.3-82.7%), the Cohen's kappa score (κ) was 0.650 (95% CI: 0.570-0.730), and the quadratic-weighted kappa score (κquad) was 0.897 (95% CI: 0.815-0.979). When trained on 621 cases from one institution and validated on 167 cases from the other institution, the system's accuracy reached 67.4% (95% CI: 63.2-71.6%), κ 0.553 (95% CI: 0.495-0.610), and the κquad 0.880 (95% CI: 0.822-0.938). In order to evaluate the impact of the proposed method, performance comparison with several baseline methods was also performed. While limited by case volume and a few more factors, the results of this study can contribute to the potential development of an artificial intelligence system to diagnose other cancers without extensive region-level annotations.

Automated Gleason Scoring and Tumor Quantification in Prostate Core Needle Biopsy Images Using Deep Neural Networks and Its Comparison with Pathologist-Based Assessment.

The Gleason grading system, currently the most powerful prognostic predictor of prostate cancer, is based solely on the tumor's histological architecture and has high inter-observer variability. We propose an automated Gleason scoring system based on deep neural networks for diagnosis of prostate core needle biopsy samples. To verify its efficacy, the system was trained using 1133 cases of prostate core needle biopsy samples and validated on 700 cases. Further, system-based diagnosis results were compared with reference standards derived from three certified pathologists. In addition, the system's ability to quantify cancer in terms of tumor length was also evaluated via comparison with pathologist-based measurements. The results showed a substantial diagnostic concordance between the system-grade group classification and the reference standard (0.907 quadratic-weighted Cohen's kappa coefficient). The system tumor length measurements were also notably closer to the reference standard (correlation coefficient, R = 0.97) than the original hospital diagnoses (R = 0.90). We expect this system to assist pathologists to reduce the probability of over- or under-diagnosis by providing pathologist-level second opinions on the Gleason score when diagnosing prostate biopsy, and to support research on prostate cancer treatment and prognosis by providing reproducible diagnosis based on the consistent standards.

Periodontal biotype modification using a volume-stable collagen matrix and autogenous subepithelial connective tissue graft for the treatment of gingival recession: a case series.

PURPOSE: The purpose of this study was to propose a technique for periodontal biotype modification through thickening of the entire facial aspect using a volume-stable collagen matrix and autogenous subepithelial connective tissue graft (CTG) for the treatment of gingival recession. METHODS: Four systemically healthy patients showing Miller class I or class II gingival recession in the mandibular incisor area were included in this study. Full-mouth scaling and root planing procedures were performed at least 4 weeks prior to periodontal plastic surgery. A split-thickness flap with a horizontal intrasulcular incision and 2 vertical incisions was used in cases 1-3, and the modified tunnel technique was used in case 4 for coronal advancement of the mucogingival complex. After the exposed root surfaces were debrided thoroughly, double-layered volume-stable collagen matrix was placed on the apical part of the recession and a subepithelial CTG harvested from the palatal area was placed on the coronal part. The amount of root coverage at 3 months postoperatively was evaluated in cases 1-3, and facio-lingual volumetric changes were analyzed in cases 1 and 2. RESULTS: Healing was uneventful in all 4 cases and complete root coverage was shown in cases 1-3. In case 4, reduction of gingival recession was observed at 3 months after surgery. In cases 1 and 2, a comparison of stereolithographic files from the preoperative and postoperative time points demonstrated that the entire facio-lingual volume had increased. CONCLUSIONS: The surgical technique suggested herein, using a volume-stable collagen matrix and autogenous subepithelial CTG, may be an effective method for periodontal biotype modification through thickening of the entire facial aspect for the treatment of gingival recession.

Programmed death-1 (PD-1) expression in cervical intraepithelial neoplasia and its relationship with recurrence after conization.

OBJECTIVE: Impaired local cellular immunity contributes to persistent human papillomavirus (HPV) infection and development of cervical intraepithelial neoplasia (CIN). Programmed death-1 (PD-1) and its ligands PD-ligand-1 (L1) and PD-L2 are negative regulators of T cell activity in various cancers, but few studies exist. The aim of this study was to determine the clinicopathologic and immunologic parameters (PD-1, PD-L1, and PD-L2) related to the persistence/recurrence of CIN after conization. METHODS: Medical records of 652 patients diagnosed with CIN and underwent conization were reviewed. The associations between clinicopathologic parameters (e.g., age, parity, initial HPV load, etc.) and persistence/recurrence of CIN were analyzed. Expression of PD-1, PD-L1, and PD-L2 was assessed on 100 conization specimens by immunohistochemistry (IHC) in women matched for propensity-score (50 with persistence/recurrence and 50 without). RESULTS: Initial HPV load (>1,000 relative light unit) and positive margin were shown to be significantly associated with CIN persistence/recurrence (p=0.012 and p<0.001, respectively). Multivariate analysis showed that margin status was an independent predictor of persistence/recurrence (hazard ratio=8.86; 95% confidence interval=1.67-16.81; p<0.001). On IHC analysis, none of the patients expressed PD-L1. PD-1+ T cells were observed in 25 of 100 patients. Also, PD-1+ T cells were significantly correlated with increasing grade of CIN (p=0.031). In addition, patients with persistence/recurrence had increased expression of PD-1 compared with those without (36% vs. 14%, respectively; p=0.020). Although PD-L2 expression did not differ between 2 groups, it was significantly higher in patients with high-grade CIN compared to low-grade (34.7% vs. 12%, respectively; p=0.041). CONCLUSION: Positive surgical margin and expression of PD-1+ T cells were associated with CIN persistence/recurrence after conization.

Clinical significance of pancreatic intraepithelial neoplasia in resectable pancreatic cancer on survivals.

PURPOSE: Noninvasive precursor lesions for pancreatic adenocarcinoma include pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm, and mucinous cystic neoplasm. PanIN is often found synchronously adjacent to resected pancreatic ductal adenocarcinoma (PDAC) tumors. However, its prognostic significance on outcome after PDAC resection is unknown. The purpose of the current study was to determine if the presence of PanIN has a prognostic or predictive effect on survival after resection for PDAC with curative intent. METHODS: We retrospectively reviewed the clinicopathologic data of patients who underwent pancreatectomy for PDAC from January 2002 to January 2013. Intraductal papillary mucinous lesions and mucinous cystic neoplasms were excluded. All available postoperative imaging and clinical follow-up data were reviewed. RESULTS: There were 95 patients who underwent pancreatectomy. Tumors were most commonly located in the pancreas head and as such pancreaticoduodenectomy was the most commonly performed operation. The median tumor size was 3.2 cm. An absence of PanIN lesions was identified in 39 patients (41%). Of the patients with PanIN lesions, high-grade PanIN (grade 3) was the most common type (64.3%) followed by grade 2 (28.6%). There was no significant difference in overall survival or disease-free survival between the non-PanIN and PanIN groups. CONCLUSION: The presence or absence of PanIN lesions did not affect survival in patients undergoing resection for pancreatic cancer. However, patients with high-grade PanINs tended to have better overall survival. Larger studies with longer follow up are needed to accurately determine its clinical significance.

Clear Cell Renal Cell Carcinoma with Intratumoral Granulomatous Reaction: A Case Report and Review of the Literature.

Granulomatous reaction associated with clear cell renal cell carcinoma (CCRCC) is a rare finding, and only a few cases have been described in the literature. It is postulated to occur due to cancer-related antigenic factors such as cancer cells themselves or soluble tumor antigens shed into the blood. Herein, we describe a case of a 56-year-old male patient diagnosed with CCRCC with intratumoral granulomatous inflammation.

Expression and prognostic significance of programmed death protein 1 and programmed death ligand-1, and cytotoxic T lymphocyte-associated molecule-4 in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignancies and causes of death worldwide. In this study, we assessed the correlation between clinicopathologic factors with programmed cell death protein 1 (PD-1) and programmed cell death ligand-1 (PD-L1), and cytotoxic T lymphocyte-associated molecule-4 (CTLA-4) expressions. Furthermore, we analyzed the prognostic significance of these proteins in a subgroup of patients. We retrospectively evaluated the PD-1, PD-L1, and CTLA-4 expressions in 294 HCC tissue microarray samples using immunohistochemistry. PD-1 and PD-L1 expressions were significant related to high CD8+ tumor-infiltrating lymphocytes (TILs) (r = 0.664, p < 0.001 and r = 0.149, p = 0.012). Only high Edmondson-Steiner grade was statistically related to high PD-1 expression. High PD-L1 expression was demonstrated as an independent poor prognostic factor for disease-free survival in addition to previous known factors, size >5 cm and serum albumin ≤3.5 g/dL in high CD8+ TILs group. We have demonstrated that the combined high expression of PD-L1 and CD8+ TIL is an important prognostic factor related to the immune checkpoint pathway in HCC and furthermore, there is a possibility that it could be used as a predictor of therapeutic response. Also, this result would be helpful in evaluating the applicable group of PD-1/PD-L1 blocking agent for HCC patients.

Overexpression of PD-L2 is associated with shorter relapse-free survival in patients with malignant salivary gland tumors.

OBJECTIVES: PD-1/PD-L1 and CTLA-4 have been investigated and are thought to play an important role in tumor evasion. This study aimed to investigate expression patterns of immune-related molecules, and their clinical impacts in malignant salivary gland tumors. PATIENTS AND METHODS: We performed immunohistochemical staining for PD-L1, PD-L2, CTLA-4, PD-1, and CD8+ tumor-infiltrating lymphocytes in 70 malignant salivary gland tumors. Protein expression was assessed by H-score by multiplying the staining intensity by the percentage of cells with positive staining. RESULTS: The tumors comprised mucoepidermoid carcinomas (38.6%), adenoid cystic carcinomas (21.4%), salivary duct carcinomas (15.7%), and others. In malignant salivary gland tumors, PD-L2 expression was high, while expression of PD-L1 was relatively low in terms of the percentage of positively stained cells and the staining intensity. In univariate analysis, PD-L2 expression (H-score <1 vs ≥1), PD-1 (H-score <1 vs ≥1), and CD8+ tumor-infiltrating lymphocytes (H-score <1 vs ≥1) were significant prognostic factors. In multivariate analysis, low PD-L2 expression (H-score <1) was independently associated with shorter relapse-free survival (hazard ratio =6.514; 95% confidence interval, 1.2-36.2; P=0.032). CONCLUSION: In summary, PD-L2 is potentially an important biomarker in malignant salivary gland tumors, especially in regard to relapse.

A randomized controlled clinical study of periodontal tissue regeneration using an extracellular matrix-based resorbable membrane in combination with a collagenated bovine bone graft in intrabony defects.

PURPOSE: The purpose of this study was to investigate the feasibility of regenerative therapy with a collagenated bone graft and resorbable membrane in intrabony defects, and to evaluate the effects of the novel extracellular matrix (ECM)-based membrane clinically and radiologically. METHODS: Periodontal tissue regeneration procedure was performed using an ECM-based resorbable membrane in combination with a collagenated bovine bone graft in intrabony defects around the teeth and implants. A novel extracellular matrix membrane (NEM) and a widely-used membrane (WEM) were randomly applied to the test group and the control group, respectively. Cone-beam computed tomography images were obtained on the day of surgery and 6 months after the procedure. Alginate impressions were taken and plaster models were made 1 week and 6 months postoperatively. RESULTS: The quantity of bone tissue, the dimensional changes of the surgically treated intrabony defects, and the changes in width and height below the grafted bone substitutes showed no significant difference between the test and control groups at the 6-month examination. CONCLUSIONS: The use of NEM for periodontal regeneration with a collagenated bovine bone graft showed similar clinical and radiologic results to those obtained using WEM.

Comparative, randomized, double-blind clinical study of alveolar ridge preservation using an extracellular matrix-based dental resorbable membrane in the extraction socket.

PURPOSE: The aim of this study was to radiographically and clinically compare the effect of extracellular matrix (ECM) membranes on dimensional alterations following a ridge preservation procedure. METHODS: One of 2 different ECM membranes was applied during a ridge preservation procedure. A widely used ECM membrane (WEM; Bio-Gide, Geistlich Biomaterials, Wolhusen, Switzerland) was applied in the treatment group and a newly developed ECM membrane (NEM; Lyso-Gide, Oscotec Inc., Seongnam, Korea) was applied in the control group. Cone-beam computed tomography (CBCT) scans and alginate impressions were obtained 1 week and 6 months after the ridge preservation procedure. Results were analyzed using the independent t-test and the nonparametric Mann-Whitney U test. RESULTS: There were no significant differences between the ECM membranes in the changes in the dimension, width, and height of the extraction socket or the quantity of bone tissue. CONCLUSIONS: The NEM showed comparable clinical and radiographic results to the WEM following the ridge preservation procedure.

A Case of Malignant PEComa of the Uterus Associated with Intramural Leiomyoma and Endometrial Carcinoma.

Perivascular epithelioid cell tumors (PEComas) refers to a family of mesenchymal neoplasms composed of angiomyolipomas, clear cell "sugar" tumors of the lung, and lymphangioleiomyomatoses. These tumors have a distinctive and common component of perivascular epithelioid cells that show an association with blood vessel walls and immunohistochemically display myomelanocytic differentiation. The unique neoplasms have been shown to have an expanded range through a variety of case reports, including visceral, intra-abdominal, soft tissue, and bone tumors. The retroperitoneum, abdominopelvic region, and uterus have been reported to be the most common sites. Most PEComas follow a benign course. However, reports of malignant PEComas are increasing. Many papers have described uterine PEComas, but to our knowledge, there have not yet been any reports of a malignant PEComa arising concomitant with another epithelial tumor and mesenchymal tumor. We report herein the case of a 67-year-old woman who experienced a malignant uterine PEComa infiltrating a preexisting intramural leiomyoma with synchronous well differentiated endometrial carcinoma and multiple liver and lung metastases.

Four-week histologic evaluation of grafted calvarial defects with adjunctive hyperbaric oxygen therapy in rats.

PURPOSE: The aim of this study was to characterize the healing in the grafted calvarial defects of rats after adjunctive hyperbaric oxygen therapy. METHODS: Twenty-eight male Sprague-Dawley rats (body weight, 250-300 g) were randomly divided into two treatment groups: with hyperbaric oxygen therapy (HBO; n=14) and without HBO (NHBO; n=14). Each group was further subdivided according to the bone substitute applied: biphasic calcium phosphate (BCP; n=7) and surface-modified BCP (mBCP; n=7). The mBCP comprised BCP coated with Escherichia-coli-derived recombinant human bone morphogenetic protein-2 (ErhBMP-2) and epigallocatechin-3-gallate (EGCG). Two symmetrical circular defects (6-mm diameter) were created in the right and left parietal bones of each animal. One defect was assigned as a control defect and received no bone substitute, while the other defect was filled with either BCP or mBCP. The animals were allowed to heal for 4 weeks, during which those in the HBO group underwent 5 sessions of HBO. At 4 weeks, the animals were sacrificed, and the defects were harvested for histologic and histomorphometric analysis. RESULTS: Well-maintained space was found in the grafted groups. Woven bone connected to and away from the defect margin was formed. More angiogenesis was found with HBO and EGCG/BMP-2 (P<0.05). None of the defects achieved complete defect closure. Increased new bone formation with HBO or EGCG/BMP-2 was evident in histologic evaluation, but it did not reach statistical significance in histometric analysis. A synergic effect between HBO and EGCG/BMP-2 was not found. CONCLUSIONS: Within the limitations of this study, the present findings indicate that adjunctive HBO and EGCG/BMP-2 could be beneficial for new bone formation in rat calvarial defects.

EGF induces epithelial-mesenchymal transition through phospho-Smad2/3-Snail signaling pathway in breast cancer cells.

Epithelial-mesenchymal transition (EMT) can contribute to tumor invasion, metastasis, and resistance to chemotherapy or hormone therapy. EMT may be induced by a variety of growth factors, such as epidermal growth factor (EGF). Most studies regarding EMT have focused on TGF-ß-Smads signaling. The mechanism of EGF-induced EMT via activation of the Smad2/3 in breast cancer cells, MCF-7 and MDA-MB-231, remains unclear. The expression levels of Snail, vimentin, and fibronectin were increased by EGF treatment in a time-dependent manner, while the expression level of E-cadherin was decreased. EGF-induced nuclear co-localization of phospho-Smad2/3 and Snail and cancer cell migration were inhibited by pretreatment with an ERK1/2 inhibitor, PD98059 and a phospho-Smad2 inhibitor, SB203580. Knockdown of Smad2/3 expression suppressed EGF-induced expressions of Snail, vimentin, fibronectin, and cancer cell invasion, suggesting an acquisition of the mesenchymal and migratory phenotype in less aggressive MCF-7 cells. Moreover, MDA-MB-231 cells were shown that EGF-induced EMT, and cell invasion through ERK1/2-phospho-Smad2/3-Snail signaling pathway. We have discovered that EGF-stimulated activation of Smad2/3 upregulated several key EMT markers, inhibited E-cadherin expression, promoted EMT, enhanced migration and invasion in MCF-7 and MDA-MB-231 breast cancer cells. Identification of this molecular mechanism may provide new molecular targets for the development of therapies for metastatic breast cancer.

Relief of Injection Pain During Delivery of Local Anesthesia by Computer-Controlled Anesthetic Delivery System for Periodontal Surgery: Randomized Clinical Controlled Trial.

BACKGROUND: Pain from local anesthetic injection makes patients anxious when visiting a dental clinic. This study aims to determine differences in pain according to types of local anesthetizing methods and to identify the possible contributing factors (e.g., dental anxiety, stress, and sex). METHODS: Thirty-one patients who underwent open-flap debridement in maxillary premolar and molar areas during treatment for chronic periodontitis were evaluated for this study. A randomized, split-mouth, single-masked clinical trial was implemented. The dental anxiety scale (DAS) and perceived stress scale (PSS) were administered before surgery. Two lidocaine ampules for each patient were used for local infiltration anesthesia (supraperiosteal injection). Injection pain was measured immediately after local infiltration anesthesia using the visual analog pain scale (VAS) questionnaire. Results from the questionnaire were used to assess degree of pain patients feel when a conventional local anesthetic technique (CNV) is used compared with a computer-controlled anesthetic delivery system (CNR). RESULTS: DAS and PSS did not correlate to injection pain. VAS scores were lower for CNR than for CNV regardless of the order in which anesthetic procedures were applied. VAS score did not differ significantly with sex. Pearson coefficient for correlation between VAS scores for the two procedures was 0.80, also indicating a strong correlation. CONCLUSION: Within the limitations of the present study, relief from injection pain is observed using CNR.

Detection of Human Papillomavirus in Korean Breast Cancer Patients by Real-Time Polymerase Chain Reaction and Meta-Analysis of Human Papillomavirus and Breast Cancer.

BACKGROUND: Human papillomavirus (HPV) is a well-established oncogenic virus of cervical, anogenital, and oropharyngeal cancer. Various subtypes of HPV have been detected in 0% to 60% of breast cancers. The roles of HPV in the carcinogenesis of breast cancer remain controversial. This study was performed to determine the prevalence of HPV-positive breast cancer in Korean patients and to evaluate the possibility of carcinogenic effect of HPV on breast. METHODS: Meta-analysis was performed in 22 case-control studies for HPV infection in breast cancer. A total of 123 breast cancers, nine intraductal papillomas and 13 nipple tissues of patients with proven cervical HPV infection were tested by real-time polymerase chain reaction to detect 28 subtypes of HPV. Breast cancers were composed of 106 formalin-fixed and paraffin embedded (FFPE) breast cancer samples and 17 touch imprint cytology samples of breast cancers. RESULTS: The overall odds ratio between breast cancer and HPV infection was 5.43 (95% confidence interval, 3.24 to 9.12) with I2 = 34.5% in meta-analysis of published studies with case-control setting and it was statistically significant. HPV was detected in 22 cases of breast cancers (17.9%) and two cases of intaductal papillomas (22.2%). However, these cases had weak positivity. CONCLUSIONS: These results failed to serve as significant evidence to support the relationship between HPV and breast cancer. Further study with larger epidemiologic population is merited to determine the relationship between HPV and breast cancer.

Programmed death-ligand 1 expression in gastric adenocarcinoma is a poor prognostic factor in a high CD8+ tumor infiltrating lymphocytes group.

Gastric adenocarcinoma is one of the most common causes of cancer-related death. In this study, we conducted immunohistochemical studies for PD-L1, PD-1, CTLA-4, and CD8 using tissue microarrays from 464 gastric cancer samples and evaluated the correlations between their expression, clinicopathologic factors, and five-year overall survival. PD-L1 and PD-1 expression was significantly correlated with several adverse prognostic pathologic factors, including higher T-stage, diffuse Lauren histologic type, and lymphatic invasion. Conversely, CTLA-4 expression was correlated with factors of favorable clinical outcomes. A complete case analysis revealed that high PD-L1 and PD-1 expression had an adverse effect on five-year overall survival in univariate analyses. Subgroup analyses wherein patients were divided into two groups according to CD8+ tumor infiltrating lymphocyte levels (high and low) showed that high PD-L1 expression was a significant adverse prognostic factor only in the high CD8+ tumor-infiltrating lymphocytes group. Further research and clinical trials are needed to determine the clinical usefulness of these findings.