Clinicopathological Significance of Nucleosome Remodeling and Deacetylase Complex Expression in Endometrial Carcinoma.

BACKGROUND/AIM: Only a few studies have examined the expression of nucleosome remodeling and deacetylase complex in endometrial carcinoma (EC). The aim of this study was to analyze the expressions of histone deacetylase (HDAC1), HDAC2, and chromodomain helicase DNA-binding protein 4 (CHD4) in EC. PATIENTS AND METHODS: Sixty cases of EC were categorized into two clusters based on the expression levels of the three proteins. RESULTS: Cluster 1 (C1) exhibited elevated expressions of HDAC2 and CHD4 compared with cluster 2 (C2). Notably, 75% of cases in C2 represented non-aggressive histological types, whereas 37.5% of cases in C1 manifested aggressive types. C2 exclusively comprised pathological tumor stage 1 (pT1) tumors, whereas C1 included pT2 and pT3 tumors. In C1, 25% of cases displayed aberrant p53 expression, contrasting with the absence of such expression in C2. Furthermore, only one patient in C2 experienced disease recurrence, whereas 20.8% of patients in C1 developed recurrent tumors. CONCLUSION: High HDAC2 and CHD4 expression may be associated with adverse clinicopathological characteristics in EC. Further studies are needed to validate these results.

Next Generation Sequencing Analysis of Fibrin-associated Large B-cell Lymphoma Reveals Pathogenic Single Nucleotide Variants.

BACKGROUND/AIM: Fibrin-associated large B-cell lymphoma (FA-LBCL) is a newly identified subtype of Epstein-Barr virus (EBV)-associated lymphoma. Arising within fibrinous material in confined spaces, FA-LBCL is associated with chronic inflammation. We herein report histopathologic features and molecular alterations of three cases of FA-LBCL to refine this new disease entity. MATERIALS AND METHODS: We performed immunohistochemical staining for CD3, CD20, CD10, Bcl-2, Bcl-6, MUM-1, CD10, and c-Myc and in situ hybridization for EBV-encoded RNA. Additionally, targeted DNA sequencing was conducted using commercially available gene panels. RESULTS: Three cases of FA-LBCL developed underlying lesions of retroperitoneal cyst, cardiac myxoma, and pancreatic cyst. Histopathologic features of these lesions were characterized by aggregates of atypical large cells in a background of fibrinous cellular debris. Atypical lymphoid cells were positive for CD20, Bcl-2, MUM-1, and EBV-in situ hybridization, negative for CD10, and variably positive for Bcl-6 and c-Myc. NGS analysis revealed the presence of pathogenic mutations in BRIP1, SOCS1, and KRAS. CONCLUSION: This is the first report of NGS analysis in FA-LBCL cases. It provides precise clinicopathological and molecular traits and allows its recognition as a new entity.

Prediction of Oncotype DX Recurrence Score by Evaluating the Peritumoral Tumor Budding in Early-stage Breast Carcinoma.

BACKGROUND/AIM: The Oncotype DX Recurrence Score (ORS) predicts the likelihood of recurrence and the benefit of chemotherapy in patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative early-stage breast carcinoma (ESBC). Tumor budding (TB) is a poor prognostic factor in breast carcinoma. This study aimed to determine the clinicopathological significance of TB in predicting ORS in patients with ESBC. PATIENTS AND METHODS: We included 359 patients with ER-positive, HER2-negative ESBC. The number of peritumoral TB was assessed, and the cases were categorized into TB-low (<10 buds) and TB-high (≥10 buds) groups. RESULTS: Patients with TB-high ESBC (170/359; 47.4%) showed a significantly higher median ORS (15.0 vs. 13.0) than those with TB-low tumors (189/359; 52.6%). Multivariate analysis revealed that high TB level was an independent predictive factor for higher ORS in patients with ESBC. CONCLUSION: High TB in ESBC independently predicted higher ORS. TB may serve as a surrogate marker for predicting ORS in patients with ESBC.

Identification of Predictive Factors for Post-operative Recurrence and Clinical Outcomes of Primary Vulvar Extramammary Paget Disease.

BACKGROUND/AIM: Data regarding the clinicopathological factors predicting recurrence and prognosis in patients with vulvar extramammary Paget disease (VPD) are limited. Therefore, we aimed to identify predictive factors for recurrence and outcomes in patients with VPD. PATIENTS AND METHODS: Forty-five patients with VPD were included in this study. We reviewed electronic medical records and pathology slides to collect clinicopathological information. RESULTS: Eighteen cases (40.0%) had resection margin (RM) involvement. Twelve patients (26.7%) received adjuvant radiation therapy (RT). Ten patients (22.2%) experienced recurrence. The recurrence rate was higher in patients who underwent wide local excision or simple vulvectomy than in those who underwent radical vulvectomy. Positive RM involvement was a significant and independent predictive factor for worse recurrence-free survival (RFS). The overall survival rate of patients who received adjuvant RT was significantly higher than that of those who underwent surgery alone. CONCLUSION: A positive RM involvement independently predicted worse RFS. The recurrence rate was significantly associated with the type of surgical procedure performed. Additionally, adjuvant RT can improve the prognosis of patients with VPD.

Gastrointestinal Follicular Lymphoma: A Single-institutional Experience of 22 Cases With Emphasis on the Comprehensive Clinicopathological Analysis and Diagnostic Re-classification.

BACKGROUND/AIM: Distinguishing gastrointestinal involvement in classic follicular lymphoma (CFL) and duodenal-type follicular lymphoma (DFL) is crucial for proper treatment. This study aimed to describe an integrated diagnostic re-classification of gastrointestinal follicular lymphoma (GIFL) and identify useful features for its differential diagnosis. PATIENTS AND METHODS: We reviewed radiological and endoscopic images and pathology slides of 22 GIFL cases, not otherwise specified. RESULTS: Thirteen cases of duodenal grade 1 FL without nodal disease were re-classified as DFL. Five cases of non-duodenal grade 3 FL accompanied by nodal enlargement were re-classified as CFL. The DFL showed peripherally accentuated CD21 immunoreactivity, whereas the CFL showed strong homogeneous CD21 expression. Four atypical cases were re-classified as DFL and CFL in one and three cases, respectively. CONCLUSION: Our findings support the notion that DFL differs from CFL. In cases of GIFL with atypical features, the possibility of gastrointestinal involvement by CFL should be considered. CD21 expression patterns can assist in the differential diagnosis of CFL and DFL.

Clinicopathological Factors Influencing Resection Margin Involvement During Mohs Micrographic Surgery for Skin Tumors.

BACKGROUND/AIM: Mohs micrographic surgery (MMS) is a specialized procedure for removing skin tumors. Intraoperative assessment of the resection margin (RM) status using frozen section examination is a crucial component of MMS. This study aimed to identify significant clinicopathological characteristics that could help surgeons determine the optimal surgical extent. PATIENTS AND METHODS: One hundred and fifty-one patients with primary skin tumors were included. The relationship between RM involvement and the clinico-pathological characteristics was analyzed for each histological type. RESULTS: Basal cell carcinoma (BCC) was significantly more likely to exhibit positive RMs and required additional excision during MMS compared to squamous cell carcinoma. In addition, the probability of RM involvement was significantly higher in high-risk BCC subtypes. CONCLUSION: When planning MMS, considering the histological type and presence of high-risk morphology may help surgeons perform more effective procedures.

Clinicopathological Significance and Predictive Value of High Intratumoral Tumor Budding in Patients With Breast Carcinoma Treated With Neoadjuvant Chemotherapy.

BACKGROUND/AIM: The clinicopathological significance and predictive value of tumor budding (TB) in patients with breast carcinoma (BC) treated with neoadjuvant chemotherapy (NAC) have not been fully elucidated. This study aimed to evaluate the role of TB in predicting the response to NAC in patients with BC. PATIENTS AND METHODS: We reviewed the pre-NAC biopsy slides obtained from 81 patients with BC and assessed the number of intratumoral TB. The association between TB and response to NAC and clinicopathological characteristics was evaluated. RESULTS: High TB (≥10 per 20× objective field), which was associated with more frequent lymph node metastasis and lower pathological complete response (pCR) rate, was observed in 57 (70.2%) cases. Multivariate logistic regression analysis revealed that high TB independently predicted non-pCR. CONCLUSION: High TB is associated with adverse features of BC. High TB on pre-NAC biopsy can be used as a predictive biomarker for non-pCR in NAC-treated patients with BC.

High PPFIA1 expression promotes cancer survival by suppressing CD8+ T cells in breast cancer: drug discovery and machine learning approach.

BACKGROUND: PTPRF-interacting protein alpha 1 (PPFIA1) plays an important role as a regulator of cell motility and tumor cell invasion and is frequently amplified in breast cancer. The aim of this study was to investigate the clinicopathologic features, survival, anticancer immunities and specific gene sets related to high PPFIA1 expression in patients with breast cancer. We verified the importance of PPFIA1 and survival rates using machine learning and identified drugs that can effectively reduce breast cancer cells with high PPFIA1 expression. METHODS: This study analyzed clinicopathologic factors, survival rates, immune profiles and gene sets according to PPFIA1 expression in 3457 patients with breast cancer from the Kangbuk Samsung Medical Center cohort (456 cases), Molecular Taxonomy of Breast Cancer International Consortium (1904 cases) and The Cancer Genome Atlas (1097 cases). We applied gene set enrichment analysis (GSEA), in silico cytometry, pathway network analyses, in vitro drug screening, and gradient boosting machine (GBM) analysis. RESULTS: High PPFIA1 expression in breast cancer was associated with worse prognosis, with reduced tumor-infiltrating lymphocytes, especially CD8+ T cells, and increased PD-L1 expression. In pathway network analysis, PPFIA1 was linked directly to the tyrosine-protein phosphatase pathway and indirectly to immune pathways. The importance of PPFIA1's association with survival in GBM analysis was higher than that of perineural and lymphovascular invasion. In in vitro drug screening, expression of PPFIA1 on mRNA level positively correlated with sensitivity of cell lines to erlotinib. CONCLUSION: High PPFIA1 in patients with breast cancer is related to poor prognosis and decreased anticancer immune response, and erlotinib may be promising for development of therapeutic approaches in patients with tumors overexpressing PPFIA1.

Clinicopathological and Prognostic Significance of Programmed Death Ligand-1 SP142 Expression in 132 Patients With Triple-negative Breast Cancer.

BACKGROUND/AIM: The prognostic value of programmed death ligand-1 (PD-L1) expression in triple-negative breast cancer (TNBC) has not been sufficiently investigated. In this study, we examined whether PD-L1 expression status is associated with clinicopathological features and outcomes of patients with TNBC. PATIENTS AND METHODS: Immunostaining for PD-L1 SP142 was performed on tissue microarrays containing 132 TNBC samples. High PD-L1 expression was defined as ≥10% of the tumor area occupied by PD-L1-expressing cells. RESULTS: Thirty-five (26.5%) patients showed high PD-L1 SP142 expression on immune cells (ICs). High IC PD-L1 expression was significantly correlated with smaller tumor size (p=0.030), absence of lymphovascular invasion (p=0.024), and fewer lymph node metastases (p=0.002). Multivariate survival analysis revealed that high IC PD-L1 expression independently predicted better disease-free survival (DFS) of TNBC patients. CONCLUSION: High PD-L1 SP142 expression on ICs was significantly associated with favorable clinicopathological parameters and better outcomes in patients with TNBC. Our observations suggest that high IC PD-L1 expression can be used as an independent prognostic marker for predicting better DFS in patients with TNBC.

Clinicopathological Characterization of Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System.

BACKGROUND/AIM: Primary central nervous system diffuse large B-cell lymphoma (CNS DLBCL) is a rare entity, accounting for 3-4% of intracranial neoplasms. This study aimed to investigate the clinicopathological characteristics of primary CNS DLBCL patients and their prognostic implication. PATIENTS AND METHODS: We collected 74 cases of clinically and pathologically confirmed primary CNS DLBCL from two institutions. Disease-free survival (DFS) and overall survival (OS) were analyzed based on various clinicopathological parameters. RESULTS: Most cases (83.8%) were classified as activated B-cell immunophenotype by Hans algorithm and cell-of-origin classification did not influence the clinical outcome. On univariate analysis, age (>60 years) and ECOG performance status (≥2) were significantly associated with shorter DFS and OS, and MYC/BCL2 co-expression significantly impacted poor DFS. An anaplastic variant was diagnosed in only 2 cases, but it raised possible association with poor outcome. On multivariate analysis, ECOG performance status and age was associated with poor prognosis. CONCLUSION: In primary CNS DLBCL, age and performance status revealed the most significant association with prognosis. Cell-of-origin classification was not a significant prognostic factor in contrast to systemic DLBCL.

Assessing Resection Margin Status in Breast-conserving Surgery Specimens: Comparison Among Gross Evaluation, Frozen Section Analysis, and Permanent Section Diagnosis in 725 Patients With Breast Cancer.

BACKGROUND/AIM: An accurate evaluation of resection margin (RM) is critical in breast-conserving surgery (BCS) as negative RM status is critical for successful local control. We compared gross and microscopic methods for RM evaluation and analyzed their concordances. PATIENTS AND METHODS: Gross evaluation (GE), frozen section analysis (FSA), and permanent section diagnosis (PSD) were compared for specimens from 725 breast cancer patients. RESULTS: The RM was grossly involved in 74 cases (10.2%). The sensitivity and specificity of GE were 22.9% and 96.1%, respectively. FSA revealed positive RM in 290 cases (40.0%), with high sensitivity (86.7%) and specificity (83.1%). With PSD, 240 cases (33.1%) showed RM involvement. Discordant results between gross and microscopic methods were observed in 104 cases (14.3%). CONCLUSION: Our observations of the low sensitivity of GE, high discordance rate between gross and microscopic methods, and high sensitivity and specificity of FSA support the necessity of intraoperative FSA for assessing RM status during BCS.

High Receptor-interacting Serine/Threonine-protein Kinase 3 (RIP3) Expression Serves as an Independent Poor Prognostic Factor for Triple-negative Breast Carcinoma.

BACKGROUND/AIM: Receptor-interacting serine/threonine-protein kinase 3 (RIP3) is a key component related to tumor necrosis factor-dependent necroptosis. RIP3 has been known to be a predictive biomarker in many types of carcinomas. We aimed to investigate whether RIP3 expression is correlated with clinicopathological characteristics and the outcomes of patients with breast carcinoma. PATIENTS AND METHODS: We performed immunostaining for RIP3 and analyzed the association of RIP3 expression status with the clinicopathological characteristics and survival of 203 patients with invasive ductal carcinoma of the breast. RESULTS: High RIP3 expression was significantly correlated with lymph node metastasis and human epidermal growth factor receptor 2 positivity. In patients with triple-negative breast carcinoma (TNBC), high RIP3 expression was an independent prognostic factor for disease-free survival (DFS). RIP3-high TNBC showed the lowest DFS rate. CONCLUSION: High RIP3 expression is associated with aggressive clinical behavior of breast carcinoma. Our data suggest that RIP3 serves as an independent prognostic factor in TNBC.

ARL6IP5 reduces cisplatin-resistance by suppressing DNA repair and promoting apoptosis pathways in ovarian carcinoma.

Ovarian carcinoma (OC) is the most lethal gynecological malignancy due to frequent recurrence resulting from cisplatin-resistance. ARL6IP5 is a novel gene implicated to suppress cisplatin-resistance by activating apoptosis and inhibiting DNA repair through XRCC1 and PARP1. We investigated the clinicopathological and prognostic significance of the immunohistochemical ARL6IP5 expression on 79 post-chemotherapy OC patient tissue samples; in vitro, the effect of ARL6IP5 overexpression (OE) and knockdown (KD) on cancer hallmark functions and the effect of ARL6IP5 on the expression of DNA repair and apoptosis-related proteins were observed in OC cells and their cisplatin-resistant (CisR) counterparts. ARL6IP5 expression was significantly associated with chemotherapeutic response and was an independent prognosticator of progression-free and overall survival of high-grade serous OC patients. ARL6IP5-OE decreased cellular proliferation, invasion, migration, adhesion, and increased apoptosis (p < 0.05); the opposite was observed for ARL6IP5-KD. Notably, ARL6IP5-OE reduced cisplatin-resistance of both OC and CisR OC cells, while ARL6IP5-KD increased cisplatin-resistance (p < 0.05). ARL6IP5-OE suppressed the expressions of DNA repair proteins and increased those of pro-apoptotic proteins; the opposite was observed for ARL6IP5-KD. The recombinant ARL6IP5 protein (rARL6IP5) had the greatest apoptotic effect among cisplatin and olaparib, in both OC and CisR OC cells; moreover, rARL6IP5 was the only single agent in CisR OC cells to retain higher apoptotic efficacy compared with control (p < 0.05), indicating that the apoptotic pathway influenced by rARL6IP5 remained effective in CisR OC cells compared to cisplatin and olaparib. In conclusion, we demonstrated that ARL6IP5 is an independent prognosticator of OC patients with cellular functions of a tumor-suppressor, possibly influencing the development of cisplatin-resistance and progression of OC cells through regulation of DNA repair and apoptosis. rARL6IP5 had significantly greater apoptotic efficacy compared to conventional chemotherapeutic agents in both OC and CisR OC cells, suggesting that ARL6IP5 may be a valuable novel chemotherapeutic against CisR OC.

Combination of GATA3, SOX-10, and PAX8 in a Comprehensive Panel to Diagnose Breast Cancer Metastases.

BACKGROUND/AIM: It can be difficult to establish the origin of a tumor in metastatic breast cancer (MBC), especially with triple-negative breast cancer (TNBC) or high-grade features. We evaluated the diagnostic utility of GATA3, SOX10, and PAX8 panels in MBC by comparing their expression in each molecular subtype of MBC. PATIENTS AND METHODS: We evaluated 84 MBC and 37 primary TNBC cases using GATA3, SOX10, and PAX8 staining in whole tissue sections. RESULTS: GATA3 was least sensitive in the detection of metastatic TNBC (metastatic non-TNBC, 0.95; metastatic TNBC, 0.37). SOX10 had the lowest overall sensitivity (0.12) but was elevated in metastatic TNBC, even higher than GATA3 (0.59 vs. 0.37). The combination of GATA3, SOX10, and PAX8 expression showed the highest detection rate (MBC, 0.94; metastatic non-TNBC, 0.95; metastatic TNBC, 0.93). CONCLUSION: We recommend combining GATA3, SOX10, PAX8 expression profiling to confirm breast as the site of origin in metastatic MBC.

External Validation of ALK and ROS1 Fusions Detected Using an Oncomine Comprehensive Assay.

BACKGROUND/AIM: This study aimed to assess the yield of an Oncomine comprehensive assay v3 (OCAv3)-based next-generation sequencing (NGS) analysis for detecting anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) fusions in non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: NGS data from 85 NSCLC cases were reviewed. ALK and ROS1 fusion status was compared to conventional tests. RESULTS: ALK or ROS1 fusion reads were detected in 17 NSCLC cases. Results in 10 NSCLC cases showed concordance with conventional tests, high-count fusion reads, a lack of mutually exclusive mutations of ALK or ROS1, and frequent signet-ring cell component. Seven NSCLC cases showing discordant results exhibited low to intermediate fusion read counts and mutations mutually exclusive from ALK or ROS1. CONCLUSION: Cases showing high-count fusion reads in OCAv3-based NGS have a strong possibility of carrying ALK or ROS1 fusion. Cases with low- to intermediate-count fusion reads should be interpreted with caution and may require additional confirmative tests.

Proto-oncogene Pokemon in thyroid cancer: a potential promoter of tumorigenesis in papillary thyroid carcinoma.

BACKGROUND: Pokemon is an oncogenic transcription regulator that plays a critical role in cellular differentiation. Although it has been found to be overexpressed in several types of cancer involving different organs, its role in thyroid gland has yet to be reported. The objective of this study was to evaluate the expression of Pokemon in papillary thyroid carcinoma (PTC) based on clinicopathological parameters. METHODS: Tissue microarray samples derived from patients with PTC or benign thyroid disease were used to evaluate Pokemon expression based on immunohistochemical analysis. Correlations of its expression with various clinicopathological parameters were then analyzed. RESULTS: Pokemon expression was observed in 22.0% of thyroid follicular cells from the normal group, 44.0% from the group with benign thyroid diseases, and 92.1% from the group with PTC (p < .001). The intensity of Pokemon expression was markedly higher in the PTC group. Pokemon expression level and PTC tumor size showed an inverse correlation. T1a tumors showed strong expression levels of Pokemon. However, larger tumors showed weak expression (p = .006). CONCLUSIONS: Pokemon expression is associated with tumorigenesis of PTC, with expression showing an inverse correlation with PTC tumor size. This might be related to the negative regulation of aerobic glycolysis by Pokemon.

Low KIBRA Expression Is Associated with Poor Prognosis in Patients with Triple-Negative Breast Cancer.

Background and Objectives: Kidney and brain protein (KIBRA) is a protein encoded by the WW and C2 domain containing 1 (WWC1) gene and is involved in the Hippo signaling pathway. Recent studies have revealed the prognostic value of KIBRA expression; however, its role in breast cancer remains unclear. The aim of this study was to examine KIBRA expression in relation to the clinical and pathological characteristics of patients with breast cancer and to disease outcomes. Materials and Methods: We analyzed the expression of KIBRA and its correlation with event-free survival (EFS) outcomes in resected samples from 486 patients with breast cancer. Results: KIBRA expression was significantly different among the molecular subgroups (low KIBRA expression: luminal A, 46.7% versus 50.0%, p = 0.641; luminal B, 32.7% versus 71.7%, p < 0.001; human epidermal growth factor receptor 2 (HER2)-enriched, 64.9% versus 45.5%. p = 0.001; triple-negative, 73.6% versus 43.8%, p < 0.001). Low KIBRA expression was also associated with high nuclear grade (60.4% versus 37.8%, p < 0.001), high histologic grade (58.7% versus 37.0%, p < 0.001), and estrogen receptor (ER) negativity (54.2% versus 23.6%, p < 0.001). Low KIBRA expression was significantly associated with poor EFS (p = 0.041; hazard ratio (HR) 1.658; 95% confidence interval (CI), 1.015-2.709). Low KIBRA expression was an independent indicator of poor prognosis (p = 0.001; HR = 3.952; 95% CI = 1.542-10.133) in triple-negative breast cancer (TNBC). Conclusion: Low KIBRA expression was associated with higher histological grade, ER negativity and poor EFS of breast cancer. In particular, our data highlight KIBRA expression status as a potential prognostic marker for TNBC.

High BMI1 Expression with Low CD8+ and CD4+ T Cell Activity Could Promote Breast Cancer Cell Survival: A Machine Learning Approach.

BMI1 is known to play a key role in the regulation of stem cell self-renewal in both endogenous and cancer stem cells. High BMI1 expression has been associated with poor prognosis in a variety of human tumors. The aim of this study was to reveal the correlations of BMI1 with survival rates, genetic alterations, and immune activities, and to validate the results using machine learning. We investigated the survival rates according to BMI1 expression in 389 and 789 breast cancer patients from Kangbuk Samsung Medical Center (KBSMC) and The Cancer Genome Atlas, respectively. We performed gene set enrichment analysis (GSEA) with pathway-based network analysis, investigated the immune response, and performed in vitro drug screening assays. The survival prediction model was evaluated through a gradient boosting machine (GBM) approach incorporating BMI1. High BMI1 expression was correlated with poor survival in patients with breast cancer. In GSEA and in in silico flow cytometry, high BMI1 expression was associated with factors indicating a weak immune response, such as decreased CD8+ T cell and CD4+ T cell counts. In pathway-based network analysis, BMI1 was directly linked to transcriptional regulation and indirectly linked to inflammatory response pathways, etc. The GBM model incorporating BMI1 showed improved prognostic performance compared with the model without BMI1. We identified telomerase inhibitor IX, a drug with potent activity against breast cancer cell lines with high BMI1 expression. We suggest that high BMI1 expression could be a therapeutic target in breast cancer. These results could contribute to the design of future experimental research and drug development programs for breast cancer.

High-sensitivity C-reactive Protein and Regression of Low-grade Squamous Intraepithelial Lesion: The Role of Low-grade Inflammation in Cervical Carcinogenesis.

BACKGROUND: Inflammation is emerging as a potential mechanism of cervical carcinogenesis. However, few studies have investigated the association between host inflammatory status and the natural course of cervical precursor lesion. The aim of this study was to assess the probability of LSIL regression, associated with an inflammatory biomarker, high-sensitivity C-reactive protein (hs-CRP). METHODS: In a longitudinal cohort study, female participants were examined annually or biannually using cervical cytology between 2006 and 2015. Incident LSIL cases were included in the analysis, with regression defined as at least one consecutive normal cytologic result. A total of 520 women aged 22-64 years were followed up for LSIL regression. The multivariable-adjusted hazard ratios (HRs) for LSIL regression were estimated using a parametric proportional hazards model. RESULTS: During 827.5 person-years of follow-up, 486 out of 520 subjects (93.5%) showed LSIL regression. After adjusting several important potential confounders, a higher quartile of hs-CRP levels was significantly associated with a lower rate of regression (for quartile 4 vs quartile 1, inverse HR 1.33; 95% CI, 1.04-1.69; P for trend = 0.028). CONCLUSIONS: The low rate of spontaneous regression recorded in women with higher hs-CRP lends support to the role of the perturbated host inflammatory status in cervical carcinogenesis, and suggests that hs-CRP level could help monitor LSIL.

Atypical Mesonephric Hyperplasia of the Uterus Harbors Pathogenic Mutation of Kirsten Rat Sarcoma 2 Viral Oncogene Homolog (KRAS) and Gain of Chromosome 1q.

BACKGROUND/AIM: Mesonephric carcinoma (MNC) is a rare but notable entity of the female genital tract. While many researchers have acknowledged and studied MNC, much remains unknown on the characteristics of mesonephric remnant (MNR) or hyperplasia (MNH). There has not been any study examining the molecular features of MNR and MNH so far. The aim of this study was to investigate the clinicopathological and molecular characteristics of ten uterine mesonephric lesions, including two MNRs without atypia, four MNHs without atypia, and three MNHs with atypia. MATERIALS AND METHODS: We reviewed the electronic medical records and all available slides of ten cases from multiple institutions. Targeted sequencing and array comparative genomic hybridization were performed. RESULTS: Three atypical MNHs displayed nuclear enlargement, mild-to-moderate nuclear pleomorphism, and nuclear membrane irregularity, and harbored pathogenic Kirsten rat sarcoma 2 viral oncogene homolograt sarcoma 2 viral oncogene homolog (KRAS) mutation. Two of those that co-existed with MNC harbored the same sequence alterations as each of their adjacent MNC. One of the three atypical MNHs harbored chromosome 1q gain. CONCLUSION: Atypical MNH is a potential premalignant lesion in which KRAS mutation and chromosome 1q gain play an important role in the early stage of mesonephric carcinogenesis.