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.

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.

Clinicopathologic characteristics of early gastric cancer according to specific intragastric location.

BACKGROUND: Although the incidence of early gastric cancer (EGC) continues to rise, there have been few studies on the intra-gastric distribution and locational characteristics of EGCs. In addition, there has been no attempt to visualize the intra-gastric distribution of EGCs using a merged tumor map. METHODS: We investigated the anatomic distribution of 644 cases of EGCs and analyzed the correlation between clinicopathologic findings and location by dividing areas of the stomach vertically and transversely. Merged tumor maps were generated using 310 surgically resected cases. RESULTS: Early gastric cancer was most commonly located in the antrum (57.5%) along the lesser curvature (37.8%). The intra-gastric distributions were similar in the merged tumor maps. Vertically, cancers of the middle third were associated with younger patient age, larger tumor size, and more frequent poorly differentiated (PD) or signet ring cell histology than cancers in other sites. Submucosal invasion was most frequently observed in the upper third. When divided transversely, tumors in the anterior or posterior wall showed more frequent PD or signet ring cell histology than those along the lesser or greater curvatures. CONCLUSIONS: EGC is the most prevalent in the antrum along the lesser curvature and has characteristic locational features, including histologic type, invasion depth, patient age, and tumor size. These results will improve the endoscopic detection rate of EGC and help to determine endoscopic resectability.

The prognostic and predictive value of tumor-infiltrating lymphocytes and hematologic parameters in patients with breast cancer.

BACKGROUND: Carcinogenesis and tumor growth are associated with chronic inflammation and the host immune system. Here, we investigated the clinical significance and relationship between tumor-infiltrating lymphocytes (TILs) and hematologic parameters in patients with breast cancer. METHODS: Invasive ductal breast cancer patients (N = 145) who underwent surgery were retrospectively evaluated. Samples were obtained using a core needle biopsy for CD8+, FOXP3+ TIL assessment. Blood lymphocytes, neutrophils, monocytes, and platelets were obtained by peripheral venous punctures. RESULTS: CD8 + TILs were significantly associated with absolute lymphocyte count (ALC) and the absolute monocyte count (AMC). Low LMR (ALC/AMC) (cut-off - 5.3, range = 0.73-12.31) was associated with poor overall survival (OS) (p = 0.010), disease-free survival (DFS) (p = 0.005). However, in subgroup analysis, LMR did not have any value as a prognostic factor in HER2-positive breast cancers. TILs had different prognostic impacts across breast cancer subtypes, although they were not statistically significant. The treatment response after NAC tended to improve in breast cancer patients with high FOXP3+ TILs, low NLR (neutrophil count/ALC) (FOXP3 p for trend = 0.006, NLR p for trend = 0.063). CONCLUSIONS: A relevance between TILs and hematologic parameters in breast cancer was demonstrated. The influence of the immune system on breast cancer progression may differ by subtype.

Feasibility of Preoperative Axillary Lymph Node Marking with a Clip in Breast Cancer Patients Before Neoadjuvant Chemotherapy: A Preliminary Study.

BACKGROUND: The aim of this study was to determine the feasibility of image-guided marker-clip placement in axillary lymph nodes (ALNs) for breast cancer upon initial presentation and to assess the reliability of this method with sentinel lymph node biopsy (SLNB) for axillary restaging after neoadjuvant chemotherapy (NAC). METHODS: Between June 2015 and August 2016, a marker clip was placed at a clinically positive ALN under ultrasonography (US) guidance before initiation of NAC in 20 patients. Preoperative localization of marker-clipped LNs was performed, and the localized LNs were removed by SLNB. We compared the postoperative results of the marker-clipped LNs, SLNs and ALNs. RESULTS: Image-guided marker-clip placements and localization of marker-clipped LNs were performed successfully in 20 patients. A total of 24 marker clips were inserted, and 23 marker-clipped LNs were successfully retrieved during surgery (identification rate, 23/24, 95.8%). In the 11 patients with pathologically confirmed metastatic marker-clipped LNs, four became negative after NAC, and seven maintained metastatic residues on the marker-clipped LNs. Three of the seven patients had metastatic residues on the ALNs, and two of the three patients also had negative SLNs. Marker-clipped nodes accurately predicted the axillary nodal status in these two patients compared with SLNs alone. CONCLUSION: Image-guided marker-clip placement on positive ALNs before NAC and removal with SLNB is technically feasible. This technique can improve the accuracy of the residual disease evaluation on the axilla, especially in patients with negative SLNB results, and can identify candidates for limited axillary surgery after NAC.

Expression of epithelial-mesenchymal transition driver brachyury and status of tumor-infiltrating CD8+ and FOXP3+ lymphocytes in predicting treatment responses to neoadjuvant chemotherapy of breast cancer.

Brachyury has been characterized as a driver of epithelial-mesenchymal transition process which is regarded as an important mechanism of cancer cell invasion and metastatic progression. The status of tumor-infiltrating lymphocytes has been proposed to predict response to neoadjuvant chemotherapy in breast cancer. We investigated the clinical significance and value of tumor-infiltrating lymphocytes and brachyury as biomarkers to predict treatment responses to neoadjuvant chemotherapy in breast cancer. We also examined the correlation of the Neo-Bioscore with tumor-infiltrating lymphocytes and brachyury to indirectly predict long-term outcome. This retrospective study included a series of 44 consecutive patients treated between January 2011 and December 2015. All patient samples were obtained using core needle biopsy before neoadjuvant chemotherapy. The relationship of expression of Brachyury and tumor-infiltrating lymphocyte subsets (CD8+, forkhead box protein 3 tumor-infiltrating lymphocytes) with clinicopathological factors was assessed to identify its predictive role with respect to tumor response to neoadjuvant chemotherapy and the outcome. Of 44 patients, 6 showed no response, 31 had partial response, and 7 demonstrated pathological complete response. Forkhead box protein 3 was significantly higher in the response group than in the no response group (no response = 2.6, partial response = 7.0, complete response = 9.7, p = 0.020). Brachyury expression was inversely associated with response to neoadjuvant chemotherapy, but the difference was not statistically significant ( p = 0.62). We also observed a significant association between forkhead box protein 3 ( p = 0.001) and the Neo-Bioscore, while only a marginal difference was observed with CD8+ expression ( p = 0.074). This study demonstrated that forkhead box protein 3 expression has value as the only independent marker that predicts a good response to neoadjuvant chemotherapy and that it is related with a good prognosis according to the Neo-Bioscore. Brachyury was significantly associated with estrogen receptor positive and human epidermal growth factor receptor 2 negative status; further study would be needed to clarify how it affects treatment prognosis.

Expression Pattern of Smad4/GATA3 as a Predictor of Survival in Invasive Ductal Carcinoma of the Breast.

BACKGROUND: Smad4 and GATA3 proteins are known prognostic markers in various cancers. Smad4 is a mediator linked to both tumour suppression and progression. GATA3 is a regulator of development and morphogenesis of the mammary gland. We assessed and compared the predictive performance of Smad4 and GATA3 for clinical outcomes in patients with breast cancer. METHODS: The combined expression pattern based on Smad4+/- and GATA3+/- was evaluated by immunostaining using breast cancer tissue microarray, and the relationships between protein expression and clinicopathological variables were analysed. RESULTS: Smad4 expression was only associated with an ill-defined tumour border, whereas GATA3 was associated with several good prognostic factors. On analysis of combined markers, there was a significant difference in the expression of fascin (an important factor for cancer invasiveness) between the Smad4+/GATA3- and Smad4-/GATA3+ groups. Smad4+/GATA3- was correlated with worse clinicopathological parameters, relapse-free survival (RFS), and overall survival (OS), compared to Smad4-/GATA3+. CONCLUSION: Combined markers of Smad4/GATA3 showed a superior performance compared to single markers for predicting RFS and OS in patients with breast cancer.

Decreased expression of p27 is associated with malignant transformation and extrathyroidal extension in papillary thyroid carcinoma.

Cell cycle regulatory proteins including p16, p27, and p53 are well studied in various cancers. However, their single or concurrent roles related with the clinicopathological parameters are not clearly recognized. We analyzed the expression of p16, p27, and p53 cell cycle regulatory proteins in papillary thyroid carcinoma (PTC). To determine the prognostic significance of cell cycle regulatory proteins, 107 PTCs were examined. We analyzed the individual expression of p16, p27, and p53 and their concurrent expressions, with the relationship to various clinicopathological parameters including differentiation from benign lesions. High expression of p16 and p53 and low expression of p27 were related with the distinguishing of PTC from benign lesions. In addition, normal thyroidal tissue showed higher p27 expression than nodular hyperplasia. In relation to extrathyroidal extension (ETE), the low expression of p27 was related with the presence of ETE. The low expression of p27 and high expression of p16 and p53 may affect the development of PTC. In addition, low p27 expression is related with the existence of ETE.

High Ki67/BCL2 index is associated with worse outcome in early stage breast cancer.

AIMS: Breast cancers are heterogeneous, making it essential to recognise several biomarkers for cancer outcome predictions. Ki67 proliferation index and B cell lymphoma 2 (BCL2) proteins are widely used as prognostic indicators in many types of malignancies. While Ki67 is a marker of normal or tumour cell proliferation, BCL2 plays a central role in antiproliferative activities. A combination of these two biomarkers with contrary purposes can provide enhanced prognostic accuracy than an analysis using a single biomarker. METHODS: We evaluated Ki67 and BCL2 expression with 203 cases of breast cancer. The relative expression of each biomarker named as Ki67/BCL2 index was divided into two groups (low vs high) with the use of area under receiver operating characteristic curves. RESULTS: There were significant correlations between Ki67/BCL2 index and clinicopathological findings such as age, tumour stage, size and necrosis, histological grade, extensive intraductal component, lymphatic and vascular invasion, oestrogen receptor, progesterone receptor, human epithelial growth factor receptor 2 and p53 expression (all p<0.05). In univariate and multivariate analyses, high Ki67/BCL2 index correlated with shorter disease-free survival and overall survival in patients with early stage invasive ductal carcinoma (all p<0.05). CONCLUSIONS: The Ki67/BCL2 index should be considered as a prognostic predictor in patients with early stage invasive ductal carcinoma.

Aberrant DNA methylation of integrin α4 in human breast cancer.

Integrins are cell surface receptors that mediate cell-cell/extracellular interactions and have shown an association with metastasis or transformation in several cancers. However, the correlation between the clinicopathological status of breast cancer and the altered integrin α4 status is not clear. In this study, we investigated DNA methylation of integrin α4 in breast cancer. We retrieved 351 cases of surgically resected breast cancer (290 invasive carcinoma and 61 intraductal carcinoma). Methylation-specific polymerase chain reaction was performed to determine integrin α4 methylation status. Integrin α4 methylation was frequently observed in breast cancer specimens (145/351 cases, 41.3 %). In addition, DNA methylation of integrin α4 showed statistical correlation with HER2 positivity and higher histologic grade (p = 0.001, 0.008 in ductal carcinoma in situ and 0.003 in invasive ductal carcinoma). However, other clinicopathological data such as estrogen receptor, progesterone receptor, metastasis, and TNM status showed no statistical correlation. Moreover, we found that the downregulated expression of integrin α4 in a heavily methylated breast cancer cell line (ZR-75) was restored by treatment with 5-aza-2'deoxycytidine, a DNA methyltransferase inhibitor, implying transcriptional silencing by DNA methylation. We observed that integrin α4 methylation is associated with the histologic grade of tumors and lymph node metastasis. Also, this data supports a previous study that suggested integrin α4 and HER2 are involved in the same signaling pathway. DNA methylation of integrin α4 may be a poor prognostic factor which affects undifferentiated histologic change of breast cancer.

Age-related Differences in Spatially Resolved Transcriptomic Profiles of Patients With Hormone Receptor-positive Breast Carcinoma.

BACKGROUND/AIM: Patients' age may influence the response to chemotherapy and the clinical course of breast carcinoma. This study aimed to compare the spatial transcriptomic profiles between younger (≤50 years) and older (>50 years) patients with hormone receptor (HR)-positive breast carcinoma. PATIENTS AND METHODS: Seven cases of breast carcinoma were included. We performed digital spatial profiling and bioinformatic analysis to investigate the spatial transcriptomes of the epithelial and stromal compartments. RESULTS: In the epithelial compartment of three young-age breast carcinoma (YABC) cases, we found 21 up-regulated and 7 down-regulated genes. The top two most up-regulated genes were serpin peptidase inhibitor clade A member 1 and serine protease. The gene ontology enrichment analysis revealed a significant up-regulation of genes defining ribosomal structures and functions in YABCs. The gene set enrichment analysis revealed that gene sets defining early and late responses to estrogen, response to interferon-α, and tumor necrosis factor-α signaling were significantly enriched in YABCs. CONCLUSION: We described for the first time the age-related differences in spatially resolved transcriptomic profiles and up-regulated transcriptional pathways of HR-positive breast carcinoma. Our observations highlight the critical need for age-specific treatment strategies for breast carcinoma management.

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.

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.

Comparative Study on the Clinicopathologic and Molecular Characteristics of Primary and Secondary Diffuse Large B-cell Lymphoma in the Central Nervous System.

BACKGROUND/AIM: Diffuse large B-cell lymphoma of the central nervous system (CNS-DLBCL) is an aggressive B-cell lymphoma with clinical and molecular heterogeneity. Primary CNS-DLBCL (PCNSL) affects the brain, eyes, leptomeninges, or spinal cord without systemic involvement. Secondary CNS-DLBCL (SCNSL) manifests concurrently with systemic lymphoma or as an isolated CNS relapse with poor prognosis. MATERIALS AND METHODS: Next-generation sequencing (NGS) was used to identify genomic alterations in 32 PCNSL and 9 SCNSL cases. Single nucleotide variants and copy number variations in addition to the clinicopathologic data and proposed risk predictive values were compared to aid in diagnostic differentiation between the two types of lymphomas. RESULTS: The MCD genotype, characterized by mutations in MYD88 and CD79B, is the most common alteration in PCNSL and is associated with lower survival rates. The frequency of MYD88 mutation was significantly higher in PCNSL compared to SCNSL (75.0% vs. 33.3%; p=0.042). Recurrent copy number loss of 6p21 occurred in 56.1% of cases, more often in PCNSL (65.6%) than in SCNSL (22.2%) (p=0.028). Diagnostic positive predictive values (PPV) of MYD88 mutation and 6p21 loss for PCNSL were 89% and 91%, respectively. PPV of both alterations was 93% for the diagnosis of PCNSL. CONCLUSION: MYD88 mutation and 6p21 loss were significantly higher in PCNSL than in SCNSL, and novel risk prediction models based on these distinct genomic profiles can aid in the clinical differentiation of PCNSL and SCNSL.

Diagnostic and prognostic relevance of MMP-11 expression in the stromal fibroblast-like cells adjacent to invasive ductal carcinoma of the breast.

BACKGROUND: Matrix metalloproteinase 11 (MMP-11) is a matrix degrading enzyme known to be involved in the remodeling of extracellular matrix proteins. This enzyme recently has been reported to play a key role in tumor progression and results in poor clinical outcomes for several different types of tumors. METHODS: A total of 192 patients diagnosed with invasive ductal carcinoma between 2000 and 2005 were included in this study. MMP-11 expression in tumors and stromal fibroblast-like cells was analyzed by immunohistochemical staining on a tissue microarray. Subsequently, evaluation of the associations between MMP-11 expression and clinicopathological characteristics was performed. RESULTS: MMP-11 expression of stromal fibroblast-like cells was correlated with prognostic factors, including tumor size, metastasis, histological grade, central tumor fibrosis, p53 expression, and luminal A subtype and was linked to therapeutic markers, such as ER and HER2 (all p < 0.05). There was a significant relationship between worse overall survival and MMP-11 expression in both tumors and stromal fibroblast-like cells (all p < 0.05). In multivariate analysis, MMP-11 expression of stromal fibroblast-like cells was still significantly associated with poor prognosis (p = 0.043). CONCLUSIONS: MMP-11 expression was significantly related to clinicopathological parameters, which may be essential to the prediction of disease outcome in patients with invasive ductal carcinoma of the breast.

Expression of TWIST1, Snail, Slug, and NF-κB and methylation of the TWIST1 promoter in mammary phyllodes tumor.

TWIST1, Slug, Snail, SIP1, and NF-κB are overexpressed in various tumors and associated with metastasis and poor prognosis. In this study, we examined their potential roles in phyllodes tumor (PT). The expression of TWIST1, Snail, Slug, SIP1, and NF-κB in benign (n = 103), borderline (n = 38), and malignant (n = 38) PTs was examined by immunostaining. The methylation status of the TWIST1 promoter was analyzed by methylation-specific PCR. We detected high expression levels of TWIST1 in 47.4 % of borderline/malignant PTs and 31.1 % of benign PTs, Slug in 64 % of borderline/malignant PTs and 62.1 % of benign PTs, epithelial SIP1 in 75.0 % of borderline/malignant PTs and 86.3 % of benign PTs, stromal SIP1 in 35.5 % of borderline/malignant PTs and 22.3 % of benign PTs, and NF-κB in 63.2 % of borderline/malignant PTs and 52.4 % of benign PTs. Snail expression was detected in all cases. A high expression of TWIST1 (p = 0.026) and TWIST1 promoter methylation (p = 0.000) were significantly more frequent in borderline/malignant PTs than in benign PTs. Moreover, a high expression of at least four of the five antibodies was more commonly observed in borderline/malignant PTs than in benign PTs (p = 0.026). However, no relationship was found between the expression of TWIST1 or the other proteins examined and the clinical outcome. Our results suggest that a high expression of TWIST1 and related proteins plays a pivotal role in the malignant progression of PT.

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.

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.

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.