The usefulness of evaluating PTEN expression for accurate grading of phyllodes tumors.

Phyllodes tumors (PTs) are classified as benign, borderline, or malignant based on histologic characteristics. However, because histological criteria are subjective and diagnosis requires integrating multiple findings, discrepancies often occur between observers. Therefore, it is necessary to discover biomarkers based on the molecular characteristics of PTs. This study aimed to identify dysregulated microRNAs (miRNAs) in PTs through miRNA profiling and determine whether expression of their target genes could be useful as PT biomarkers. MiRNA profiling was performed on 13 PTs (three malignant, three borderline, seven benign) and six fibroadenomas, and predicted target genes of dysregulated miRNAs were selected using three computation algorithms. The expression of two miRNAs, miR-155 and miR-200c, was 1.69-fold and 1.61-fold higher, respectively, in borderline and malignant PT groups than in the benign PT group (p < 0.05). KEGG pathway analysis revealed that the 374 target genes of these two miRNAs (miR-155 and miR200c) participated in several signaling pathways, adherens junction, cell cycle, and pathway in cancer. Immunohistochemical staining for PTEN, one of candidate target genes of miR-200c, was performed on whole slides of PT tissue classified as malignant (n = 9), borderline (n = 12), or benign (n = 21). Stromal tumor cells of high-grade PTs (borderline and malignant) had significantly lower PTEN expression than those of low-grade PTs (benign) (p-value ≤0.001). Semiquantitative analysis of PTEN expression, score 0-8, revealed that it correlated with histologic findings. Low PTEN expression (s-score of 6 or less) was used as a diagnostic criterion for high-grade PTs, it showed 100 % sensitivity and 95.2 % specificity in 42 cases of PTs. Currently, PT grading based solely on subjective histologic findings is challenging, but semiquantitative PTEN expression analysis could provide a more accurate and objective way to grade PTs.

Ultra violet-C pretreatment enhances the antimicrobial efficacy of unpeeled carrots against subsequent contamination with Listeria monocytogenes.

To our knowledge, this study is the first to elucidate the bactericidal efficacy of unpeeled carrots (hereafter referred to as carrots) pretreated with Ultra Violet-C (UV-C) against subsequent contamination with Listeria monocytogenes. Carrots pretreated with UV-C (240 mJ/cm2) exhibited a significant antilisterial effect within 2 h. In fact, the population of UV-C-pretreated carrots decreased from 7.94 log CFU/cm2 to levels below the limit of detection (LOD; <1.65 log CFU/cm2) within 24 h. For carrots that were not pretreated with UV-C, 3-4 log reductions were found after 24 h. Carrots pretreated with UV-C exhibited antimicrobial activity against another gram-positive pathogen, Staphylococcus aureus, but not against the gram-negative pathogens, E. coli O157:H7 and Salmonella enterica. Pretreatment with UV-C created a lasting antimicrobial effect as introducing L. monocytogenes on carrots, 72 h post-UV-C treatment, still maintained the antilisterial effect. Notably, all UV-C doses in the range of 48-240 mJ/cm2 induced a lasting antilisterial effect. The bactericidal effects against L. monocytogenes were confirmed in three varieties of washed and unwashed carrots (Danvers, Nantes, and Chantenay). Fluorescence microscopy confirmed the bactericidal effect of UV-C-pretreated carrots on the survival of L. monocytogenes. Conclusively, pretreating carrots with UV-C can reduce the population of L. monocytogenes to levels below the LOD and may further prevent pathogen growth during cold storage. Additional studies are necessary to discern the mechanism underlying the bactericidal efficacy of UV-C-pretreated carrots.

Value of glucose transport protein 1 expression in detecting lymph node metastasis in patients with colorectal cancer.

BACKGROUND: There are limited data on the use of glucose transport protein 1 (GLUT-1) expression as a biomarker for predicting lymph node metastasis in patients with colorectal cancer. GLUT-1 and GLUT-3, hexokinase (HK)-II, and hypoxia-induced factor (HIF)-1 expressions may be useful biomarkers for detecting primary tumors and lymph node metastasis when combined with fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT). AIM: To evaluate GLUT-1, GLUT-3, HK-II, and HIF-1 expressions as biomarkers for detecting primary tumors and lymph node metastasis with 18F-FDG-PET/CT. METHODS: This retrospective study included 169 patients with colorectal cancer who underwent colectomy and preoperative 18F-FDG-PET/CT at Chungbuk National University Hospital between January 2009 and May 2012. Two tissue cores from the central and peripheral areas of the tumors were obtained and were examined by a dedicated pathologist, and the expressions of GLUT-1, GLUT-3, HK-II, and HIF-1 were determined using immunohistochemical staining. We analyzed the correlations among their expressions, various clinicopathological factors, and the maximum standardized uptake value (SUVmax) of PET/CT. RESULTS: GLUT-1 was found at the center or periphery of the tumors in 109 (64.5%) of the 169 patients. GLUT-1 positivity was significantly correlated with the SUVmax of the primary tumor and lymph nodes, regardless of the biopsy site (tumor center, P < 0.001 and P = 0.012; tumor periphery, P = 0.030 and P = 0.010, respectively). GLUT-1 positivity and negativity were associated with higher and lower sensitivities of PET/CT, respectively, for the detection of lymph node metastasis, regardless of the biopsy site. GLUT3, HK-II, and HIF-1 expressions were not significantly correlated with the SUVmax of the primary tumor and lymph nodes. CONCLUSION: GLUT-1 expression was significantly correlated with the SUVmax of 18F-FDG-PET/CT for primary tumors and lymph nodes. Clinicians should consider GLUT-1 expression in preoperative endoscopic biopsy in interpreting PET/CT findings.

Comparative analysis of immunotherapy responses in small cell lung cancer patients with dermatomyositis.

Cancer-associated dermatomyositis (CAD), a paraneoplastic syndrome characterized by dermatomyositis (DM), frequently presents in association with small cell lung cancer (SCLC). Although the advent of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, their efficacy and safety in patients with concurrent autoimmune diseases (AD) and malignancies remains uncertain. Several studies have suggested the safe administration of ICIs in patients with AD, indicating that successful cancer therapy can alleviate CAD symptoms. Conversely, other studies have raised concerns about the potential for ICIs to exacerbate AD flares or immune-related adverse events (irAEs). A comparative analysis of two cases from our institution emphasizes the variability in ICI responses among SCLC patients with CAD. One patient, previously reported as a case study, exhibited significant clinical improvement in DM symptoms after ICI administration, whereas the other developed severe exfoliative skin changes and experienced an unfavorable prognosis. This variability emphasizes the need for careful patient selection and close monitoring during ICI treatment. We hypothesized that overweight or obese individuals and those with severe initial skin lesions and elevated lactate dehydrogenase levels are more susceptible to developing irAEs following ICI therapy. Therefore, caution is advised when considering immunotherapy in these patients.

Evaluation of efficacy of Silybum marianum flower extract on the mitigating hair loss in vitro and in vivo.

BACKGROUND: Natural components that can exert a wide range of anti-hair loss activity with fewer side effects are in high demand. The objective of this study was to investigate the anti-hair loss potential of Silybum marianum flower extract (SMFE) in vitro and in vivo. METHODS: The effect of SMFE on dermal papilla cells was evaluated by measuring cell proliferation and VEGF production in hair follicle dermal papilla cells (HFDPCs). In addition, to confirm the effect of SMFE on dermal papilla senescence, SA-ß-gal staining and senescence associated secretory phenotype (SASP) production such as IL-6 was observed in both replicative and hydrogen peroxide (H2 O2 )-induced senescence models. In a clinical study, hair growth was determined by reconstitution analysis after shaving the hair of the clinical subject's scalp and hair area. RESULTS: SMFE increased the proliferation and VEGF production of HFDPCs. It also suppressed cellular senescence of HFDPCs and IL-6 production in replicative senescence and oxidative stress-induced senescence models. The hair density and total hair count at 16 and 24 weeks after using hair shampoo containing SMFE were significantly increased compared with those of the placebo group. CONCLUSION: SMFE has the potential to be used as a natural ingredient for alleviating hair loss.

Particulate matter promotes cancer metastasis through increased HBEGF expression in macrophages.

Although many cohort studies have reported that long-term exposure to particulate matter (PM) can cause lung cancer, the molecular mechanisms underlying the PM-induced increase in cancer metastasis remain unclear. To determine whether PM contributes to cancer metastasis, cancer cells were cultured with conditioned medium from PM-treated THP1 cells, and the migration ability of the treated cancer cells was assessed. The key molecules involved were identified using RNA-seq analysis. In addition, metastatic ability was analyzed in vivo by injection of cancer cells into the tail vein and intratracheal injection of PM into the lungs of C57BL/6 mice. We found that PM enhances the expression of heparin-binding EGF-like growth factor (HBEGF) in macrophages, which induces epithelial-to-mesenchymal transition (EMT) in cancer cells, thereby increasing metastasis. Macrophage stimulation by PM results in activation and subsequent nuclear translocation of the aryl hydrocarbon receptor and upregulation of HBEGF. Secreted HBEGF activates EGFR on the cancer cell surface to induce EMT, resulting in increased migration and invasion in vitro and increased metastasis in vivo. Therefore, our study reveals a critical PM-macrophage-cancer cell signaling axis mediating EMT and metastasis and provides an effective therapeutic approach for PM-induced malignancy.

Immune checkpoint inhibitor therapy in a patient with small cell lung cancer and anti-transcriptional intermediary factor 1-γ antibody-positive dermatomyositis: A case report.

Autoimmune diseases (ADs) are closely related to cancers; 30% of dermatomyositis (DM) cases are associated with malignancy. In lung cancer patients accompanied by DM, the most frequent cancer type is small cell lung cancer (SCLC). Anti-transcriptional intermediary factor 1 γ (anti-TIF1γ) antibody is a promising marker for the assessment of cancer risk in DM patients. The recent use of immune checkpoint inhibitors (ICIs) for extensive-stage SCLC has improved patient outcomes. However, clinical trials of ICI excluded most patients with ADs because of the increased risk of toxicity. Nevertheless, recent evidences suggest that ICI may be appropriate for AD patients. A 76-year-old man diagnosed with extensive-stage SCLC and anti-TIF1γ Ab-positive DM developed limb weakness and typical skin manifestations of DM. Positron emission tomography-computed tomography showed diffuse uptake in all muscles. The results of a nerve conduction study and electromyography were consistent with acute myopathy. Electron microscopy showed tubuloreticular inclusions in endothelial cells. He was treated with corticosteroids for DM and chemotherapy with atezolizumab for SCLC. Despite concerns regarding the use of ICI because of DM, atezolizumab was administered under close observation. After treatment, tumor size decreased and his symptoms improved significantly. We believe that the response of SCLC to chemotherapy including ICI, had a positive effect on the improvement of DM. Clinicians should consider ICIs for SCLC patients with DM and carefully monitor the patient's symptoms during treatment.

Chronic demyelinating polyneuropathy preceding T-cell lymphoma: differentiation between primary neurolymphomatosis and paraneoplastic neuropathy.

A 49-year-old man presented with progressive asymmetric weakness and pain. Electrodiagnostic tests and nerve biopsy suggested chronic demyelinating polyneuropathy refractory to immune-modulating therapy. The patient's symptoms were aggravated, and he was finally diagnosed with T-cell lymphoma based on the findings of the second 18F-2 fluoro-2-deoxy-glucose positron emission tomography/CT performed 16 months after symptom onset. The patient received intravenous chemotherapy, but died 2 months later because of lymphoma progression. A clinical suspicion of neurolymphomatosis and early diagnosis are important for proper management.

Whole-exome sequencing reveals rare genetic variations in ovarian granulosa cell tumor.

Ovarian granulosa cell tumor (OGCT) is a rare ovarian tumor that accounts for about 2-5% of all ovarian tumors. Despite the low grade of ovarian tumors, high and late recurrences are common in OGCT patients. Even though this tumor usually occurs in adult women with high estrogen levels, the cause of OGCT is still unknown. To screen genetic variants associated with OGCT, we collected normal and matched-tumor formalin-fixed paraffin-embedded (FFPE) from 11 OGCT patients and performed whole-exome sequencing (WES) using Illumina NovaSeq 6000. A total of 1,067,219 single nucleotide polymorphisms (SNPs) and 162,155 insertions/deletions (indels) were identified from 11 pairs of samples. Of these, we identified 44 tumor-specific SNPs in 22 genes and four tumor-specific indels in one gene that were common to 11 patients. We used three cancer databases (TCGA, COSMIC, and ICGC) to investigate genes associated with ovarian cancers. Nine genes (SEC22B, FEZ2, ANKRD36B, GYPA, MUC3A, PRSS3, NUTM2A, OR8U1, and KRTAP10-6) associated with ovarian cancers were found in all three databases. In addition, we identified seven rare variants with MAF ≤ 0.05 in two genes (PRSS3 and MUC3A). Of seven rare variants, five variants in MUC3A are potentially pathogenic. Furthermore, we conducted gene enrichment analysis of tumor-specific 417 genes in SNPs and 106 genes in indels using cytoscape and metascape. In GO analysis, these genes were highly enriched in "selective autophagy", and "regulation of anoikis". Taken together, we suggest that MUC3A is implicated in OGCT development, and MUC3A could be used as a potential biomarker for OGCT diagnosis.

Ang II-Induced Hypertension Exacerbates the Pathogenesis of Tuberculosis.

It has been known that infection plays a role in the development of hypertension. However, the role of hypertension in the progression of infectious diseases remain unknown. Many countries with high rates of hypertension show geographical overlaps with those showing high incidence rates of tuberculosis (TB). To explore the role of hypertension in tuberculosis, we compared the effects of hypertension during mycobacterial infection, we infected both hypertensive Angiotensin II (Ang II) and control mice with Mycobacterium tuberculosis (Mtb) strain H37Ra by intratracheal injection. Ang II-induced hypertension promotes cell death through both apoptosis and necrosis in Mtb H37Ra infected mouse lungs. Interestingly, we found that lipid accumulation in pulmonary tissues was significantly increased in the hypertension group compared to the normal controls. Ang II-induced hypertension increases the formation of foamy macrophages during Mtb infection and it leads to cell death. Moreover, the hypertension group showed more severe granuloma formation and fibrotic lesions in comparison with the control group. Finally, we observed that the total number of mycobacteria was increased in the lungs in the hypertension group compared to the normal controls. Taken together, these results suggest that hypertension increases intracellular survival of Mtb through formation of foamy macrophages, resulting in severe pathogenesis of TB.

Primary Central Nervous System Involvement in Peripheral T-Cell Lymphoma: A Case Report.

Primary central nervous system T-cell lymphoma (PCNSTL) is an extremely rare type of brain tumor. There are only few reports on the imaging findings of patients with PCNSTL. Herein, we report the imaging findings of a patient with peripheral T-cell lymphoma-not otherwise specified that presented with numerous small nodular and patchy strongly enhancing lesions on MRI.

Molecular subtypes of triple-negative breast cancer: understanding of subtype categories and clinical implication.

BACKGROUND: Triple-negative breast cancer (TNBC) is a heterogeneous entity that encompasses several subtypes with distinct molecular characteristics. The patients with TNBCs show unpredictable response to the chemotherapy, and further there is the lack of effective agents. Thus, many studies have been underway to discover targeted therapy suitable for patients with specific genetic alterations in each molecular subtypes. TNBCs are classified as four major molecular subtypes according to the gene expression patterns. These are luminal androgen receptor (LAR), mesenchymal-like, immunomodulatory (IM), and basal-like types. CONCLUSION: Here, we discuss the unique molecular features of each subtype as well as promising targets for anti-cancer therapy.

Parathyroid hormone is associated with prostate cancer.

BACKGROUND: The present study investigated the association of serum parathyroid hormone (PTH), vitamin D, and calcium levels with prostate cancer (CaP). METHODS: The study population consisted of an experimental group [459 patients including 216 patients with CaP and 243 patients with benign prostate hyperplasia (BPH)] and a prostatectomy group (47 patients who underwent radical prostatectomy). Patients with serum creatinine levels >1.4 mg/dl, parathyroid disease, and/or PTH levels <10 pg/ml were excluded. Patients with CaP and patients with BPH were compared, and the correlation between serum parameters and clinical data was determined. Preoperative and postoperative PTH levels were compared in the prostatectomy group. RESULTS: Mean PTH levels were 41.67 ± 28.82 and 27.06 ± 17.32 pg/ml in the CaP and BPH groups, respectively (p < 0.001). When patients were divided into two groups as per prostate-specific antigen levels (≤20 or >20 ng/ml), Gleason score (≤7 or ≥8), and stage (≤T3 or ≥ T4), there was no significant difference in PTH levels between the two groups. Mean postoperative PTH levels (26.93 ± 13.58 pg/ml) were significantly lower than preoperative PTH levels (36.71 ± 21.04 pg/ml) in the same patients who underwent radical prostatectomy. CONCLUSION: Serum PTH levels were higher in patients with CaP than in patients with BPH and decreased significantly after radical prostatectomy. The present results suggest an association between serum PTH and CaP. Further large cohort studies are necessary to validate the present data.

Evaluation of Bone Remodeling After Simultaneous Sagittal Split Ramus Osteotomy and Mandibular Angle Ostectomy in Patients With Mandibular Prognathism.

PURPOSE: The present study assessed the postoperative bone remodeling after simultaneous sagittal split ramus osteotomy (SSRO) and mandibular angle ostectomy using a 3-dimensional analysis of computed tomography (CT) data. MATERIALS AND METHODS: We designed and implemented a retrospective study that included patients who had undergone SSRO with (study group) or without (control group) mandibular angle ostectomy. Using CT data taken immediately after (T1) and 6 months (T2) after surgery, the vertical and horizontal morphologic changes of the mandibular angle were evaluated and compared between the 2 groups. In the study group, the volumetric changes of the mandibular angle were assessed, and the bone regeneration rate was calculated. RESULTS: A total of 58 mandibular angles were evaluated (32 in the study group and 26 in the control group). The study group exhibited significantly greater vertical bone regrowth at the middle and posterior regions of the mandibular angle ostectomy line compared with that in the control group (middle, P < .001; posterior, P < .001). Both groups showed significant horizontal bone regrowth at 6 months postoperatively (P < .01). In the study group, the postoperative vertical bone regrowth was significantly associated with the extent of exposed bone below the angle ostectomy line at T1 for all regions (P < .001). The percentage of postoperative regenerated bone volume relative to the volume of bone removed intraoperatively was 41.8%. CONCLUSIONS: The present findings suggest that significant bone regrowth could occur after mandibular angle ostectomy with simultaneous SSRO. Therefore, it is necessary to consider bone remodeling patterns in the treatment planning stage for better and more predictable surgical outcomes.

Bacterial type III effector protein HopQ inhibits melanoma motility through autophagic degradation of vimentin.

Malignant melanoma is a fatal disease that rapidly spreads to the whole body. Treatments have limited efficiency owing to drug resistance and various side effects. Pseudomonas syringae pv. tomato (Pto) is a model bacterial pathogen capable of systemic infection in plants. Pto injects the effector protein HopQ into the plant cytosol via a type III secretion machinery and suppresses the host immunity. Intriguingly, host plant proteins regulated by HopQ are conserved even in humans and conferred in tumor metastasis. Nevertheless, the potential for HopQ to regulate human cancer metastasis was unknown. In this study, we addressed the suitability of HopQ as a possible drug against melanoma metastasis. In melanoma cells, overexpressed HopQ is phosphorylated and bound to 14-3-3 through its N-terminal domain, resulting in stronger interaction between HopQ and vimentin. The binding of HopQ to vimentin allowed for degradation of vimentin via p62-dependent selective autophagy. Attenuation of vimentin expression by HopQ inhibited melanoma motility and in vivo metastasis. These findings demonstrated that HopQ directly degraded vimentin in melanoma cells and could be applied to an inhibitor of melanoma metastasis.

Diagnostic significance of dual immunocytochemical staining of p53/cytokeratin20 on liquid-based urine cytology to detect urothelial carcinoma.

BACKGROUND: Urine cytology is a noninvasive and inexpensive method; however, it is limited in low sensitivity for detecting and monitoring urothelial carcinoma (UC). To overcome limitation of cytology, several tests using urine samples have been attempted that immunocytochemical staining is an inexpensive and easy to perform ancillary technique. Dual immunocytochemical staining for p53 and cytokeratin 20 (CK20) is assessed in liquid-based urine cytology slides. MATERIALS AND METHODS: Liquid-based urine cytology samples collected between 2008 and 2013 and matched follow-up biopsy samples of high-grade UC (HGUC) (n = 44) and low-grade UC (LGUC) (n = 14) were analyzed. RESULTS: Urine cytology showing atypical cells was subjected to dual-color immunostaining for p53 and CK20. The sensitivity of urine cytology combined with p53 and CK20 immunostaining was 77.3% in HGUC and 52.9% in LGUC. Of 20 cases diagnosed with atypia by urine cytology, 13 (65%) were positive for p53 or CK20. Dual immunocytochemical staining for p53/CK20 improved the diagnostic accuracy of urine cytology. CONCLUSIONS: The present results indicate that cytomorphology combined with p53/CK20 immunostaining is useful for the detection of HGUC and LGUC.

Basal-like Breast Cancer: Comparison of Imaging Characteristics.

BACKGROUND: Basal-like carcinoma is one of the breast subtypes that lacks expression of the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). It has a poor prognosis and aggressive behavior. It is in a heterogeneous group with various other types of cancer, including metaplastic carcinoma, carcinomas with medullary features, medullary carcinoma, adenoid cystic carcinoma, secretory carcinoma, and invasive carcinoma arising in the setting of BRCA1 mutations. Imaging features of basal-like cancers have not been uniform, and there are no studies with imaging comparisons between basal-like carcinomas. OBJECTIVES: To compare imaging features of basal-like carcinomas and to understand their characteristics. METHODS: By using our radiologic database, we retrospectively searched 37 cases of metaplastic carcinoma and 44 cases of invasive carcinoma with medullary features (ICMF). Two radiologists reviewed images according to ACR BI-RADS lexicon. RESULTS: The higher Ki-67 and absence of calcifications were statistically significant in ICMF than in metaplastic carcinoma. Metaplastic carcinoma demonstrated oval shape and parallel orientation more frequently. ICMF showed more irregular shape and angular margin on ultrasound, irregular or spiculated margin on breast MRI. ICMF showed more delayed washout pattern of enhancement than metaplastic carcinoma. Intratumoral T2, a very high signal was noted more in metaplastic carcinoma. CONCLUSION: Our study presents variable imaging features observed between basal-like carcinomas. Although it is not sufficient to predict clinical progress, aggressiveness or prognosis of basal-like carcinomas, the results of this study will be helpful in understanding and diagnosing various basallike carcinomas.

Genomic Landscape of Young-Onset Bladder Cancer and Its Prognostic Implications on Adult Bladder Cancer.

Due to the rare occurrence of young-onset bladder cancer (YBC), its genomic characteristics remain largely unknown. Twenty-nine biopsy-proven YBC cases were collected using a nation-wide search for bladder cancer diagnosed at 20 years or younger. Whole exome sequencing and RNA sequencing were carried out in 21 and 11 cases, respectively, and compared with those of adult bladder cancer (ABC) cases obtained from public databases. Almost all YBCs were low grade, non-invasive papillary tumors. YBC had a low mutation burden and less complex copy number alterations. All cases harbored putative driver mutations. Mutations were most commonly found in HRAS (10 cases), with a preference for exon 5. FGFR3 gene fusions were noted with various partner genes (7 cases). The alterations on HRAS and FGFR3 occurred in a mutually exclusive manner. Others included KRAS mutations (2 cases), chromosomes 4p and 10q arm-level deletions (1 case), and ERCC2 mutation (1 case). There were no point mutations in TP53 and FGFR3. The gene expression profiles of YBC were similar to those of the ABC group with good prognosis. None of the YBCs and ABCs with YBC-like mutations showed progression to muscle-invasive tumors. Our results suggest that bladder cancer with YBC-like mutations represents an indolent bladder tumor, regardless of age.

Complement Component C4d Deposition in the Placenta of Preeclampsia Patients and Renal Glomeruli in 1 Postpartum Renal Biopsy.

BACKGROUND: The classic disorder of placental malperfusion is preeclampsia (PE), in which the kidney is also a target organ, leading to renal dysfunction. Although the precise pathogenesis of PE is unknown, increasing evidence suggests that PE is associated with complement dysregulation. The maternal immune response to an allogenic fetus and excessive activation of the complement system may both be involved in the pathogenesis of PE. C4d deposition is considered to be evidence of antibody-mediated rejection in an allograft. This study investigated a correlation between C4d expression in the placenta and clinicopathologic features of PE patients. MATERIALS AND METHODS: Immunohistochemical staining for C4d was performed on placental tissue of PE patients (n=70) and normal pregnancy patients (n=30). Clinicopathologic features, such as maternal age and parity, placental weight, proteinuria, and histologic features of the placenta were evaluated. One PE patient who suffered from proteinuria after delivery received a renal biopsy. RESULTS: C4d expression was demonstrated in syncytiotrophoblast of chorionic villi. The expression of C4d was significantly more frequent in the placenta with PE (50%) than in the placenta lacking complications (14.3%) (P=0.001). C4d expression was significantly accompanied by increased syncytial knots in PE (P=0.045). Among PE patients, C4d expression was significantly correlated with low placental weight (P=0.001) and high proteinuria (P=0.018, Mann-Whitney U test). Renal biopsy of a PE patient after delivery also showed deposition of C4d along the glomerular capillary walls. CONCLUSIONS: C4d may play an important role in placental tissue injury and in renal complications in PE.