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Background Despite the widespread impact of the severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019, COVID-19) and vaccination in South Korea, our understanding of kidney diseases following these events remains limited. We aimed to address this gap by investigating the characteristics of glomerular diseases following the COVID-19 infection and vaccination in South Korea. Methods Data from multiple centers were used to identify de novo glomerulonephritis (GN) cases with suspected onset following COVID-19 infection or vaccination. Retrospective surveys were used to determine the COVID-19–related histories of patients who were initially not implicated. Bayesian structural time series and autoregressive integrated moving average models were used to determine causality. Results Glomerular diseases occurred shortly after the infection or vaccination. The most prevalent postinfection GN was podocytopathy (42.9%), comprising primary focal segmental glomerulosclerosis and minimal change disease, whereas postvaccination GN mainly included immunoglobulin A nephropathy (IgAN; 57.9%) and Henoch-Schönlein purpura nephritis (HSP; 15.8%). No patient progressed to end-stage kidney disease. Among the patients who were initially not implicated, nine patients with IgAN/HSP were recently vaccinated against COVID-19. The proportion of glomerular diseases changed during the pandemic in South Korea, with an increase in acute interstitial nephritis and a decrease in pauci-immune crescentic GN. Conclusion This study showed the characteristics of GNs following COVID-19 infection or vaccination in South Korea. Understanding these associations is crucial for developing effective patient management and vaccination strategies. Further investigation is required to fully comprehend COVID-19’s impact on GN.

Abstract CRISPR/Cas9 and Cas12a belonging to the Class II CRISPR system are characterized by a single-component effector protein. Despite unique features of Cas12a like DNA cleavage with 5′ staggered ends and a single crRNA, Cas12a has not been adopted in biotechnological applications to the similar extent as Cas9. To better understand the CRISPR/Cas12 systems, we selected two candidates, designated mgCas12a-1 and mgCas12a-2, from an analysis of the human microbiome metagenome (mg) and provided biochemical characterization. These new Cas12a proteins shared about 37% identity in amino acid sequences and shared the same direct repeat sequences in the crRNA with FnCas12a from Francisella novicida. The purification yield of the recombinant proteins was up to 3.6-fold greater than that of FnCas12a. In cell-free DNA cleavage assays, both mgCas12a proteins showed the higher cleavage efficiencies when Mn2+ was provided with KCl (

A 62-year-old man who presented with complaints of cough and hemoptysis was found to have an endobronchial tumor which obstructed the lingular bronchus. Histopathologic examination of a bronchoscopic biopsy of the tumor was consistent with malignant melanoma. Skin, mucosal, and eye examinations failed to detect the primary site of melanoma and the patient was diagnosed with endobronchial melanoma of unknown primary (MUP). Although the patient underwent a curative surgical resection, recurrence was detected in 4 months. Endobronchial MUP is a rare presentation of melanoma and better therapeutic strategies need to be established.

Melanotic oncocytic metaplasia (MOM) in the nasopharyngeal space is a very rare entity. Only 35 cases have been reported in the English literature, and most patients were East Asian males between 60 and 70 years of age. MOM presents as a brown or black lesion with slight elevation of the mucosa. These lesions are benign and defined as cellular enlargement with eosinophilic granular melanin-pigmented cytoplasm caused by mitochondrial accumulation. However, such presentation can lead physicians to misjudge MOM as a malignant lesion. Recently, we experienced a case of MOM of the nasopharynx. A 58-year-old woman was admitted to the internal medicine department with small-volume hemoptysis and referred to the ENT department for evaluation. She was a regular smoker without any medical history. Sinus endoscopy showed black pigmented lesions on both the torus tubaris and left posterior tonsillar pillar, with low bleeding risk. Excisional biopsy of the lesion was performed, and oncocytic metaplasia was confirmed pathologically. Hemoptysis showed spontaneous remission and no recurrence or other symptoms over 12 months of follow up. Melanotic oncocytic metaplasia in the nasopharynx should be clinically recognized to avoid misdiagnosis as a malignancy like melanoma.

V-set Ig domain-containing 4 (VSIG4) regulates an inflammatory response and is involved in various diseases. However, the role of VSIG4 in kidney diseases is still unclear. Here, we investigated VSIG4 expression in unilateral ureteral obstruction (UUO), doxorubicin-induced kidney injury mouse, and doxorubicin-induced podocyte injury models. The levels of urinary VSIG4 protein significantly increased in the UUO mice compared with that in the control. The expression of VSIG4 mRNA and protein in the UUO mice was significantly upregulated compared with that in the control. In the doxorubicin-induced kidney injury model, the levels of urinary albumin and VSIG4 for 24 h were significantly higher than those in the control mice. Notably, a significant correlation was observed between urinary levels of VSIG4 and albumin (r = 0.912, p < 0.001). Intrarenal VSIG4 mRNA and protein expression were also significantly higher in the doxorubicin-induced mice than in the control. In cultured podocytes, VSIG4 mRNA and protein expressions were significantly higher in the doxorubicin-treated groups (1.0 and 3.0 μg/mL) than in the controls at 12 and 24 h. In conclusion, VSIG4 expression was upregulated in the UUO and doxorubicin-induced kidney injury models. VSIG4 may be involved in pathogenesis and disease progression in chronic kidney disease models.

Polymer piezoelectric devices have been widely studied as sensors, energy harvesters, and generators with flexible and simple processes. Flexible piezoelectric devices are sensitive to external stimuli and are attracting attention because of their potential and usefulness as acoustic sensors. In this regard, the frequency sensing of sound must be studied to use flexible piezoelectric devices as sensors. In this study, a flexible piezoelectric device composed of a polymer and an electrode was successfully fabricated. Polyvinylidene fluoride, the active layer of the piezoelectric device, was prepared by electrospinning, and electrodes were formed by dip−coating in a prepared single−walled carbon nanotube dispersion. The output voltage of the external sound was matched with the input frequency through a fast Fourier transform, and frequency matching was successfully performed, even with mechanical stimulation. In a high−frequency test, the piezoelectric effect and frequency domain peak started to decrease sharply at 300 Hz, and the limit of the piezoelectric effect and sensing was observed from 800 Hz. The results of this study suggest a method for developing flexible piezoelectric-fiber frequency sensors based on piezoelectric devices for acoustic sensor systems.

Diffuse involvement of colorectal lymphoma masquerading as colitis is a very rare presentation of primary colorectal lymphoma. Detecting occult lymphoma is difficult in the setting of diffuse colonic involvement with no definite mass and inflammatory mucosal changes. We encountered a case of diffuse-type primary colorectal lymphoma simulating ulcerative colitis in a previously healthy 31-year-old woman. Despite multiple mucosal biopsies, the biopsy diagnosis was not made due to unawareness of atypical lymphocytes admixed with dense lymphoplasmacytic infiltration. The present case emphasizes the importance of being aware of this rare presentation of primary colorectal lymphoma in order to avoid misdiagnosis.

Fibrosis is the final common finding in patients with advanced diabetic kidney disease. V-set Ig domain containing 4 (VSIG4) is related to fibrosis in several diseases. It also contributes to fibrosis under high-glucose conditions in renal tubule cells. To determine the role of VSIG4 in type 2 diabetes, we examined VSIG4 expression in a type 2 diabetic animal model and podocyte. Urinary excretion of albumin and VSIG4 was significantly higher in db/db mice than in the control group. Urine VSIGs levels for 6 h were about three-fold higher in db/db mice than in db/m mice at 20 weeks of age: 55.2 ± 37.8 vs. 153.1 ± 74.3 ng, p = 0.04. Furthermore, urinary VSIG4 levels were significantly correlated with urinary albumin levels (r = 0.77, p < 0.01). Intrarenal VSIG4 mRNA expression was significantly higher in db/db mice than in control mice (1.00 ± 0.35 vs. 1.69 ± 0.77, p = 0.04). Further, VSIG4 expression was almost twice as high in db/db mice at 20 weeks of age. Intrarenal VSIG immunoreactivity in db/db mice was also significantly higher than that in control mice. In cultured podocytes, both high glucose and angiotensin II significantly upregulated the expression of VSIG4 mRNA and protein. In conclusion, VSIG4 was upregulated in an animal model of type 2 diabetes and was related to albuminuria and pro-fibrotic markers. Considering these relationships, VSIG4 may be an important mediator of diabetic nephropathy progression.

Primary mediastinal leiomyoma is an extremely rare benign tumor of smooth muscle. Most common radiographic appearance is a well circumscribed heterogeneous solid mass. We reported a case of giant cyst-like lesion at the middle mediastinum, which was pathologically confirmed as a primary mediastinal leiomyoma.

Background: Since 2003, the Korean Society of Pathologists (KSP) has been officially providing medical advisory services (MAS). We reviewed the cases submitted to the KSP between 2003 and 2014. Methods: In total, 1,950 cases were submitted, most by private health insurance companies. The main purposes of the consultations were to clarify the initial diagnoses and to assign a proper disease classification code. We comprehensively reviewed 1,803 consultation cases with detailed information. Results: In spite of some fluctuations, the number of submitted cases has been significantly increasing over the 12 study years. The colon and rectum (40.3%), urinary bladder (14.2%), and stomach (6.9%) were the three most common tissues of origin. The most common diagnoses for each of the three tissues of origin were neuroendocrine tumor (50.7%), non-invasive papillary urothelial carcinoma (70.7%), and adenocarcinoma (36.2%). Regardless of the tissue of origin, neuroendocrine tumor of the digestive system was the most common diagnosis (419 of 1,803). Conclusions: In the current study, we found that pathologic consultations associated with private health insurance accounted for a large proportion of the MAS. Coding of the biologic behavior of diseases was the main issue of the consultations. In spite of the effort of the KSP to set proper guidelines for coding and classification of tumors, this review revealed that problems still exist and will continue to be an important issue.

The use of metal-organic frameworks (MOFs) to solve problems, like environmental pollution, disease, and toxicity, has received more attention and led to the rapid development of nanotechnology. In this review, we discuss the basis of the metal-organic framework as well as its application by suggesting an alternative of the present problem as catalysts. In the case of filtration, we have developed a method for preparing the membrane by electrospinning while using an eco-friendly polymer. The MOFs were usable in the environmental part of catalytic activity and may provide a great material as a catalyst to other areas in the near future.

Background Angioleiomyoma, a vascular leiomyoma, is a rare, benign smooth-muscle tumor that originates in the tunica media of vessels. It occurs anywhere in the body, most frequently in the lower extremities. Methods We reviewed the medical records of 16 patients who were treated for angioleiomyoma between 2000 and 2012. The clinical features of angioleiomyoma and the correlation between symptoms and pathological subtypes were investigated. Results There were 9 males and 6 females. Ages of the patients ranged from 21 to 61. Pain was the primary symptom in 44% of the patients. Tumors were smaller than 2.0 cm in all dimensions and were located in the face in 4 patients, whereas 5 lesions occurred in the upper extremities and the remaining 7 in the lower extremities. Three histologic subtypes were identified: solid, venous, and cavernous. The subtypes did not correlate with the clinical symptoms. Conclusions Angioleiomyoma appears to be a rare tumor that occurs in the face and the extremities. The tumor usually occurs in middle age. A differential diagnosis of this tumor is difficult, but the tumor should be considered in the diagnosis of painful subcutaneous masses. Ultrasonography and magnetic resonance imaging can be helpful in the diagnosis of angioleiomyoma. These tumors can be successfully treated with simple excision, with a low recurrence rate.

Lack of bone formation-related health problems are a major problem for the aging population in the modern world. As a part of the ongoing trend of developing natural substances that attenuate osteoporotic bone loss conditions, dioxinodehydroeckol (DHE) from edible brown alga Ecklonia cava was tested for its effects on osteoblastogenic differentiation in MC3T3-E1 pre-osteoblasts. DHE was observed to successfully enhance osteoblast differentiation, as indicated by elevated cell proliferation, alkaline phosphatase activity, intracellular cell mineralization, along with raised levels of osteoblastogenesis indicators at the concentration of 20 μM. Results suggested a possible intervening of DHE on the bone morphogenetic protein (BMP) signaling pathway, according to elevated protein levels of BMP-2, collagen-I, and Smads. In addition, the presence of DHE was also able to raise the phosphorylated extracellular signal–regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) levels which are also activated by the BMP signaling pathway. In conclusion, DHE is suggested to be a potential bioactive compound against bone loss that could enhance osteoblastogenesis with a suggested BMP pathway interaction.

Solitary fibrous tumor (SFT) is an uncommon neoplasm of mesenchymal origin, and it most often occurs in the pleura. Mammary gland involvement is extremely rare in this disease. Herein, we report a case of SFT that presented as a slowly growing large mass in the breast of a 64-year-old man. On ultrasonographic examination, the mass was oval and circumscribed with heterogeneous echogenicity and increased intralesional blood flow. Moreover, the mass showed hard elasticity as revealed by shear-wave elastography (SWE), which has not been reported in English literature so far. We also briefly review the literature on the radiologic findings. Because of the nonspecific imaging findings and difficulty in its differentiation from other soft tissue tumors, complete excision with detailed immunohistochemistry is essential. [ABSTRACT FROM AUTHOR]

Lack of bone formation-related health problems are a major problem for the aging population in the modern world. As a part of the ongoing trend of developing natural substances that attenuate osteoporotic bone loss conditions, dioxinodehydroeckol (DHE) from edible brown alga Ecklonia cava was tested for its effects on osteoblastogenic differentiation in MC3T3-E1 pre-osteoblasts. DHE was observed to successfully enhance osteoblast differentiation, as indicated by elevated cell proliferation, alkaline phosphatase activity, intracellular cell mineralization, along with raised levels of osteoblastogenesis indicators at the concentration of 20 μM. Results suggested a possible intervening of DHE on the bone morphogenetic protein (BMP) signaling pathway, according to elevated protein levels of BMP-2, collagen-I, and Smads. In addition, the presence of DHE was also able to raise the phosphorylated extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) levels which are also activated by the BMP signaling pathway. In conclusion, DHE is suggested to be a potential bioactive compound against bone loss that could enhance osteoblastogenesis with a suggested BMP pathway interaction. [ABSTRACT FROM AUTHOR]

Background aims. Graft-versus-host disease (GvHD) remains a major complication after allogeneic hematopoietic cell transplantation (HCT). Recent literature demonstrates a potential benefit of human mesenchymal stromal cells (MSC) for the treatment of refractory GvHD; however, the optimal dose remains uncertain. We set out to develop an animal model that can be used to study the effect of MSC on GvHD. Methods. A GvHD mouse model was established by transplanting C3H/he donor bone marrow (BM) cells and spleen cells into lethally irradiated BALB/c recipient mice. MSC were obtained from C3H/he mice and the C3H/10T1/2 murine MSC line. Results. The mRNA expression of Foxp3 in regional lymph nodes (LN) localized with T cells was markedly increased by the addition of C3H10T1/2 cells in a real-time polymerase chain reaction (PCR). Using a mixed lymphocyte reaction, we determined the optimal splenocyte proliferation inhibition dose (MSC:splenocyte ratios 1:2 and 1:1). Three different C3H10T1/2 cell doses (low, 0.5 × 106, intermediate, 1 × 106, and high, 2 × 106) with a consistent splenocyte dose (1 × 106) were evaluated for their therapeutic potential in an in vivo GvHD model. The clinical and histologic GvHD score and Kaplan–Meier survival rate were improved after MSC transplantation, and these results demonstrated a dose-dependent inhibition. Conclusions. We conclude that MSC inhibit GvHD in a dose-dependent manner in this mouse model and this model can be used to study the effects of MSC on GvHD. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 38-year-old woman who was treated for trichoblastic carcinoma in her nevus sebaceous.

The article presents a study on the electrospinning jet behavior of polyvinyl alcohol with various nozzle diameters. According to the study, multi-jet ejections were related to the amount of nanoweb deposition and the deposition pattern. The study found that a gradual increase in the multi-jet ejection with increasing applied voltage was induced by increased electrical stress in electrospinning with smaller nozzle diameter. Decreasing nozzle diameter and increasing applied voltage decreased the diameter of the deposited fiber.

Aims: To investigate whether the GnRH agonist may reduce aromatase P450 and COX-2 in the eutopic endometrium of patients with endometriosis and ovarian endometrioma. Materials and Methods: Endometrial specimens and ovarian endometrioma were obtained from 15 women with endometriosis undergoing laparoscopic surgery. The stromal cells of the eutopic endometrium and ovarian endometroma were cultured in the presence of the GnRH agonist (leuprolide acetate 0, 1, 5 and 10 μM) for 24 h. To investigate the effects of the GnRH agonist on the eutopic endometrium in vivo, biopsy samples of the endometrium (n = 5) among the patients who underwent laparoscopy were obtained after GnRH agonist therapy. The protein production of aromatase cytochrome P450 and COX-2 was examined by Western blot. Results: Proteins of aromatase P450 and COX-2 were reduced in the eutopic endometrium of patients with endometriosis treated with the GnRH agonist for 3 months. The stromal cells in the culture of endometrial explants and ovarian endometrioma which were treated with the GnRH agonist reduced the aromatase P450 and COX-2. Conclusion: The GnRH agonist reduced aromatase P450 and COX-2 by direct action on the eutopic endometrium of patients with endometriosis and ovarian endometrioma. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

This study addresses the three-dimensional structure and mechanical properties of perpendicular-laid nonwovens produced from PET and PET/PE bicomponent fibers. Two different web-forming methods, air folding and mechanical folding systems, have been employed to produce the perpendicular-laid nonwovens. It is proved that both systems can produce well-developed perpendicular-laid structures. A comparison has been made between mechanical properties and fiber orientation distribution function (ODF). ODFs at three faces of nonwovens were analyzed by image analysis techniques using the two-dimensional Fast Fourier Transform (2D FFT). Further, mechanical measurements were performed at various azimuthal directions to investigate the related mechanical responses in three-dimensions. [ABSTRACT FROM AUTHOR]

Tumoral calcinosis is a rare ectopic calcification syndrome characterized by irregular soft tissue masses originally described as being found mainly in large joints. We report 3 cases of tumoral calcinosis that occurred in unusual locations, the metacarpophalageal and proximal interphalangeal joints of the hand. The patients were women who ranged in age from 26 to 44; all presented with complaints of painful swelling of the joints. Laboratory tests demonstrated normal serum phosphate and calcium levels. Radiologic examination disclosed para-articular calcified masses. On surgical excision, the deep-seated calcified masses were attached to collateral ligaments of the joints. Milky and chalklike fluid was released during surgery. The masses measured 1.5, 0.9, and 0.8 cm in length and had irregular surfaces. Microscopically, the masses had fibrous capsule and the inner small cystic spaces that contained granular, calcified material. These cysts contained proliferating capillaries, mononuclear lymph plasma cells, and giant cells. No recurrences were found in any of the patients during the follow-up periods. [ABSTRACT FROM AUTHOR]

A case of perivascular epithelioid cell tumor of the uterus is reported, occurring in a 32-year-old woman. The tumor (8.0 cm in dimension) showed exophytic growth from the outer half of the myometrium. Histopathologically, the tumor was composed of thick blood vessels and perivascular epithelioid cells. The neoplastic cells were strongly immunoreactive for HMB45 antigen, CD117 (c-kit), vimentin and the progesterone receptor, but completely negative for S-100 protein, smooth muscle actin, desmin, CD34, the estrogen receptor and p16. The Ki-67 labeling index was low (1.25%). Ultrastructurally, the neoplastic cells had numerous premelanosomes with some glycogen deposits. Single-stranded DNA conformational polymorphism of p53 and methylation-specific polymerase chain reaction of p16 revealed negative results. Definite melanosomes on electron microscopic analysis and coexpression of HMB45 antigen and stem cell factor receptor (CD117) may provide the clue to understanding perivascular epithelioid cell tumor because angiomyolipoma also coexpresses HMB45 antigen and CD117. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 4-year-old patient with intratympanic membrane congenital cholesteatoma (IMCC) who underwent IMCC removal using an endoscopic system. Topics covered include the result of the computed tomography scan conducted on the patient, findings of a systematic review which supported the presumption that IMCC is congenital and the first choice for treatment of IMCC.

Few data exist regarding steroid withdrawal in ABO-incompatible (ABO-i) kidney transplantation (KT). Here, we report a case of steroid withdrawal after ABO-i KT. A 46-year-old man diagnosed with Henoch-Schonlein purpura received ABO-i KT from his 42-year-old sister. The recipient and donor blood types were O and AB, respectively. His preoperative ABO antibody titers were anti-A of 1:16 and anti-B of 1:8 in isoagglutinin test. HLA mismatch was 0 and he received a single 325 mg/m2 dose of intravenous (IV) rituximab 4 weeks before KT. Three sessions of plasma exchange were undertaken before KT and low-dose IV immunoglobulin of 0.1 g/kg was administered after plasma exchange. On the day of the operation, ABO antibody titer decreased to anti-A of 1:4 and anti-B of 1:2. Renal function remained stable after KT. The patient wished to stop steroid treatment despite the risk of rejection after withdrawal. Steroid tapering was initiated at 20 months and accomplished at 26 months after KT. At that time, serum creatinine level was 1.13 mg/dL, and anti-A and anti-B titers were 1:8 and 1:2, respectively. No issues were observed after steroid withdrawal. At 48 months after KT, serum creatinine level was 1.21 mg/dL, and anti-A and anti-B antibody titers were 1:32 and 1:2, respectively. Steroid withdrawal in ABO-i KT might be considered in immunologically low-risk patients.

Esophageal cancer is one of the lethal malignant tumors because it is often diagnosed in the advanced stage with lymph node or distant metastasis. The recurrence rate of esophageal cancer is known to be about 40% to 50% even in the patients who underwent curative esophageal resection. Most frequent sites of metastases are known to be the liver. Furthermore, other distant metastases also could be developed in lung, bone, brain, kidney, adrenal, abdominal cavity, and skin. However, ampulla of Vater (AoV) metastasis rarely occurs from esophageal cancer. Therefore, we report herein a case of AoV metastasis from squamous cell carcinoma of the esophagus.

Cancer: Tell-tale signs of recurrence Fragments of tumor DNA, or circulating tumor DNA (ctDNA), in blood can help predict stomach cancer recurrence within 12 months of surgery. Kyeong-Man Hong at the National Cancer Center, in Goyang-si, South Korea, and colleagues, carried out whole genome sequencing of stomach tumor samples from 25 patients to identify personalized cancer-specific rearranged DNA sequences. When they used this information to monitor ctDNA in blood samples obtained after surgical removal of the tumor, they found a significant correlation between the presence of ctDNA and cancer recurrence. In most cases, ctDNA was detected around four months prior to clinical recurrence, highlighting the potential usefulness of ctDNA monitoring. The lack of correlation between ctDNA levels and tumor size suggests that further research into the factors determining ctDNA levels is needed.

Abstract Background Primary renal well-differentiated neuroendocrine tumors (WDNETs) also called carcinoid and atypical carcinoid are extremely rare, and little is known about parameters that may predict prognosis at diagnosis. Methods Six cases of primary renal WDNET were collected. After reviewing slides stained with hematoxylin and eosin, proportions of each growth pattern were determined. Synaptophysin, chromogranin, CD56, and Ki-67 immunostaining and Ki-67 morphometric analysis were performed. Results Patients included three female and three males, mean age was 53.3 years. The mean tumor size was 4.5 cm, three cases were greater than 5 cm. At the time of initial surgery, lymph node and/or distant metastasis was confirmed in two cases. In a third case, no metastasis was initially found, but lymph node metastasis was identified during follow-up. The remaining three cases did not exhibit metastasis. Histopathologically, the renal WDNETs were primarily composed of ribbon-like and sheet-like growth patterns. Most of the tumors were diffusely positive for neuroendocrine markers. Mitotic count was high (≥2/10HPF) in cases with lymph node or distant metastasis but was low (

Multiple wasp stings can induce multiple organ dysfunction by toxic reactions. However, acute pancreatitis is a rare manifestation in wasp sting injury. A 74-year-old woman visited the emergency department by anaphylactic shock because of multiple wasp stings. Acute kidney injury, rhabdomyolysis, hepatotoxicity, and coagulopathy were developed next day. Serum amylase and lipase were elevated and an abdominal computed tomography revealed an acute pancreatitis. Urine output was recovered after 16 days of oliguria (below 500 ml/day). Her kidney, liver, and pancreas injury gradually improved after sessions of renal replacement therapy.

Recently, we reported cytoskeleton-associated protein2 (CKAP2) as a possible new prognostic breast cancer marker. However, it has not yet been applied in clinic. Therefore, clinical significance of CKAP2 was evaluated in comparison with that of Ki-67 in a cohort of breast cancer patients, and the expression difference was analyzed in cell cycle-arrested cancer and fibroblast cells.A total of 579 early breast cancer patients who underwent surgery at the National Cancer Center Hospital in Korea between 2001 and 2005 were accrued. CKAP2-positive cell count (CPCC) and Ki-67 labeling index (Ki-67LI) were evaluated by immunohistochemcal staining. The immunocytochemical staining patterns of CKAP2 and Ki-67 were analyzed in HeLa and human fibroblast cells after synchronization by double thymidine block.Although there was a significant correlation (R = 0.754, P < 0.001) between CPCC and Ki-67LI, only CPCC was correlated with DFS in overall population (HR, 2.029; 95% CI, 1.012-4.068; P = 0.046) and HER2-negative luminal subgroup (HR, 3.984; 95% CI, 1.350-11.762; P = 0.012) by multivariate analysis. In immunocytochemical staining, more than 50% of serum-starved or non-mitotic cell phase HeLa cells were positive for Ki-67, in comparison to the low CKAP2-positivity, which might explain the prognostic difference between CPCC and Ki-67LI.The current study showed that CPCC but not Ki-67LI is an independent prognostic indicator in early breast cancer, more specifically in HER2-negative luminal breast cancer. The difference between two markers may be related to the lower background expression of CKAP2 in cancer cells.

BACKGROUND: The level of proliferation activity is a strong prognostic or predictive indicator in breast cancer, but its optimal measurement is still in debate, necessitating new proliferation markers. In the present study, the prognostic significance of the CKAP2-positive cell count (CPCC), a new proliferation marker, was evaluated, and the results were compared with those for the mitotic activity index (MAI). METHODS: This study included 375 early-stage breast cancer samples collected from two institutions between 2000 and 2006. Immunohistochemical staining was performed using a CKAP2 monoclonal antibody. Cox proportional hazard regression models were fitted to determine the association between the CPCC and relapse-free survival (RFS) amongst three groups formed on the basis of the CPCC or MAI value: groups 2 and 3 showing the middle and highest values, respectively, and group 1 the lowest. RESULTS: After adjustment for age, T stage, N stage, HER2 status, estrogen receptor status, progesterone receptor status, institution, and year of surgical resection, the CPCC was associated with a significantly worse RFS {hazard ratio [HR] = 4.10 (95% CI: 1.64-10.29) for group 2; HR = 4.35 (95% CI: 2.04-10.35) for group 3}. Moreover, its prognostic significance was similar to or higher than that based on the MAI {HR = 2.05 (95% CI: 0.94-4.65) for group 2; HR = 2.35 (95% CI: 1.09-5.10) for group 3}. In subgroup analyses, the CPCC showed a prognostic significance in the luminal A and triple-negative subgroups, but not in the HER2-positive subgroup. CONCLUSIONS: Chromatin CKAP2 is an independent prognostic marker for RFS in early-stage breast cancer, and could potentially replace the MAI in clinical evaluation of proliferation activity. Additionally, our study results suggest that the prognostic significance of proliferation activity differs among the various subgroups of breast cancer.

Variations and alterations of copy numbers (CNVs and CNAs) carry disease susceptibility and drug responsiveness implications. Although there are many molecular methods to measure copy numbers, sensitivity, reproducibility, cost, and time issues remain. In the present study, we were able to solve those problems utilizing our modified real competitive PCR method with cloned competitors (mrcPCR). First, the mrcPCR for ERBB2 copy number was established, and the results were comparable to current standard methods but with a shorter assay time and a lower cost. Second, the mrcPCR assays for 24 drug-target genes were established, and the results in a panel of NCI-60 cells were comparable to those from real-time PCR and microarray. Third, the mrcPCR results for FCGR3A and the FCGR3B CNVs were comparable to those by the paralog ratio test (PRT), but without PRT's limitations. These results suggest that mrcPCR is comparable to the currently available standard or the most sensitive methods. In addition, mrcPCR would be invaluable for measurement of CNVs in genes with variants of similar structures, because combination of the other methods is not necessary, along with its other advantages such as short assay time, small sample amount requirement, and applicability to all sequences and genes.