A Nationwide Study on HER2-low Breast Cancer in South Korea: Its Incidence of 2022 Real World Data and the Importance of Immunohistochemical Staining Protocols.

Purpose: Notable effectiveness of trastuzumab deruxtecan (T-DXd) in patients with HER2-low advanced breast cancer (BC) has focused pathologists' attention. We studied the incidence and clinicopathologic characteristics of HER2-low BC, and the effects of immunohistochemistry (IHC) associated factors on HER2 IHC results. Materials and Methods: The Breast Pathology Study Group of the Korean Society of Pathologists conducted a nationwide study using real-world data on HER2 status generated between January 2022 and December 2022. Information on HER2 IHC protocols at each participating institution was also collected. Results: Total 11,416 patients from twenty-five institutions included in this study. Of these patients, 40.7% (range: 6.0%-76.3%) were classified as HER2-zero, 41.7% (range: 10.5%-69.1%) as HER2-low, and 17.5% (range: 6.7%-34.0%) as HER2-positive. HER2-low tumors were associated with positive ER and PR statuses (p<0.001 and p<0.001, respectively). Antigen retrieval times (≥ 36 min vs. < 36 min) and antibody incubation times (≥ 12 min vs. < 12 min) affected on the frequency of HER2 IHC 1+ BC at institutions using the PATHWAY HER2 (4B5) IHC assay and BenchMark XT or Ultra staining instruments. Furthermore, discordant results between core needle biopsy (CNB) and subsequent resection specimen HER2 statuses were observed in 24.1% (787/3259) of the patients. Conclusion: The overall incidence of HER2-low BC in South Korea concurs with those reported in previously published studies. Significant inter-institutional differences in HER2 IHC protocols were observed, and it may have impact on HER2-low status. Thus, we recommend standardizing HER2 IHC conditions to ensure precise patient selection for targeted therapy.

Scalp nodules as the first presentation of prostate cancer: A CARE-compliant article.

RATIONALE: Bones are the most common site of prostate cancer metastasis. Other common sites of metastases include the distant lymph nodes, liver, thorax, brain, and digestive system. However, cutaneous metastases from prostate cancer are extremely rare. PATIENT CONCERNS: We present a case of a 61-year-old man with scalp nodules without any cancer history. DIAGNOSIS: The patient was diagnosed with metastatic prostate adenocarcinoma through an incisional biopsy for his scalp nodules. The patient presented with a serum prostate-specific antigen level of 10.2 ng/mL; imaging examinations revealed extraprostatic extension, lymph node involvement, and multiple bone metastases. INTERVENTION: The patient was treated with androgen deprivation therapy with leuprolide acetate (7.5 mg every month) and abiraterone acetate (1000 mg daily). OUTCOMES: The scalp metastases resolved without adverse effects, and the serum prostate-specific antigen level decreased to 0.02 ng/mL. LESSONS: Cutaneous metastasis, especially scalp metastasis from prostate cancer, is extremely rare. If there is a rash or nodule on the skin, it is necessary to evaluate it carefully and to confirm it through a biopsy.

A Case of Intracranial Solitary Fibrous Tumor/Hemangiopericytoma Repeatedly Misdiagnosed as Hypertensive Intracerebral Hemorrhage.

Because solitary fibrous tumor (SFT) and hemangiopericytoma (HPC) contain identical genetic abnormalities, the World Health Organization coined the term SFT/HPC to describe these lesions. Here, we present a rare case of SFT/HPC in a 40-year-old man with massive repeated intracranial hemorrhage (ICH) in right medial temporal lobe. ICHs from a SFT/HPC were repeatedly misdiagnosed as hypertensive ICH by several departments and hospitals over approximately eight months, and the patient underwent inappropriate treatments. The amount of repeated ICH accompanying the tumor has increased significantly compared to the first ICH, which may suggest rapid tumor growth. To avoid misdiagnosis and inappropriate treatment, surgeons should carefully examine all past and current patient-related radiological images and medical records before considering surgery.

Evaluating the Relationship Between Dynamic Contrast-Enhanced MRI (DCE-MRI) Parameters and Pathological Characteristics in Breast Cancer.

BACKGROUND: Dynamic contrast-enhanced MRI (DCE-MRI) is used to evaluate tumor microvasculature. However, studies demonstrating an association between perfusion parameters derived from DCE-MRI and histopathologic characteristics are limited to a small set of histopathologic factors, and the results are inconsistent. PURPOSE: To evaluate the relationship between DCE-MRI perfusion parameters and common histopathologic tumor characteristics used to predict angiogenesis and determine prognosis in breast cancer. STUDY TYPE: Retrospective. POPULATION: In all, 105 breast cancer patients with invasive ductal carcinoma (122 lesions). FIELD STRENGTH/SEQUENCE: 3.0T, turbo spin-echo (TSE) T1 -weighted, fat-suppressed T2 -weighted, TSE T2 -weighted, and dynamic unenhanced and contrast-enhanced 3D T1 high-resolution isotropic volume examination. ASSESSMENT: One reviewer obtained perfusion parameters (Ktrans , kep , ve , and vp ) of each breast cancer from DCE MRI using the extended Tofts model with a fixed baseline T1 value and a population-based arterial input function. The relationship between DCE-MRI perfusion parameters and histopathologic tumor characteristics used to predict angiogenesis and determine prognosis was evaluated. STATISTICAL TESTS: Student's t-test, Mann-Whitney U-test, analysis of variance (ANOVA), and Kruskal-Wallis test were used. RESULTS: Triple-negative breast cancers exhibited higher Ktrans and kep than luminal cancers (P < 0.05). Estrogen receptor (ER)-negative tumors showed higher Ktrans than ER-positive tumors (P < 0.05). Progesterone receptor (PR)-negative tumors presented higher ve than PR-positive tumors (P < 0.05). Tumors with higher Ki-67 showed higher kep than tumors with lower Ki-67 (P < 0.05). P53-positive tumors exhibited higher Ktrans and kep than p53-negative tumors (P < 0.05). Higher histologic grade tumors (grade II/III) presented higher Ktrans , kep , vp (P < 0.05) than grade I tumors. Tumors with LVSI presented higher Ktrans and kep than tumors without LVSI (P < 0.05). DATA CONCLUSION: Breast cancer presenting higher Ktrans and kep on DCE-MRI was associated with poor prognostic histopathologic factors. Therefore, pretreatment DCE-MRI perfusion parameters may be useful imaging biomarkers for the evaluation of tumor prognosis and angiogenesis. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

Recurrent KRAS mutations identified in papillary renal neoplasm with reverse polarity-a comparative study with papillary renal cell carcinoma.

Comprehensive molecular analyses revealed that papillary renal cell carcinoma (PRCC) is a heterogenous entity. Papillary renal neoplasm with reverse polarity (PRNRP) is a subset of PRCC with characteristic histomorphologies such as low-grade nuclear features, inverted nuclear location, eosinophilic cytoplasm, and indolent clinical behavior. We tried to define the molecular, clinicopathological, histologic, and immunohistochemical features of PRNRP by comparing them with type 1 PRCC (PRCC1) and type 2 PRCC (PRCC2). A cohort of 30 PRNRP, 23 PRCC1, and 26 PRCC2 cases was used. Targeted sequencing of 90 cancer-related genes including KRAS was performed in 26 PRNRP tumor samples. PNA-mediated clamping PCR of KRAS was performed using paired normal and tumor DNA from 30 PRNRP, 23 PRCC1, and 26 PRCC2 cases. Tissue microarray slides were made in three cores per tumor, which were stained with cytokeratin 7 (CK7), alpha-methylacyl-CoA racemase (AMACR), epithelial membrane antigen (EMA), E-cadherin, vimentin, and CD10. Recurrent mutations in KRAS were detected in 28 of the 30 PRNRPs. However, there were no KRAS mutations in any PRCC1 or PRCC2 cases. PRNRP exhibited distinct clinicopathological features: small tumor size, lower pathologic T stage, and no disease-specific death during the follow-up period. Histologically, peritumoral lymphoid aggregation, prominent papillary architecture (>80% of tumor), hyalinized papillae, inverted nuclear location, and lower nuclear grade were observed. PRNRP was usually positive for CK7, AMACR, EMA, and E-cadherin, and negative for CD10. The findings suggest that PRNRP is a subtype of papillary renal neoplasm that is different from PRCC1 or PRCC2 in terms of molecular, clinicopathological, histological, and immunohistochemical features.

MicroRNA 375 regulates proliferation and migration of colon cancer cells by suppressing the CTGF-EGFR signaling pathway.

MicroRNA 375 (MIR375) is significantly down regulated in human colorectal cancer (CRC) tissues; we have previously identified MIR375 as a colon cancer associated microRNA (miRNA). We identified putative MIR375 target genes by comparing the mRNA microarray analysis data of MIR375-overexpressing cells with the candidate MIR375 target genes predicted by public bioinformatic tools. We investigated that the connective tissue growth factor (CTGF) is a direct target gene of MIR375. Expression of CTGF, a ligand of epidermal growth factor receptor (EGFR), was markedly enhanced in human CRC tissues in comparison with the corresponding normal colon tissues. We demonstrated that the expression levels of molecules in EGFR signaling pathways were regulated by MIR375 in colorectal cells. Using immunohistochemistry and the xenograft of MIR375-overexpressing colorectal cells in mice, we showed that MIR375 regulates cell growth and proliferation, angiogenesis, cell migration, cell cycle arrest, apoptosis, and necrosis in colon cells. Furthermore, results of MIR375 overexpression and cetuximab treatment indicated that the apoptosis and necrosis in colon cells were synergistically enhanced. Our results suggest that the down-regulation of MIR375 modulates EGFR signaling pathways in human colorectal cells and tissues by increasing CTGF expression; therefore, MIR375 may have a therapeutic value in relation to human CRC.

Aggressive Imaging Features in a Malignant Pheochromocytoma With a Novel Mutation of the SDHB Gene.

We describe a 15-year-old boy with a huge bilateral adrenal pheochromocytoma that had a de novo germline mutation in the succinate dehydrogenase subunit B (SDHB) gene. F-FDG PET/CT revealed bilateral metabolically active large masses in the adrenal glands and the activated brown adipose tissues. The I-MIBG scintigraphic findings revealed only a mild accumulation of MIBG in the right adrenal mass, but a high uptake in the left adrenal mass. Thus, F-FDG PET/CT imaging may be more effective than I-MIBG scintigraphy for the evaluation of pheochromocytomas that are associated with highly malignant characteristics resulting from mutations of the SDHB gene.

Extrathyroidal Radioiodine Accumulation in a Fibroadenoma of the Breast.

A 45-year-old woman with a differentiated thyroid carcinoma received adjuvant radioiodine therapy following total thyroidectomy and left modified radical neck dissection. A posttherapy planar radioiodine scan showed multifocal uptake in the thyroid bed and left chest. SPECT/CT revealed a fibroadenoma in the left breast. Six months later, an I scan showed no iodine avidity in the breast fibroadenoma, whereas ultrasonography showed no significant change in the size of the fibroadenoma. Altered radioiodine uptake of a breast fibroadenoma can be observed on follow-up scans after cytotoxic radioiodide treatment in patients with differentiated thyroid carcinoma.

MicroRNA 429 Regulates Mucin Gene Expression and Secretion in Murine Model of Colitis.

BACKGROUND AND AIMS: miRNAs are non-coding RNAs that play important roles in the pathogenesis of human diseases by regulating target gene expression in specific cells or tissues. We aimed to detect miRNAs related to ulcerative colitis [UC], identify their target molecules, and analyse the correlation between the miRNAs and their target genes in colorectal cells and dextran sulphate sodium [DSS]-induced mouse colitis. METHODS: UC-associated miRNAs were identified by miRNA microarray analysis using DSS-induced colitis and normal colon tissues. The results were validated by quantitative real-time polymerase chain reaction [RT-PCR]. We identified target genes of MIR429, a colitis-associated miRNA, from our screen by comparing the mRNA microarray analysis in MIR429-overexpressed cells with predicted candidate target genes. We constructed luciferase reporter plasmids to confirm the effect of MIR429 on target gene expression. The protein expression of the target genes was measured by western blot,enzyme-linked immunosorbent assay [ELISA] analysis, or immunohistochemistry. RESULTS: We identified 37 DSS-induced colitis associated miRNAs. We investigated MIR429 that is down-regulated in DSS-induced colitis, and identified 41 target genes of MIR429. We show that the myristoylated alanine-rich protein kinase C substrate [MARCKS] is a direct target of MIR429. MARCKS mRNA and protein expression levels are down-regulated by MIR429, and MIR429 regulates the expression of MARCKS and MARCKS-mediated mucin secretion in colorectal cells and DSS-induced colitis. In addition, anti-MIR429 up-regulates MARCKS expression in colorectal cell lines. CONCLUSION: Our findings suggest that MIR429 modulates mucin secretion in human colorectal cells and mouse colitis tissues by up-regulating of MARCKS expression, thereby making MIR429 a candidate for anti-colitis therapy in human UC.

The Association of the GABRP Polymorphisms with Systemic Lupus Erythematosus.

Gamma-aminobutyric acid receptor subunit pi (GABRP) is involved in inhibitory synaptic transmission in the central nervous system. This gene encodes multisubunit chloride channels and is also expressed in numerous nonneuronal tissues such as the uterus and the ovaries. This study was aimed to validate whether the polymorphisms in the GABRP gene are associated with the susceptibility to systematic lupus erythematosus (SLE). The genotype frequencies of the rs929763, rs732157, and rs3805455 of the GABRP gene in SLE patients were significantly different from those of the control group (P < 0.0001, P = 0.05 and 0.002, resp.). Additional analysis showed that the genotype of the rs929763 and rs3805455 of the GABRP gene were also significantly associated with female SLE patients (P < 0.0001, P = 0.005, resp.). Two haplotype frequencies including a major haplotype of GABRP SNPs were more significantly different between the SLE patients and the healthy controls (P = 0.038 and 4.2E - 24, resp.). These results suggest that the polymorphisms in the GABRP gene might be associated with the susceptibility to SLE and the haplotype of GABRP SNPs is useful genetic marker for SLE.

Are Irregular Hypoechoic Breast Masses on Ultrasound Always Malignancies?: A Pictorial Essay.

Irregular hypoechoic masses in the breast do not always indicate malignancies. Many benign breast diseases present with irregular hypoechoic masses that can mimic carcinoma on ultrasonography. Some of these diseases such as inflammation and trauma-related breast lesions could be suspected from a patient's symptoms and personal history. Careful ultrasonographic examination and biopsy could help to differentiate these from malignancies.

The TGF-ß Signaling Regulator PMEPA1 Suppresses Prostate Cancer Metastases to Bone.

Transforming growth factor-ß (TGF-ß) regulates the expression of genes supporting breast cancer cells in bone, but little is known about prostate cancer bone metastases and TGF-ß. Our study reveals that the TGFBR1 inhibitor SD208 effectively reduces prostate cancer bone metastases. TGF-ß upregulates in prostate cancer cells a set of genes associated with cancer aggressiveness and bone metastases, and the most upregulated gene was PMEPA1. In patients, PMEPA1 expression decreased in metastatic prostate cancer and low Pmepa1 correlated with decreased metastasis-free survival. Only membrane-anchored isoforms of PMEPA1 interacted with R-SMADs and ubiquitin ligases, blocking TGF-ß signaling independently of the proteasome. Interrupting this negative feedback loop by PMEPA1 knockdown increased prometastatic gene expression and bone metastases in a mouse prostate cancer model.

Single-Limb Irradiation Induces Local and Systemic Bone Loss in a Murine Model.

Increased fracture risk is commonly reported in cancer patients receiving radiotherapy, particularly at sites within the field of treatment. The direct and systemic effects of ionizing radiation on bone at a therapeutic dose are not well-characterized in clinically relevant animal models. Using 20-week-old male C57Bl/6 mice, effects of irradiation (right hindlimb; 2 Gy) on bone volume and microarchitecture were evaluated prospectively by microcomputed tomography and histomorphometry and compared to contralateral-shielded bone (left hindlimb) and non-irradiated control bone. One week postirradiation, trabecular bone volume declined in irradiated tibias (-22%; p < 0.0001) and femurs (-14%; p = 0.0586) and microarchitectural parameters were compromised. Trabecular bone volume declined in contralateral tibias (-17%; p = 0.003), and no loss was detected at the femur. Osteoclast number, apoptotic osteocyte number, and marrow adiposity were increased in irradiated bone relative to contralateral and non-irradiated bone, whereas osteoblast number was unchanged. Despite no change in osteoblast number 1 week postirradiation, dynamic bone formation indices revealed a reduction in mineralized bone surface and a concomitant increase in unmineralized osteoid surface area in irradiated bone relative to contralateral and non-irradiated control bone. Further, dose-dependent and time-dependent calvarial culture and in vitro assays confirmed that calvarial osteoblasts and osteoblast-like MC3T3 cells were relatively radioresistant, whereas calvarial osteocyte and osteocyte-like MLO-Y4 cell apoptosis was induced as early as 48 hours postirradiation (4 Gy). In osteoclastogenesis assays, radiation exposure (8 Gy) stimulated murine macrophage RAW264.7 cell differentiation, and coculture of irradiated RAW264.7 cells with MLO-Y4 or murine bone marrow cells enhanced this effect. These studies highlight the multifaceted nature of radiation-induced bone loss by demonstrating direct and systemic effects on bone and its many cell types using clinically relevant doses; they have important implications for bone health in patients treated with radiation therapy.

MicroRNA 196B regulates FAS-mediated apoptosis in colorectal cancer cells.

Using miRNA microarray analysis, we identified 31 miRNAs that were significantly up-regulated or down-regulated in colon cancer tissues. We chose MIR196B, which was specifically up-regulated in colon cancer, for further study. We identified 18 putative MIR196B target genes by comparing between the mRNAs down-regulated in MIR196B-overexpressed cells and the assumed MIR196B target genes predicted by public bioinformatics tools. The association between MIR196B and FAS was verified in this study. FAS expression was constitutively elevated in normal human colorectal tissues. However, its expression was often reduced in human colorectal cancer. The decrease in FAS expression could be responsible for the reduction of apoptosis in colorectal cancer cells. In colorectal cancer tissue, we showed that MIR196B up-regulation was mutually followed by down regulation of FAS expression. We also showed that MIR196B directly repressed FAS expression in colorectal cells. Furthermore, anti-MIR196B up-regulated FAS expression and increased apoptosis in colorectal cancer cell lines. Our results suggest that the up-regulation of MIR196B modulates apoptosis in colorectal cancer cells by partially repressing FAS expression and that anti-MIR196B could be a potential candidate as an anti-cancer drug in colorectal cancer therapy.

Imaging findings of desmoplastic fibroma rarely involving the clavicle: case report.

Desmoplastic fibroma of bone is a rare locally aggressive, but non-metastatic tumor. In this case report, we present a desmoplastic fibroma in an unusual location, the clavicle. Desmoplastic fibroma involving the clavicle is extremely rare, with only 2 reported cases before 1985. We report the imaging findings of a desmoplastic fibroma of the clavicle with a review of the relevant literature.

Depression in non-Korean women residing in South Korea following marriage to Korean men.

PURPOSE: The purpose of the study was to examine the roles of acculturative stress, life satisfaction, and language literacy in depression in non-Korean women residing in South Korea following marriage to Korean men. METHODS: A cross-sectional study was performed, using an anonymous, self-reporting questionnaire. A total of 173 women were selected using a proportional stratified random sampling method. The relation between acculturation, depression, language literacy, life satisfaction and socio-demographic variables and the predictors of depression among participants were analyzed. The analysis included descriptive statistics and hierarchical multiple regression. RESULTS: Of the participants, 9.2% had depression, which was almost twice the rate of depression found in the general Korean population. In hierarchical multiple regression analysis, acculturative stress (beta=-.325, P<.001) and life satisfaction (beta=-.282, P=.003) were significantly associated with the level of depression. This final model was statistically significant and life satisfaction, acculturative stress, language literacy accounted for 31.0% (adjusted R(2)) of the variance in the depression score (P<.001). CONCLUSIONS: Elevated acculturative stress and less life satisfaction were significantly associated with a higher level of depression in migrant wives in Korea. Implications for practice and research are discussed.

The influence of psychosomatic symptoms, physical and sexual abuse, and coping strategies on delinquent behavior among Korean adolescents.

PURPOSE: This cross-sectional study was undertaken to examine the contributing factors related to juvenile delinquency, as well as to identify the effect of psychosomatic symptoms, physical abuse, sexual abuse, and coping strategies on delinquent behavior among Korean adolescents. METHODS: To investigate the research problem, 2,146 adolescents, including 1,350 student adolescents and 796 delinquent adolescents, were assessed using a cross-sectional descriptive design study via anonymous, self-reporting questionnaires. Almost all research variables were measured using the Mental Health Questionnaire for Korean Adolescents. RESULTS: Our results revealed that delinquent adolescents showed a greater incidence of psychosomatic symptoms, higher levels of physical and sexual abuse, and a higher level of less effective coping strategies compared with student adolescents. Our path analysis revealed that the likelihood of delinquent behavior among adolescents appeared to be influenced mainly by sexual abuse, Psychosomatic Symptoms I, and physical abuse, with these three variables having the highest total effect. CONCLUSIONS: This study confirms the relationships previously identified among stress, somatic complaints, and ineffective coping. In addition, we demonstrated that these relationships cover a wide spectrum, ranging from psychosomatic symptoms to behavioral problems. Further implications of the results and research limitation were discussed.