PWWP2B promotes DNA end resection and homologous recombination.

Genome instability is one of the leading causes of gastric cancers. However, the mutational landscape of driver genes in gastric cancer is poorly understood. Here, we investigate somatic mutations in 25 Korean gastric adenocarcinoma patients using whole-exome sequencing and show that PWWP2B is one of the most frequently mutated genes. PWWP2B mutation correlates with lower cancer patient survival. We find that PWWP2B has a role in DNA double-strand break repair. As a nuclear protein, PWWP2B moves to sites of DNA damage through its interaction with UHRF1. Depletion of PWWP2B enhances cellular sensitivity to ionizing radiation (IR) and impairs IR-induced foci formation of RAD51. PWWP2B interacts with MRE11 and participates in homologous recombination via promoting DNA end-resection. Taken together, our data show that PWWP2B facilitates the recruitment of DNA repair machinery to sites of DNA damage and promotes HR-mediated DNA double-strand break repair. Impaired PWWP2B function might thus cause genome instability and promote gastric cancer development.

TissueGene-C induces long-term analgesic effects through regulation of pain mediators and neuronal sensitization in a rat monoiodoacetate-induced model of osteoarthritis pain.

OBJECTIVE: TissueGene-C (TG-C), a combination of human allogeneic chondrocytes and irradiated GP2-293 cells engineered to overexpress transforming growth factor-ß1 (TGF-ß1), has been developed as a novel cell-based gene therapy and a candidate for disease modifying osteoarthritis drug (DMOAD). We aim to investigate analgesic mechanism of TG-C in a pre-clinical animal model with monoiodoacetate (MIA)-induced pain. DESIGN: We used a rat MIA model of osteoarthritis (OA) pain. We examined that TG-C can regulate pain by inhibiting the upregulation of various pain mediators in both knee joint tissue and dorsal root ganglia (DRG) (n = 112) and alleviating pain behavior (n = 41) and neuronal hyperexcitability in DRG (n = 60), afferent nerve fiber (n = 24), and spinal cord (n = 35). RESULTS: TG-C significantly alleviated pain-related behavior by restoring altered dynamic weight bearing and reduced mechanical threshold of the affected hindlimb. TG-C significantly suppressed the expression of nerve growth factor (NGF) and calcitonin gene-related peptide (CGRP) in inflamed joint tissue. TG-C significantly suppressed the upregulation of tropomyosin receptor kinase A (TrkA) and nerve injury/regeneration protein (GAP43) and activation of Iba1-positive microglial cells in DRG. TG-C significantly recovered neuronal hyperexcitability by restoring RMP and firing threshold and frequency of DRG neurons, attenuating firing rates of mechanosensitive C- or Aδ-nerve fiber innervating knee joint, and lowering increased miniature and evoked excitatory postsynaptic currents (mEPSCs and eEPSCs) in the spinal cord. CONCLUSION: Our results demonstrated that TG-C exerted potent analgesic effects in a rat MIA model of OA pain by inhibiting the upregulation of pain mediators and modulating neuronal sensitization.

A rare case of chordoma cutis.

Chordoma is a rare locally aggressive bone malignancy that originates from the notochord. It typically involves the sacrococcygeal area, spheno-occipital region of the skull, and spine. Cutaneous involvement of chordoma, termed as chordoma cutis, is uncommon and usually occurs via direct invasion or local recurrence. Distant metastasis to the skin is very rare. We report a case of chordoma cutis on the scalp, which lacked characteristic physaliferous cells but tested positive for brachyury, thus supporting the diagnosis of chordoma cutis. The patient, who presented with a solitary translucent nodule on the scalp, was previously diagnosed with chordoma on the vertebral column and skull 8 months prior. Microscopic examination showed a cord-like arrangement of plasmacytoid cells within a myxoid stroma. Physaliferous cells were not observed, and cytokeratin AE1/AE3 staining was negative; however, brachyury and epithelial membrane antigen staining was positive, leading to the diagnosis of chordoma cutis. Therefore, clinicians must include chordoma cutis in the differential diagnosis of translucent nodular lesions on the skin of patients formerly diagnosed with chordoma.

TissueGene-C promotes an anti-inflammatory micro-environment in a rat monoiodoacetate model of osteoarthritis via polarization of M2 macrophages leading to pain relief and structural improvement.

Osteoarthritis (OA) is the most common form of arthritis, characterized by cartilage destruction, pain and inflammation in the joints. Existing medications can provide relief from the symptoms, but their effects on the progression of the disease are limited. TissueGene-C (TG-C) is a novel cell and gene therapy for the treatment of OA, comprising a mixture of human allogeneic chondrocytes and irradiated cells engineered to overexpress transforming growth factor-ß1 (TGF-ß1). This study aims to investigate the efficacy and mechanism of action of TG-C in a rat model of OA. Using the monosodium-iodoacetate (MIA) model of OA, we examined whether TG-C could improve OA symptoms and cartilage structure in rats. Our results showed that TG-C provided pain relief and cartilage structural improvement in the MIA OA model over 56 days. In parallel with these long-term effects, cytokine profiles obtained on day 4 revealed increased expression of interleukin-10 (IL-10), an anti-inflammatory cytokine, in the synovial lavage fluid. Moreover, the increased levels of TGF-ß1 and IL-10 caused by TG-C induced the expression of arginase 1, a marker of M2 macrophages, and decreased the expression of CD86, a marker of M1 macrophages. These results suggest that TG-C exerts a beneficial effect on OA by inducing a M2 macrophage-dominant micro-environment. Cell therapy using TG-C may be a promising strategy for targeting the underlying pathogenic mechanisms of OA, reducing pain, improving function, and creating a pro-anabolic micro-environment. This environment supports cartilage structure regeneration and is worthy of further evaluation in future clinical trials.

Thyroid transcription factor-1 as a prognostic indicator for stage IV lung adenocarcinoma with and without EGFR-sensitizing mutations.

BACKGROUND: Thyroid transcription factor (TTF)-1 expression is a diagnostic marker and a good prognostic indicator for lung adenocarcinoma. However, its good prognostic ability might be due to epidermal growth factor receptor (EGFR)-sensitizing mutations as shown by the positive correlation between TTF-1 expression and EGFR mutations. We explored the prognostic impact of TTF-1 expression according to EGFR-sensitizing mutation status in lung adenocarcinoma patients. METHODS: We conducted a retrospective cohort study of patients with stage IV lung adenocarcinoma. Data were extracted from the lung cancer registry of Hallym University Medical Centers (three hospitals) in Korea between March 2006 and March 2016. RESULTS: Overall, 173 patients were included. EGFR-sensitizing mutations were detected in 84 (51.4%) patients. TTF-1 expression was positive in 139 (80.3%) patients; it was significantly correlated with EGFR-sensitizing mutations (p < 0.001). TTF-1-positive lung adenocarcinoma patients had longer overall survival (OS) than those who were TTF-1 negative (19.3 vs. 5.8 months, p < 0.001). In a Cox regression analysis, TTF-1 positivity, Stage IV M1a, good performance status, and EGFR-sensitizing mutations were independently associated with prolonged OS. In the subgroup of wild-type EGFR adenocarcinoma patients, TTF-1 positivity was also a good prognostic indicator for OS and progression-free survival (PFS) after first-line cytotoxic chemotherapy. CONCLUSIONS: TTF-1 expression was a good prognostic indicator for OS and PFS in stage IV lung adenocarcinoma patients with and without EGFR-sensitizing mutations.

Surface plasmon microscopy by spatial light switching for label-free imaging with enhanced resolution.

In this Letter, we describe spatially switched surface plasmon microscopy (ssSPM) based on two-channel momentum sampling. The performance evaluated with periodic nanowires in comparison with conventional SPM and bright-field microscopy shows that the resolution of ssSPM is enhanced by almost 15 times over conventional SPM. ssSPM provides an extremely simple way to attain diffraction limit in SPM and to go beyond for super-resolution in label-free microscopy techniques.

Phase II study of oxaliplatin, irinotecan and S-1 therapy in patients with advanced gastric cancer: the Korean Cancer Study Group ST14-11.

BACKGROUND: Doublet chemotherapy of platinum and 5-fluorouracil is a standard first-line treatment for patients with unresectable gastric cancer. Although the addition of taxane or irinotecan to this regimen has yielded promising efficacy, its use has been limited due to severe toxicities. To overcome this limitation, we evaluated the efficacy and safety of the combination of irinotecan, oxaliplatin, and S-1 (OIS) for the treatment of advanced gastric cancer. METHODS: Chemotherapy-naïve patients with pathologically proven advanced gastric adenocarcinoma were assessed for eligibility. Irinotecan (135 mg/m2) and oxaliplatin (65 mg/m2) were administered intravenously on day 1, and S-1 (80 mg/m2/day) was administered orally on days 1-7 of every 2-week cycle. RESULTS: Forty-four patients (median age 57 years) were enrolled and all but one patient had a good performance status (ECOG 0 or 1). A total of 529 cycles were administered, with a median of 9.5 (range 1-31) cycles per patient. The overall response rate was 61.4% (95% confidence interval [CI] 46.6-74.3). The median progression-free survival and overall survival were 10.8 months (95% CI 7.6-14.0) and 15.4 months (95% CI 12.6-18.2), respectively. Major toxicities included grade 3/4 neutropenia (38.6%), febrile neutropenia (13.6%), abdominal pain (9.1%), and diarrhea (9.1%). CONCLUSION: These data suggest that the OIS regimen is effective and relatively well tolerated in patients with advanced gastric cancer. Given that all the patients treated, but one, had a good performance status, these results must be confirmed in a patient population more representative of regular clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02527785.

5 nm Silver Nanoparticles Amplify Clinical Features of Atopic Dermatitis in Mice by Activating Mast Cells.

The triggering effect of silver nanoparticles (NPs) on the induction of allergic reactions is evaluated, by studying the activation of mast cells and the clinical features of atopic dermatitis in a mouse model. Granule release is induced in RBL-2H3 mast cells by 5 nm, but not 100 nm silver NPs. Increases in the levels of reactive oxygen species (hydrogen peroxide and mitochondrial superoxide) and intracellular Ca++ in mast cells are induced by 5 nm silver NPs. In a mouse model of atopic dermatitis induced by a mite allergen, the skin lesions are more severe and appear earlier in mice treated simultaneously with 5 nm silver NPs and allergen compared with mice treated with allergen alone or 100 nm silver NPs and allergen. The histological findings reveal that number of tryptase-positive mast cells and total IgE levels in the serum increase in mice treated with 5 nm silver NPs and allergen. The results in this study indicate that cotreatment with 5 nm silver NPs stimulates mast cell degranulation and induces earlier and more severe clinical alterations in allergy-prone individuals.

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.

Invasion Depth Measured in Millimeters is a Predictor of Survival in Patients with Distal Bile Duct Cancer: Decision Tree Approach.

BACKGROUND: AJCC staging system is unreliable for predicting survival in distal bile duct (DBD) cancer patients, due to inter-observer variation. Measured depth of invasion (DOI) is suggested to be more accurate to predict patients' clinical outcome in extra-hepatic cholangiocarcinomas, but its significance in DBD cancer and cutoff values are still debatable. This study aimed to identify the optimal cutoff value of DOI in relation to prognosis in DBD cancer patients. METHODS: Data of 179 patients with DBD adenocarcinoma treated in three institutions were investigated. Under microscopic review, DOI was measured. The relationships between the clinicopathological parameters and the groups based on DOI (≤3; 3-10; >10 mm) were evaluated, and the survival times of each group based on DOI and T classification were compared. RESULTS: Deeply invading tumors exhibited a greater tendency toward the infiltrative type, high histological grade, AJCC stage, and pancreatic, duodenal, lymphovascular and perineural invasion. The measured DOI was significantly correlated with worse relapse-free and overall survival (all p < 0.05). In multivariate analyses, the DOI remained as one of the prognostic factors (all p < 0.05), while T classification was not a significant prognostic factor. The new prognostic models (low, intermediate, and high risk) that applied DOI and nodal metastasis showed significant difference in recurrence and survival rate (all p < 0.05). CONCLUSIONS: On the basis of the proposed cutoff value, the DOI could be clear and meaningful, overcoming the vagueness of the T classification for predicting clinical outcomes in patients with DBD carcinoma.

A High Ki67/BCL2 Index Could Predict Lower Disease-Free and Overall Survival in Intestinal-Type Gastric Cancer.

BACKGROUND: The heterogeneity of gastric cancer makes the identification of potential prognostic indicators particularly important. The Ki67 and BCL2 proteins are known prognostic markers for different types of cancer. Ki67 is associated with cell proliferation, whereas BCL2 has antiproliferative roles. A combined marker based on these opposite functions might provide improved prognostic information in gastric cancer. METHOD: Ki67 and BCL2 expression was assessed in 276 gastric adenocarcinoma tissue microarrays. A Ki67/BCL2 index based on the relative expression of each protein was divided into low- and high-risk groups using receiver operating characteristic curves. RESULTS: A high Ki67/BCL2 index significantly correlated with advanced stage, recurrence, intestinal type, high histologic grade, and lymphatic and perineural invasion (all p < 0.05). Univariate and multivariate analyses revealed a significant relationship between disease-free or overall survival and the Ki67/BCL2 index in intestinal-type gastric cancer (all p < 0.05). CONCLUSIONS: A combined marker using Ki67 and BCL2 could be a useful indicator for predicting survival in patients with intestinal-type gastric cancer.

Macrophage Differentiation from Monocytes Is Influenced by the Lipid Oxidation Degree of Low Density Lipoprotein.

LDL plays an important role in atherosclerotic plaque formation and macrophage differentiation. However, there is no report regarding the oxidation degree of LDL and macrophage differentiation. Our study has shown that the differentiation into M1 or M2 macrophages is related to the lipid oxidation level of LDL. Based on the level of lipid peroxidation, LDL is classified into high-oxidized LDL (hi-oxLDL) and low-oxidized LDL (low-oxLDL). The differentiation profiles of macrophages were determined by surface receptor expression and cytokine secretion profiles. Low-oxLDL induced CD86 expression and production of TNF-α and IL-12p40 in THP-1 cells, indicating an M1 macrophage phenotype. Hi-oxLDL induced mannose receptor expression and production of IL-6 and monocyte chemoattractant protein-1, which mostly match the phenotype of M2 macrophages. Further supporting evidence for an M2 polarization by hi-oxLDL was the induction of LOX-1 in THP-1 cells treated with hi-oxLDL but not with low-oxLDL. Similar results were obtained in primary human monocytes. Therefore, our results strongly suggest that the oxidation degree of LDL influences the differentiation of monocytes into M1 or M2 macrophages and determines the inflammatory fate in early stages of atherosclerosis.

MET is a potential target for use in combination therapy with EGFR inhibition in triple-negative/basal-like breast cancer.

MET, a cell surface receptor for hepatocyte growth factor, is involved in the development of triple-negative/basal-like breast cancer (TNBC/BLBC). However, its utility as a therapeutic target in this subtype of breast cancer is poorly understood. To evaluate MET fully as a potential therapeutic target for TNBC/BLBC, we investigated the relationship between MET expression and clinical outcomes of patients with breast cancer and the functional effect of MET inhibition. Using automated immunohistochemistry (Ventana), we analyzed MET expression in 924 breast cancer patients with relevant clinicopathologic parameters. BLBC showed the strongest relationship with MET expression (57.5%, p < 0.001). High expression of MET in breast cancer resulted in poor overall survival (p = 0.001) and disease-free survival (DFS, p = 0.010). MET expression was relatively high in TNBC cell lines, and the silencing of MET via small interfering RNA reduced cell proliferation and migration. We observed reduced TNBC cell viability after treatment with the MET inhibitor PHA-665752. In the most drug-resistant cell line, MDA-MB-468, which showed elevated epidermal growth factor receptor (EGFR) expression, silencing of EGFR resulted in increased sensitivity to PHA-665752 treatment. We confirmed that PHA-665752 synergizes with the EGFR inhibitor erlotinib to decrease the viability of MDA-MB-468 cells. TNBC patients coexpressing MET and EGFR showed significantly worse DFS than that in patients expressing EGFR alone (p = 0.021). Our findings strongly suggest that MET may be a therapeutic target in TNBC and that the combined therapy targeting MET and EGFR may be beneficial for the treatment of TNBC/BLBC patients.

Mercury monitoring in the coastal areas of the Republic of Korea using the black-tailed gull egg as an indicator.

In the southeast and east coasts of the Republic of Korea, it is essential to monitor mercury accumulation in coastal organisms in view of the higher mercury distribution in sediments and human samples. However, mercury pollution monitoring in organisms, especially higher trophic-level organisms that can exhibit high mercury accumulation, is limited. Here, we examined the applicability of the eggs of the black-tailed gull (Larus crassirostris), which belongs to a high trophic level, for mercury monitoring in coastal areas. Breeding sites were selected in West, Southeast, and East Seas with different mercury concentrations in other matrices (sediment and biological samples of residents). The 5-year mean total mercury concentration in eggs collected during the breeding seasons from 2016 to 2020 was lower in Baengnyeongdo (705 ± 81 ng/g dry weight (dry), West Sea) than in Hongdo (1,207 ± 214 ng/g dry, Southeast Sea) and Ulleungdo (1,095 ± 95 ng/g dry, East Sea). The different patterns of mercury concentration in gull eggs among the breeding sites was consistent with those in the other matrices among the coastal areas. These results support the applicability of the black-tailed gull egg as an indicator for establishing a monitoring framework in the coastal areas of the Republic of Korea.

Comparison of Prophylactic Effects between Localized Biomimetic Minocycline and Systematic Amoxicillin on Implants Placed Immediately in Infected Sockets.

This study evaluated the prophylactic effect of localized biomimetic minocycline and systemic amoxicillin on immediate implant placement at infected extraction sites. Twelve mongrels with six implants each were randomly assigned to five groups: uninfected negative control (Group N); infected with oral complex bacteria (Group P); infected and treated with amoxicillin one hour before implant placement (Group A); infected and treated with minocycline during implant placement (Group B); and infected and treated with amoxicillin one hour before implant placement and with minocycline during implant placement (Group C). Radiographic bone level, gingival index (GI), probing depth (PD), papillary bleeding index (PBI), and removal torque (RT) were recorded. There was no significant difference between Groups A, B, and C for bone loss. Group A showed the highest RT, the lowest PBI, and significantly lower GI and PD values than Group P. Group B exhibited significantly higher RT value than Group N and significantly smaller PD value than Group P at 6 w postoperatively. Localized minocycline could improve implant success by reducing bone loss and increasing RT and systemic amoxicillin could maintain the stability of the peri-implant soft tissue. However, combined use of these two antibiotics did not augment the prophylactic effect.

Intra-sinus rigid fixation of a resorbable barrier membrane to repair a large perforation of the sinus membrane: a technical note.

A resorbable barrier membrane is commonly used for the repair of perforated sinus membranes during sinus lifting surgeries. However, repairing largescale perforations poses challenges for clinicians as the protection and isolation of graft material remain uncertain. With this technique, we aimed to prevent graft material loss and subsequent sinus-related complications using intra-sinus rigid fixation of the resorbable barrier membrane in cases with a large perforation of the sinus membrane.

Outcome of reclassification of World Health Organization (WHO) class III under International Society of Nephrology-Renal Pathology Society (ISN-RPS) classification: retrospective observational study.

The outcome of systemic lupus erythematosus (SLE) is largely influenced by the existence of lupus nephritis (LN), and its histologic classification guides the treatment and prognosis of SLE. International Society of Nephrology-Renal Pathology Society (ISN-RPS) announced a revised classification of LN in 2004. The present study investigated the differential outcome of World Health Organization (WHO) class III LN when reclassified according to ISN-RPS classification. Forty-three patients with biopsy-proven WHO class III LN at a single tertiary hospital were included in the study. Baseline characteristics at the time of renal biopsy and clinical data during follow-up were obtained from medical records. Renal response to treatment at one-year follow-up was analyzed in three ways; complete response (CR), partial response (PR), and no response (NR). Of 43 patients with previous WHO class III LN, 12 cases were reclassified into ISN-RPS class IV (9 cases of class IV-S and 3 cases of IV-G). Baseline characteristics at the time of renal biopsy were not different between the reclassified class IV and remaining class III LN group except activity index on renal histology, which was significantly elevated in the reclassified class IV group (4.90 vs. 6.75; P = 0.02). Significantly higher number of patients with remaining class III LN achieved CR to treatment than those with reclassified class IV LN at one-year follow-up since initial biopsy (CR: PR: NR; 16:7:7 vs. 3:1:8; P = 0.032). Our study suggests that the ISN-RPS classification is more advantageous in predicting renal outcome and guiding treatment when evaluating previously classified WHO class III LN.

Somatic Mutations of TP53 Identified by Targeted Next-Generation Sequencing Are Poor Prognostic Factors for Primary Operable Breast Cancer: A Single-Center Study.

Few studies have reported on the clinical utility of targeted next-generation sequencing (NGS) for breast cancer in Korea. We retrospectively reviewed the targeted NGS data of 219 patients with breast cancer who underwent surgical resection between August 2018 and April 2021. Here, we described the mutational profiles of breast cancer and examined their prognostic implications. The most frequently mutated gene was PIK3CA (n = 97/219, 44.3%), followed by TP53 (n = 79/219, 36.1%), AKT1 (n = 23/219, 10.5%), and GATA3 (n = 20/219, 9.1%). TP53 mutations were associated with aggressive histologic features. We followed up for 31 (range, 1-39) months and observed 11 (5.0%) recurrences: nine were TP53 mutant and two were TP53 wild-type. Multivariable analysis revealed that TP53 mutation was an independent prognostic factor for recurrence (p = 0.012). Although no drug is currently available for TP53 mutations, it is valuable to know the mutational status of TP53 for the precise management of breast cancer.

The current state of the osteoarthritis drug development pipeline: a comprehensive narrative review of the present challenges and future opportunities.

In this narrative review article, we critically assess the current state of the osteoarthritis (OA) drug development pipeline. We discuss the current state-of-the-art in relation to the development and evaluation of candidate disease-modifying OA drugs (DMOADs) and the limitations associated with the tools and methodologies that are used to assess outcomes in OA clinical trials. We focus on the definition of DMOADs, highlight the need for an updated definition in the form of a consensus statement from all the major stakeholders, including academia, industry, regulatory agencies, and patient organizations, and provide a summary of the results of recent clinical trials of novel DMOAD candidates. We propose that DMOADs should be more appropriately targeted and investigated according to the emerging clinical phenotypes and molecular endotypes of OA. Based on the findings from recent clinical trials, we propose key topics and directions for the development of future DMOADs.

PIK3CA Mutation as Potential Poor Prognostic Marker in Asian Female Breast Cancer Patients Who Received Adjuvant Chemotherapy.

Background: The prognostic relevance of the PIK3CA mutation together with PD-L1, c-Met, and mismatch repair deficiency (dMMR) have not been fully investigated in Asian women with breast cancer (BC) who have undergone postoperative adjuvant chemotherapy. Methods: We analyzed PIK3CA mutations via peptide nucleic acid (PNA)-mediated real-time PCR assay, PD-L1/c-Met expression via immunohistochemistry (IHC), and microsatellite instability (MSI) status using PCR and IHC, in 191 resected BCs from 2008 to 2011. The Cancer Genome Atlas (TCGA) dataset for the involvement of the PIK3CA mutation with PD-L1/c-Met/MMR was explored. Results: The PNA clamp-mediated assay was able to detect the PIK3CA mutation in 1% of the mutant population in the cell line validation. Using this method, the PIK3CA mutation was found in 78 (49.4%) of 158 samples. c-Met and PD-L1 positivity were identified in 31.4 and 21.8% of samples, respectively, which commonly correlated with high histologic grade and triple-negative subtype. MSI/dMMR was observed in 8.4% of patients, with inconsistency between MMR IHC and the MSI PCR. The PIK3CA mutation exhibited a poor prognostic association regarding recurrence-free survival (RFS) in both overall and triple-negative BCs. In subgroup analyses, the PIK3CA-mutated tumors showed poorer RFS than the PIK3CA-wildtype within the c-Met-positive, MSS, triple-negative, or age onset <50 years subgroups, which showed a similar trend of association in TCGA data. Conclusions: PIK3CA mutation together with c-Met or dMMR/MSI status might be relevant to poor prognosis in BC subsets, especially in Asian women.