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Ocular PEComas are frequently melanotic and TFE3-translocated: report of two cases including the first description of PRCC-TFE3 fusion in PEComa Y. Gao, G. Chen, C. Chow, I. Io, E. W. N. Wong, W. M. S. Tsui, W. Y. Lam, K. F. To, J. K. C. Chan, Wah Cheuk Virchows Archiv.2021; 478(5): 1025. CrossRef
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Background Thymosin β4 is a multi-functional hormone-like polypeptide, being involved in cell migration, angiogenesis, and tumor metastasis. This study was undertaken to clarify the clinicopathologic implications of thymosin β4 expression in human colorectal cancers (CRCs).
Methods We investigated tissue sections from 143 patients with CRC by immunohistochemistry. In addition, we evaluated the expression patterns and the clinico-pathological significance of thymosin β4 expression in association with hypoxia inducible factor-1α (HIF-1α) expression in the CRC series.
Results High expression of thymosin β4 was significantly correlated with lymphovascular invasion, invasion depth, regional lymph node metastasis, distant metastasis, and TNM stage. Patients with high expression of thymosin β4 showed poor recurrence-free survival (p = .001) and poor overall survival (p = .005) on multivariate analysis. We also found that thymosin β4 and HIF-1α were overexpressed and that thymosin β4 expression increased in parallel with HIF-1α expression in CRC.
Conclusions A high expression level of thymosin β4 indicates poor clinical outcomes and may be a useful prognostic factor in CRC. Thymosin β4 is functionally related with HIF-1α and may be a potentially valuable biomarker and possible therapeutic target for CRC.
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Adipose-Derived Mesenchymal Stem Cells Enhance Ovarian Cancer Growth and Metastasis by Increasing Thymosin Beta 4X-Linked Expression Yijing Chu, Min You, Jingjing Zhang, Guoqiang Gao, Rendong Han, Wenqiang Luo, Tingting Liu, Jianxin Zuo, Fuling Wang Stem Cells International.2019; 2019: 1. CrossRef
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Background Cancer stem cells have been investigated as new targets for colorectal cancer (CRC) treatment. We recently reported that CD133+ colon cancer cells showed chemoresistance to 5-fluorouracil through increased survivin expression and proposed the survivin inhibitor YM155 as an effective therapy for colon cancer in an in vitro study. Here, we investigate the relationship between survivin and CD133 expression in surgically resected CRC to identify whether the results obtained in our in vitro study are applicable to clinical samples.
Methods We performed immunohistochemical staining for survivin and CD133 in surgically resected tissue from 187 stage II or III CRC patients. We also comparatively analyzed apoptosis according to survivin and CD133 expression using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling.
Results The results of the Mantel-Haenszel test established a linear association between nuclear survivin and CD133 expression (p = .018), although neither had prognostic significance, according to immunohistochemical expression level. No correlation was found between survivin expression and the following pathological parameters: invasion depth, lymph node metastasis, or histologic differentiation (p > .05). The mean apoptotic index in survivin+ and CD133+ tumors was higher than that in negative tumors: 5.116 ± 4.894 in survivin+ versus 4.103 ± 3.691 in survivin– (p = .044); 5.165 ± 4.961 in CD133+ versus 4.231 ± 3.812 in CD133– (p = .034).
Conclusions As observed in our in vitro study, survivin expression is significantly related to CD133 expression. Survivin may be considered as a new therapeutic target for chemoresistant CRC.
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Upregulation of EMR1 (ADGRE1) by Tumor-Associated Macrophages Promotes Colon Cancer Progression by Activating the JAK2/STAT1,3 Signaling Pathway in Tumor Cells Rokeya Akter, Rackhyun Park, Soo Kyung Lee, Eun ju Han, Kyu-Sang Park, Junsoo Park, Mee-Yon Cho International Journal of Molecular Sciences.2024; 25(8): 4388. CrossRef
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Obatoclax, a Pan-BCL-2 Inhibitor, Downregulates Survivin to Induce Apoptosis in Human Colorectal Carcinoma Cells Via Suppressing WNT/β-catenin Signaling Chi-Hung R. Or, Chiao-Wen Huang, Ching-Chin Chang, You-Chen Lai, Yi-Ju Chen, Chia-Che Chang International Journal of Molecular Sciences.2020; 21(5): 1773. CrossRef
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MUC1‐ and Survivin‐based DNA Vaccine Combining Immunoadjuvants CpG and interleukin‐2 in a Bicistronic Expression Plasmid Generates Specific Immune Responses and Antitumour Effects in a Murine Colorectal Carcinoma Model C. Liu, Y. Xie, B. Sun, F. Geng, F. Zhang, Q. Guo, H. Wu, B. Yu, J. Wu, X. Yu, W. Kong, H. Zhang Scandinavian Journal of Immunology.2018; 87(2): 63. CrossRef
Activated STAT3 may participate in tumor progression through increasing CD133/survivin expression in early stage of colon cancer Wanlu Li, Mi-Ra Lee, Taeyeong Kim, Young Wan Kim, Mee-Yon Cho Biochemical and Biophysical Research Communications.2018; 497(1): 354. CrossRef
MiRNA-142-3p increases radiosensitivity in human umbilical cord blood mononuclear cells by inhibiting the expression of CD133 Fang Yuan, Lu Liu, Yonghong Lei, Yi Hu Scientific Reports.2018;[Epub] CrossRef
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Background Mutations in the KRAS gene have been identified in approximately 50% of colorectal cancers (CRCs). KRAS mutations are well established biomarkers in anti–epidermal growth factor receptor therapy. Therefore, assessment of KRAS mutations is needed in CRC patients to ensure appropriate treatment.
Methods We compared the analytical performance of the cobas test to Sanger sequencing in 264 CRC cases. In addition, discordant specimens were evaluated by 454 pyrosequencing.
Results KRAS mutations for codons 12/13 were detected in 43.2% of cases (114/264) by Sanger sequencing. Of 257 evaluable specimens for comparison, KRAS mutations were detected in 112 cases (43.6%) by Sanger sequencing and 118 cases (45.9%) by the cobas test. Concordance between the cobas test and Sanger sequencing for each lot was 93.8% positive percent agreement (PPA) and 91.0% negative percent agreement (NPA) for codons 12/13. Results from the cobas test and Sanger sequencing were discordant for 20 cases (7.8%). Twenty discrepant cases were subsequently subjected to 454 pyrosequencing. After comprehensive analysis of the results from combined Sanger sequencing–454 pyrosequencing and the cobas test, PPA was 97.5% and NPA was 100%.
Conclusions The cobas test is an accurate and sensitive test for detecting KRAS-activating mutations and has analytical power equivalent to Sanger sequencing. Prescreening using the cobas test with subsequent application of Sanger sequencing is the best strategy for routine detection of KRAS mutations in CRC.
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Single-center study on clinicopathological and typical molecular pathologic features of metastatic brain tumor Su Hwa Kim, Young Suk Lee, Sung Hak Lee, Yeoun Eun Sung, Ahwon Lee, Jun Kang, Jae-Sung Park, Sin Soo Jeun, Youn Soo Lee Journal of Pathology and Translational Medicine.2023; 57(4): 217. CrossRef
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Background Aurora kinase A (AURKA), or STK15/BTAK, is a member of the serine/threonine kinase family and plays important roles in mitosis and chromosome stability. This study investigated the clinical significance of AURKA expression in colorectal cancer patients in Korea.
Methods AURKA protein expression was evaluated by immunohistochemistry in 151 patients with colorectal adenocarcinoma using tissue microarray blocks. We analyzed the relationship between clinicopathological characteristics and AURKA expression. In addition, the prognostic significance of various clinicopathological data for progression-free survival (PFS) was assessed. Also we evaluated copy number variations by array comparative genomic hybridization and AURKA gene amplification using fluorescence in situ hybridization in colorectal carcinoma tissues.
Results AURKA gene amplification was found more frequently in the 20q13.2–13.33 gain-positive group than the group with no significant gain on the AURKA-containing locus. AURKA protein expression was detected in 45% of the cases (68/151). Positive staining for AURKA was observed more often in male patients (p = .035) and distally located tumors (p = .021). PFS was shorter in patients with AURKA expression compared to those with low-level AURKA expression (p < .001). Univariate analysis revealed that AURKA expression (p = .001), age (p = .034), lymphatic invasion (p = .001), perineural invasion (p = .002), and TNM stage (p = .013) significantly affected PFS. In a multivariate analysis of PFS, a Cox proportional hazard model confirmed that AURKA expression was an independent and significant prognostic factor in colorectal adenocarcinoma (hazard ratio, 3.944; p < .001).
Conclusions AURKA could serve as an independent factor to predict a poor prognosis in Korean colorectal adenocarcinoma patients.
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Background Programmed death ligand 1 (PD-L1) in tumor cells is known to promote immune escape of cancer by interacting with programmed cell death 1 (PD-1) in tumor infiltrating immune cells. Immunotherapy targeting these molecules is emerging as a new strategy for the treatment of glioblastoma (GBM). Understanding the relationship between the PD-L1/PD-1 axis and prognosis in GBM patients may be helpful to predict the effects of immunotherapy.
Methods PD-L1 expression and PD-1–positive tumor infiltrating mononuclear cell (PD-1+tumor infiltrating mononuclear cell [TIMC]) density were evaluated using tissue microarray containing 54 GBM cases by immunohistochemical analysis; the associations with patient clinical outcomes were evaluated.
Results PD-L1 expression and high PD-1+TIMC density were observed in 31.5% and 50% of GBM cases, respectively. High expression of PD-L1 in tumor cells was an independent and significant predictive factor for worse overall survival (OS; hazard ratio, 4.958; p = .007) but was not a significant factor in disease-free survival (DFS). PD-1+TIMC density was not correlated with OS or DFS. When patients were classified based on PD-1 expression and PD-1+TIMC density, patients with PD-L1+/PD-1+TIMC low status had the shortest OS (13 months, p = .009) and DFS (7 months, p = .053).
Conclusions PD-L1 expression in GBM was an independent prognostic factor for poor OS. In addition, combined status of PD-L1 expression and PD-1+TIMC density also predicted patient outcomes, suggesting that the therapeutic role of the PD-1/PD-L1 axis should be considered in the context of GBM immunity.
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Background Immature teratoma (IT) is a tumor containing immature neuroectodermal tissue, primarily in the form of neuroepithelial tubules. However, the diagnosis of tumors containing only cellular neuroglial tissue (CNT) without distinct neuroepithelial tubules is often difficult, since the histological characteristics of immature neuroectodermal tissues remain unclear. Here, we examined the significance of CNT and tried to define immature neuroectodermal tissues by comparing the histological features of neuroglial tissues between mature teratoma (MT) and IT.
Methods The histological features of neuroglial tissue, including the cellularity, border between the neuroglial and adjacent tissues, cellular composition, mitotic index, Ki-67 proliferation rate, presence or absence of tissue necrosis, vascularity, and endothelial hyperplasia, were compared between 91 MT and 35 IT cases.
Results CNTs with a cellularity grade of ≥ 2 were observed in 96% of IT cases and 4% of MT cases (p < .001); however, CNT with a cellularity grade of 3 in MT cases was confined to the histologically distinct granular layer of mature cerebellar tissue. Moreover, CNT in IT exhibited significantly higher rates of Ki-67 proliferation, mitoses, and necrosis than those in MT (p < .001). Furthermore, an infiltrative border of neuroglial tissue and glomeruloid endothelial hyperplasia were significantly more frequent in IT cases than in MT cases (p < .001).
Conclusions Our results suggest that if CNT with a cellularity grade of ≥ 2 is not a component of cerebellar tissue, such cases should be diagnosed as IT containing immature neuroectodermal tissue, particularly if they exhibit an infiltrative border, mitoses, necrosis, and increased Ki-67 proliferation.
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Background We reviewed a series of 188 resected pulmonary mucinous adenocarcinomas (MAs) to clarify the prognostic significance of lepidic and non-lepidic patterns.
Methods Non-lepidic patterns were divided into bland, non-distorted acini with uncertain invasiveness (pattern 1), unequivocal invasion into stroma (pattern 2), or invasion into alveolar spaces (pattern 3).
Results The mean proportion of invasive patterns (patterns 2 and 3) was lowest in small (≤ 3 cm) tumors, and gradually increased in intermediate (> 3 cm and ≤ 7 cm) and large (> 7 cm) tumors (8.4%, 34.3%, and 50.1%, respectively). Adjusted T (aT) stage, as determined by the size of invasive patterns, was positively correlated with adverse histologic and clinical features including older age, male sex, and ever smokers. aTis tumors, which were exclusively composed of lepidic pattern (n = 9), or a mixture of lepidic and pattern 1 (n = 40) without any invasive patterns, showed 100% disease- free survival (DFS). The aT1mi tumors, with minimal (≤ 5 mm) invasive patterns (n = 63), showed a 95.2% 5-year DFS, with recurrences (n = 2) limited to tumors greater than 3 cm in total size (n = 23). Both T and aT stage were significantly associated with DFS; however, survival within the separate T-stage subgroups was stratified according to the aT stage, most notably in the intermediatestage subgroups. In multivariate analysis, the size of invasive patterns (p = .020), pleural invasion (p < .001), and vascular invasion (p = .048) were independent predictors of recurrence, whereas total size failed to achieve statistical significance (p = .121).
Conclusions This study provides a rationale for histologic risk stratification in pulmonary MA based on the extent of invasive growth patterns with refined criteria for invasion.
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Background Pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) has been associated with favorable clinical outcome in breast cancer patients. However, the possibility that the prognostic significance of pCR differs among various definitions has not been established. Methods: We retrospectively evaluated the pathologic response after NAC in 353 breast cancer patients and compared the prognoses after applying the following different definitions of pCR: ypT0/is, ypT0, ypT0/is ypN0, and ypT0 ypN0. Results: pCR was significantly associated with improved distant disease-free survival (DDFS) regardless of the definition (ypT0/is, p = .002; ypT0, p = .008; ypT0/is ypN0, p < .001; ypT0 ypN0, p = .003). Presence of tumor deposits of any size in the lymph nodes (LNs; ypN ≥ 0(i+)) was associated with worse DDFS (ypT0 ypN0 vs ypT0 ypN ≥ 0(i+), p = .036 and ypT0/is ypN0 vs ypT0/is ypN ≥ 0(i+), p = .015), and presence of isolated tumor cells was associated with decreased overall survival (OS; ypT0/is ypN0 vs ypT0/is ypN0(i+), p = .013). Residual ductal carcinoma in situ regardless of LN status showed no significant difference in DDFS or OS (DDFS: ypT0 vs ypTis, p = .373 and ypT0 ypN0 vs ypTis ypN0, p = .462; OS: ypT0 vs ypTis, p = .441 and ypT0 ypN0 vs ypTis ypN0, p = .758). In subsequent analysis using ypT0/is ypN0, pCR was associated with improved DDFS and OS in triple-negative tumors (p < .001 and p = .003, respectively). Conclusions: Based on our study results, the prognosis and rate of pCR differ according to the definition of pCR and ypT0/is ypN0 might be considered a more preferable definition of pCR.
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Background Liver transplantation (LT) is the treatment of choice for hepatocellular carcinoma (HCC). The aim of this study was to investigate the recurrence rate of HCC after LT and prognostic factors for recurrence by comparing LT with non-transplanted resection. Methods: The participants were 338 patients who underwent LT between 1996 and 2012 at Seoul National University Hospital (LT group) and 520 HCC patients who underwent partial hepatectomy between 1995 and 2006 (control group, non-LT group). Results: In the LT group, 68 of 338 patients (19.8%) showed relapse, and the recurrence rate was lower than that in the non-LT group (64.9%, 357/520, p < .001). Stratification analysis by American Joint Committee on Cancer (AJCC) stage showed that the stage I-II LT group had a lower recurrence rate than the non-LT group. Univariate comparative analysis demonstrated that multiplicity of tumor, tumor size, gross type, Edmondson- Steiner (ES) nuclear grade, extent of tumor, angioinvasion, AJCC stage, Milan criteria, University of California at San Francisco criteria on explant pathology (all p < .001), positive expression of cytokeratin 19 (p = .002), and preoperative α-fetoprotein (AFP) (p < .001) were predictors of tumor recurrence. In multivariate analysis, LT, preoperative AFP, multiplicity of tumor, extent of tumor, size of tumor, and ES nuclear grade were independent prognostic factors. Conclusions: LT might have a protective effect against the late recurrence of stage I-II HCC compared to non-LT, and the prognostic factors for recurrence were similar to previously well-known prognostic factors for HCC.
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Angioleiomyoma is a rare disease that is histologically characterized by smooth muscle cells arranged around vascular spaces. Although angioleiomyomas occur rarely in the head and neck region, they can cause various symptoms according the site involved. Here, we present a 44-yearold male patient with a 15-year history of asthma, who presented with recent onset of chest discomfort, globus sensation and throat pain. Medication was not effective in relieving his symptoms, and further evaluation revealed a polypoid ovoid mass, almost obstructing the airway at the border of the larynx and upper trachea on chest computed tomography. The mass was completely resected via a rigid bronchoscopy procedure. Histopathologic examination revealed that the excised mass was angioleiomyoma, which was immunohistochemically positive for smooth muscle actin and negative for desmin.
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