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1.
Ann Surg Treat Res ; 105(5): 297-309, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38023431

ABSTRACT

Purpose: Immune checkpoint inhibitors (ICIs) have been shown significant oncological improvements in several cancers. However, ICIs are still in their infancy in hepatocellular carcinoma (HCC). Programmed cell death-ligand 1 (PD-L1), tumor-infiltrating lymphocytes (TILs), and epithelial-mesenchymal transition (EMT) have been known as prognostic factors in HCC. Therefore, we have focused on identifying the molecular mechanisms between each marker to evaluate a predictive role. Methods: Formalin-fixed paraffin-embedded samples were obtained from 166 patients with HCC who underwent surgery. The expression of PD-L1 and TILs and EMT marker were evaluated by immunohistochemical analysis. Results: The multivariate analysis showed that TIL expression (hazard ratio [HR], 0.483; 95% confidence interval [CI], 0.269-0.866; P = 0.015) were independent prognostic factors for overall survival. The prognostic factors for disease-free survival were EMT marker expression (HR, 1.565; 95% CI, 1.019-2.403; P = 0.005). Patients with high expression of TILs had significantly better survival compared to patients with low expression (P = 0.023). Patients who were TIL+/EMT- showed a significantly better prognosis than those who were TIL-/EMT+ (P = 0.049). Conclusion: This study demonstrates that PD-L1 expression of TILs is closely associated with EMT marker expression in HCC. Clinical investigations using anti-PD-1/PD-L1 inhibitors in patients with EMT-associated PD-L1 upregulation are warranted.

2.
In Vivo ; 37(5): 2296-2305, 2023.
Article in English | MEDLINE | ID: mdl-37652526

ABSTRACT

BACKGROUND/AIM: Deubiquitinating enzyme 3 (DUB3) is a member of the ubiquitin-specific proteases family involved in regulating cell proliferation, invasion, and apoptosis. However, the biological role and clinicopathological significance of DUB3 expression have not been elucidated in non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: We evaluated the expression of DUB3 by immunohistochemistry using tissue microarrays and assessed the clinicopathologic significance of DUB3 expression levels in 187 patients with NSCLC, including its two major subtypes (93 cases of adenocarcinoma and 72 cases of squamous cell carcinoma). RESULTS: In adenocarcinoma, we observed that DUB3 expression had an effect on tumor size (p=0.030), vessel invasion (p=0.038), T stage (p=0.014), and tumor recurrence (p=0.002). Kaplan-Meier curves with log-rank test showed that high DUB3 expression was correlated with significantly more favorable clinical outcomes compared to those of the low expression group in adenocarcinoma (p=0.013). Multivariate analysis of disease-free survival also demonstrated that DUB3 expression is an independent prognostic factor in lung adenocarcinoma (p=0.017). Additionally, we identified the correlation between DUB3 and the expression of large tumor suppressor kinase 1 expression, a core protein of the Hippo pathway. CONCLUSION: DUB3 could function as a tumor suppressor by regulating the Hippo pathway in lung adenocarcinoma and can be considered a powerful predictive factor and therapeutic target.


Subject(s)
Adenocarcinoma of Lung , Adenocarcinoma , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Adenocarcinoma/metabolism , Adenocarcinoma of Lung/genetics , Biomarkers, Tumor/metabolism , Neoplasm Recurrence, Local , Prognosis , Protein Serine-Threonine Kinases/genetics
3.
Medicine (Baltimore) ; 102(22): e33785, 2023 Jun 02.
Article in English | MEDLINE | ID: mdl-37266617

ABSTRACT

RATIONALE: Breast augmentation is usually performed by inserting implants into the breasts. However, injectable fillers are sometimes used for the convenience of both patients and surgeons. If foreign substances, such as biomaterials, are injected into the body, complications such as inflammation, granuloma, and tissue necrosis can occur owing to foreign body reactions. PATIENT CONCERNS: A 39-year-old female patient visited our hospital complaining of tenderness, redness, and swelling in both breasts. The patient had undergone bilateral breast augmentation using implants 4 years prior to current consult. DIAGNOSES: On magnetic resonance imaging (MRI), cystic lesions and fluid collections were observed, with findings suggesting implant rupture; hence, surgery was planned to remove both implants. INTERVENTIONS: Intraoperatively, the implant was malpositioned in the upper lateral portion without rupture. Capsular contracture findings were also not prominent. A large amount of inflammatory granuloma was observed and removed in the prepectoral plane, and the implants were immediately inserted into a new subpectoral plane. OUTCOMES: The volume of the new implant was 175 mL, which was smaller than the previous one, as per the patient preference. Cytology of the fluid from the previous implant pocket showed no evidence of malignancy, and the granuloma was identified as inflammatory tissue caused by a foreign body reaction on biopsy. The excessive protrusion of both breasts was corrected after surgery, and the patient was satisfied with the aesthetic outcomes without any complications up to 3 months after surgery. LESSONS: The use of injectable fillers for breast augmentation carries the risk of misdiagnosis, and, therefore, surgeons should always exercise caution.


Subject(s)
Breast Implantation , Breast Implants , Mammaplasty , Female , Humans , Adult , Breast Implants/adverse effects , Breast Implantation/methods , Breast/surgery , Mammaplasty/methods , Reoperation/methods , Foreign-Body Reaction/diagnosis , Foreign-Body Reaction/etiology , Foreign-Body Reaction/surgery , Retrospective Studies
4.
Life (Basel) ; 13(3)2023 Mar 13.
Article in English | MEDLINE | ID: mdl-36983926

ABSTRACT

2-deoxy-2-[18F]fluoro-D-glucose (FDG) uptake of the reticuloendothelial system, including the bone marrow (BM) and spleen, on positron emission tomography/computed tomography (PET/CT) has been shown to be a significant prognostic factor in diverse malignancies. However, the relationship between FDG uptake of the BM and spleen and histopathological findings, including the tumor immune microenvironment, has not been fully evaluated. This study aimed to investigate the relationship of FDG uptake in the BM and spleen with histopathological findings and recurrence-free survival (RFS) in patients with gastric cancer. Seventy patients with gastric cancer who underwent pre-operative FDG PET/CT and subsequent curative surgery were retrospectively enrolled. On image analysis, the BM-to-liver uptake ratio (BLR) and spleen-to-liver uptake ratio (SLR) were measured from PET/CT images, and on immunohistochemical analysis, the densities of immune cell infiltration in the tumor tissue were graded. The BLR and SLR showed significant positive correlations with the grades of CD163 cell and CD8 cell infiltration in the tumor tissue, respectively (p < 0.05). In multivariate survival analysis, both BLR and SLR were significant predictors of RFS (p < 0.05). FDG uptake in the BM and spleen might be potential imaging biomarkers for evaluating tumor immune microenvironment conditions and predicting RFS in patients with gastric cancer.

5.
Int J Mol Sci ; 23(19)2022 Oct 09.
Article in English | MEDLINE | ID: mdl-36233285

ABSTRACT

This study aimed to assess the relationship between the histopathological and textural features of perigastric adipose tissue (AT) on 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) and to evaluate the prognostic significance of perigastric AT textural features in predicting recurrence-free survival (RFS) in patients with gastric cancer. Sixty-nine patients with gastric cancer who underwent staging [18F]FDG PET/CT and subsequent curative surgery were retrospectively reviewed. Textural features of perigastric AT were extracted from PET images. On histopathological analysis, CD4, CD8, and CD163 cell infiltration and matrix metalloproteinase-11 and interleukin-6 (IL-6) expression in perigastric AT were graded. The degree of CD163 cell infiltration in perigastric AT was significantly correlated with the mean standardized uptake value (SUV), SUV histogram entropy, grey-level co-occurrence matrix (GLCM) energy, and GLCM entropy of perigastric AT. The degree of IL-6 expression in the perigastric AT was significantly correlated with the mean and median SUVs of perigastric AT. In multivariate survival analysis, GLCM entropy, GLCM dissimilarity, and GLCM homogeneity of perigastric AT were significant predictors of RFS. The textural features of perigastric AT on [18F]FDG PET/CT significantly correlated with inflammatory response in perigastric AT and were significant prognostic factors for predicting RFS in patients with gastric cancer.


Subject(s)
Fluorodeoxyglucose F18 , Stomach Neoplasms , Adipose Tissue/diagnostic imaging , Adipose Tissue/metabolism , Fluorodeoxyglucose F18/metabolism , Glucose , Humans , Interleukin-6 , Matrix Metalloproteinases , Positron Emission Tomography Computed Tomography , Radiopharmaceuticals , Retrospective Studies
6.
Cancers (Basel) ; 14(16)2022 Aug 15.
Article in English | MEDLINE | ID: mdl-36010928

ABSTRACT

The relationship between 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) textural features and histopathological findings in gastric cancer has not been fully evaluated. We investigated the relationship between the textural features of primary tumors on FDG PET/CT with histopathological findings and recurrence-free survival (RFS) in patients with advanced gastric cancer (AGC). Fifty-six patients with AGC who underwent FDG PET/CT for staging work-ups were retrospectively enrolled. Conventional parameters and the first- and second-order textural features of AGC were extracted using PET textural analysis. Upon histopathological analysis, along with histopathological classification and staging, the degree of CD4, CD8, and CD163 cell infiltrations and expressions of interleukin-6 and matrix-metalloproteinase-11 (MMP-11) in the primary tumor were assessed. The histopathological classification, Lauren classification, lymph node metastasis, CD8 T lymphocyte and CD163 macrophage infiltrations, and MMP-11 expression were significantly associated with the textural features of AGC. The multivariate survival analysis showed that increased FDG uptake and intra-tumoral metabolic heterogeneity were significantly associated with an increased risk of recurrence after curative surgery. Textural features of AGC on FDG PET/CT showed significant correlations with the inflammatory response in the tumor microenvironment and histopathological features of AGC, and they showed significant prognostic values for predicting RFS.

7.
Eur J Radiol ; 145: 110047, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34801879

ABSTRACT

PURPOSE: This study investigated the relationship of imaging features of primary tumor and peritumoral VAT on PET/CT with histopathological findings of peritumoral VAT and recurrence-free survival (RFS) in patients with colorectal cancer. METHODS: We retrospectively reviewed 133 patients diagnosed with colorectal cancer who underwent staging FDG PET/CT and received curative surgery. Histogram-based imaging features of primary tumor and peritumoral VAT were extracted from PET/CT images. Based on histopathological analysis of peritumoral VAT, the degree of CD4, CD8, and CD163 cell infiltration and the expression of matrix metalloproteinase-11 and interleukin 6 (IL-6) were graded. Differences in imaging parameters based on the histopathological results and the relationships between imaging features and RFS were assessed. RESULTS: Mean CT-attenuation and SUV of peritumoral VAT showed significant positive correlation with CD163 cell infiltration and IL-6 expression of peritumoral VAT. Univariable survival analysis revealed significant correlation between RFS and the mean CT-attenuation, mean SUV, and first-order SUV entropy of peritumoral VAT (p < 0.05). Multivariable analysis indicated that mean SUV and SUV entropy of peritumoral VAT remained significant predictors of RFS after adjustment for age, sex, and T stage (p < 0.05). CONCLUSION: FDG uptake of peritumoral VAT was significantly associated with inflammatory response in peritumoral VAT and was an independent predictor of RFS in colorectal cancer patients.


Subject(s)
Colorectal Neoplasms , Positron Emission Tomography Computed Tomography , Adipose Tissue , Colorectal Neoplasms/diagnostic imaging , Fluorodeoxyglucose F18 , Humans , Positron-Emission Tomography , Prognosis , Radiopharmaceuticals , Retrospective Studies
8.
Int J Clin Exp Pathol ; 13(9): 2401-2406, 2020.
Article in English | MEDLINE | ID: mdl-33042351

ABSTRACT

Ovarian yolk sac tumors are common germ cell tumors usually arising in young women. Yolk sac tumors in elderly women are infrequently encountered and most of them are combined with other epithelial tumor components including endometrioid carcinoma or serous carcinoma. Here, we report an extremely rare case of a yolk sac tumor with mucinous tumor and large cell neuroendocrine carcinoma components in a postmenopausal woman, which is the third yolk sac tumor case with a neuroendocrine tumor element in an elderly woman. An 82-year-old female visited our hospital due to abdominal distention. Abdominal computed tomography (CT) demonstrated a solid and cystic mass, measuring about 9.0 cm in the largest diameter. A total hysterectomy with bilateral salpingo-oophorectomy and excisional biopsy of the peritoneal metastatic lesions was performed. Histologic evaluation revealed a malignant ovarian tumor composed of a variety of tumor components, including a yolk sac tumor, a mucinous tumor with multifocal mucinous carcinomatous areas, and a large-cell neuroendocrine carcinoma. After surgery, the patient refused further treatment and the disease recurred in the pelvic peritoneum and a left supraclavicular lymph node nine months later.

9.
Pathol Res Pract ; 216(11): 153188, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32919305

ABSTRACT

The immunohistochemical analysis of PD-L1 expression is still important in cancer immunotherapy. PD-L1 expression is affected by various tumor microenvironmental factors including tumor infiltrating lymphocytes (TILs) and DNA methylation biomarkers. Given the complex communication between tumor cells and immune cells, we analyzed the expression of PD-L1 and TET1 with TILs in human NSCLC and the correlation with various clinicopathological characteristics and patient prognosis. A total of 96 cases of NSCLC were enrolled in this study. Using tissue microarray, we performed immunohistochemical staining to analyze PD-L1 and TET1 expression. Image-Pro Plus was used as an automated imaging analysis software program to analyze the density of CD3+, CD4+ and CD8 + TILs. PD-L1 expression was positively correlated with the density of CD3+, CD4+ and CD8 + TILs (p = 0.038, p = 0.020, and p = 0.009, respectively); however, no significant relationship existed between TET1 expression and any TILs. The survival analysis revealed that a high PD-L1 expression was associated with favorable prognosis for OS (p = 0.049) and DFS (p = 0.029) in advanced-stage II-IV patients, but not in early stage I. Density of CD8+ TILs was an independent and favorable prognostic factor for DFS (p = 0.008) and OS (p = 0.002) in early-stage I patients. However, high TET-1 expression was associated with poor prognosis for OS (p = 0.029) in total NSCLC patients. These findings suggest the correlation and favorable prognostic impact of PD-L1 and TILs in NSCLC. In addition, DNA demethylase TET1 has oncogenic effects, showing association with poor prognosis.


Subject(s)
B7-H1 Antigen/metabolism , Carcinoma, Non-Small-Cell Lung/metabolism , Lung Neoplasms/metabolism , Lymphocytes, Tumor-Infiltrating/pathology , Mixed Function Oxygenases/metabolism , Proto-Oncogene Proteins/metabolism , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/metabolism , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Disease-Free Survival , Female , Humans , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Lymphocytes, Tumor-Infiltrating/metabolism , Male , Middle Aged , Prognosis , Survival Rate
10.
Pathol Res Pract ; 216(11): 153156, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32823232

ABSTRACT

Adenine-thymine-rich inactive domain-containing protein 1A (ARID1A) is a large subunit of the switch-sucrose nonfermenting (SWI-SNF) complex. ARID1A is considered to be a tumor suppressor in various cancers. We investigated the clinicopathological significance including prognosis of ARID1A expression in non-small cell lung cancer (NSCLC). ARID1A expression was studied by tissue microarray immunohistochemical analysis of 171 surgically resected NSCLC specimens including adenocarcinoma (ADC) and squamous cell carcinoma (SCC) on tissue microarray. Semiquantitative immunohistochemical score was obtained by multiplying the intensity and percentage scores. The overall score was further simplified by dichotomizing into either negative (score < 4) or positive (score ≥ 4) for each patient. The ARID1A-negative group revealed significantly higher correlations with male sex (p = 0.020), larger tumor size (p = 0.007), SCC than with ADC (p = 0.023) and smoking (p = 0.001). Univariate survival analysis showed that the ARID1A-negative group had a significantly shorter cancer specific survival than the ARID1A-positive group (p = 0.018). Multivariate survival analysis showed that ARID1A negativity (p = 0.022) were independent prognostic factors related with shorter cancer specific survival for NSCLC. In conclusion, Loss of ARID1A expression is a potential molecular marker to predictive of poor prognosis of NSCLC.


Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , DNA-Binding Proteins/metabolism , Lung Neoplasms/pathology , Transcription Factors/metabolism , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/metabolism , Female , Humans , Lung Neoplasms/metabolism , Male , Middle Aged , Prognosis , Retrospective Studies , Survival Analysis
11.
J Hepatobiliary Pancreat Sci ; 27(11): 839-850, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32351049

ABSTRACT

BACKGROUND/PURPOSE: The aim of the present study was to investigate the relationship between hepatobiliary scintigraphy findings and histopathological results in patients with recurrent biliary colic. METHODS: We retrospectively enrolled 107 patients who underwent hepatobiliary scintigraphy for recurrent biliary colic and subsequent cholecystectomy. According to the hepatobiliary scintigraphy findings, patients were categorized into a nonvisualization of gallbladder activity (nonvisualized GB) group, low gallbladder ejection fraction (GBEF) group, and normal GBEF group. Differences in histopathologic factors between the three groups were evaluated and multivariate logistic regression analyses were performed to identify histopathological predictors for hepatobiliary scintigraphy findings. RESULTS: The nonvisualized group had a higher frequency of patients with empyema and severe infiltration by neutrophils, lymphoplasma cells, and eosinophils. The low GBEF group had a higher muscle-to-total wall thickness ratio and muscle-to-fibrosis thickness ratio of the gallbladder wall than those in the normal GBEF group. On multivariate logistic regression analyses, severe degrees of lymphoplasma cell infiltration and eosinophil infiltration were independent predictors for nonvisualization of gallbladder activity, and a higher muscle-to-fibrosis thickness ratio was an independent predictor for low GBEF. CONCLUSIONS: In patients with recurrent biliary colic, nonvisualization of gallbladder activity on hepatobiliary scintigraphy was related to the degree of inflammation in the gallbladder, while low GBEF was related to muscular hypertrophy of the gallbladder.


Subject(s)
Colic , Gallbladder Diseases , Colic/diagnostic imaging , Gallbladder/diagnostic imaging , Gallbladder Diseases/diagnostic imaging , Humans , Radionuclide Imaging , Retrospective Studies
12.
J Craniofac Surg ; 31(1): 269-270, 2020.
Article in English | MEDLINE | ID: mdl-31764556

ABSTRACT

The facelift is one of the most popular cosmetic surgery methods of antiaging. There are many complications in facelift, but infections rarely occur relatively. The authors would like to introduce a patient who developed infection after a facelift procedure. The cause of the infection was preauricular sinus, one of the congenital anomalies. The patient was treated with complete excision of sinus tract and the patient was treated without any further complications. Based on this clinical report, surgeons performing cosmetic surgery need to be interested in rare congenital lesions such as preauricular sinus.


Subject(s)
Craniofacial Abnormalities/complications , Fistula/etiology , Infections/etiology , Postoperative Complications , Rhytidoplasty/adverse effects , Female , Fistula/diagnostic imaging , Fistula/pathology , Humans , Infections/diagnostic imaging , Infections/pathology , Middle Aged , Postoperative Complications/diagnostic imaging , Postoperative Complications/pathology , Surgery, Plastic
13.
Pol J Pathol ; 70(3): 189-197, 2019.
Article in English | MEDLINE | ID: mdl-31820862

ABSTRACT

Large tumor suppressor kinase 2 (LATS2) is a core component in the Hippo signaling pathway, and it functions as a tumor suppressor associated with tumor cell proliferation and apoptosis. The purpose of this study is to explore LATS2 expression and its clinicopathological significance in non-small cell lung cancer (NSCLC). We examined LATS2 protein expression by immunohistochemistry in 184 resected NSCLC specimens using tissue microarrays. Low LATS2 expression was significantly related to disease recurrence (p = 0.047). In survival analysis, the low LATS2 expression group showed a statistically poorer overall survival (OS) (p = 0.004) and disease-free survival (DFS) (p = 0.014) than the high expression group. In multivariate analysis, downregulated LATS2 expression in NSCLC could be an independent prognostic factor of poor OS and DFS. Furthermore, we evaluated the prognostic significance of LATS2 expression in two major NSCLC subtypes, squamous cell carcinoma and adenocarcinoma. The low LATS2 expression group showed worse prognosis than the high LATS2 expression group (OS [p = 0.144] and DFS [p = 0.022] in squamous cell carcinoma and OS [p = 0.045] and DFS [p = 0.271] in adenocarcinoma). We demonstrated that downregulated LATS2 expression may predict aggressive biologic behavior and a worse prognosis in NSCLC and we also suggested the possibility of LATS2 as a therapeutic target in both squamous cell carcinoma and adenocarcinoma.


Subject(s)
Carcinoma, Non-Small-Cell Lung/diagnosis , Lung Neoplasms/diagnosis , Protein Serine-Threonine Kinases/metabolism , Tumor Suppressor Proteins/metabolism , Adenocarcinoma/diagnosis , Adenocarcinoma/metabolism , Biomarkers, Tumor/metabolism , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/metabolism , Humans , Lung Neoplasms/metabolism , Prognosis
14.
Medicine (Baltimore) ; 98(42): e17423, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31626099

ABSTRACT

RATIONALE: Smooth muscle tumors of the vulva are infrequent neoplasms with diverse histologic features and unclear biologic behavior. Herein, we report a very rare case of vulvar epithelioid leiomyoma and review of previous reported cases of these tumors. In addition, we have discussed the representative diagnostic criteria of vulvar smooth muscle tumors and prognostic significance of epithelioid morphology. PATIENT CONCERNS: We recently met a 45-year-old woman with complaint of painful vulvar mass. INTERVENTIONS: Excisional biopsy was performed. DIAGNOSES: Pathologic examination revealed a vulvar epithelioid leiomyoma with multinodular growth pattern. Mitotic activity was rare and cellular atypia was not identified. Based on histology and immunohistochemical staining results, the case was diagnosed as vulvar epithelioid leiomyoma. OUTCOMES: After mass excision, the patient was discharged with no complication and there was no evidence recurrence for 6 months. LESSONS: After reviewing previous papers and diagnostic criterion, we thought that vulvar smooth muscle tumors with predominant epithelioid morphology may be associated with unfavorable prognosis, Therefore, pathologists should examine the epithelioid component in vulvar smooth muscle tumors carefully.


Subject(s)
Leiomyoma, Epithelioid/pathology , Myxoma/pathology , Smooth Muscle Tumor/pathology , Vulvar Neoplasms/pathology , Female , Humans , Middle Aged , Vulva/pathology
15.
Pathol Res Pract ; 214(3): 335-342, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29487002

ABSTRACT

EGFR tyrosine kinase inhibitor (EGFR TKI) is approved as first-line treatment for advanced-stage EGFR mutant lung adenocarcinoma (LADC). Yes-associated protein 1 (YAP1), a main effector of the Hippo pathway, is associated with adverse prognosis and disruption of EGFR TKI modulation of non-small cell lung cancer. In this study, we demonstrated a prognostic role of YAP1 in EGFR mutant LADC and efficacy of EGFR TKI therapy. A total of 63 patients, including 41 with paired lung cancer specimens before and after EGFR TKI therapy and 22 with non-paired lung cancer specimens prior to EGFR TKI, were enrolled for examination. Expression of YAP1 protein was evaluated using immunohistochemistry. Fifteen paired cases (36.6%) with high nuclear YAP1 expression were detected in the pre-EGFR TKI LADC group and 21 paired cases (52.5%) after treatment with EGFR TKI. Nuclear YAP1 expression was significantly upregulated after EGFR TKI therapy (P = .002). Fifteen paired cases with high nuclear YAP1 expression before EGFR TKI LADCs showed poorer overall survival (OS) (P = .023) and progression-free survival (PFS) (P = .041). Among the 63 patients under study, those with high nuclear YAP1 expression before EGFR TKI showed shorter OS (P = .038) and PFS (P < .001). High nuclear YAP1 expression in cases with acquired EGFR exon 20 T790 M mutant LADCs showed poorer OS (P < .001). We demonstrated that YAP1 burden before clinical application of EGFR TKI plays a crucial role in prognosis of EGFR mutant LADC treated using EGFR TKI.


Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Adenocarcinoma/genetics , Adenocarcinoma/mortality , ErbB Receptors/genetics , Lung Neoplasms/genetics , Lung Neoplasms/mortality , Mutation/genetics , Phosphoproteins/genetics , Adenocarcinoma/pathology , Adenocarcinoma of Lung , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Disease-Free Survival , Drug Resistance, Neoplasm/drug effects , ErbB Receptors/metabolism , Female , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Male , Middle Aged , Protein Kinase Inhibitors/therapeutic use , Transcription Factors , YAP-Signaling Proteins
16.
Medicine (Baltimore) ; 97(3): e9703, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29505025

ABSTRACT

Lymph node metastasis plays a crucial role in predicting prognosis in advanced gastric cancer (AGC). In the present study, we formulated a fibrosis ratio (FR), defined as the number of metastatic lymph nodes with fibrosis divided by the total number of lymph nodes, and sought to determine whether it can be used to predict the prognosis of patients with AGC and improve on existing node staging. We retrospectively analyzed 161 patients who underwent curative resection for node-positive AGC between 2001 and 2010, evaluating the association between FR, lymph node ratio (LNR), and micrometastasis, and the relationship between FR and clinicopathologic findings, overall survival (OS) and disease-free survival (DFS). A high FR was significantly related to T stage (P < .001), N stage (P < .001), tumor stage (P < .001), lymphatic invasion (P < .001), and venous invasion (P = .007). FR was significantly correlated with an increased number of metastatic lymph nodes (P = .001, R = 0.869) and LNR (P = .001, R = 0.943), but not with total harvested lymph nodes. Patients with micrometastases had a lower FR, compared with those without micrometastases (P < .001). A survival analysis showed poor OS for patients in the entire cohort (P < .001); N1 (P = .002), N2 (P = .004), N3a (P = .010), and N3b (P = .003) stages; and groups with high LNR (P = .013) and low LNR (P = .001). DFS was also poor for the entire cohort (P < .001) and the N2 (P = .013), N3b (P = .002), high-LNR (P = .036), and low-LNR (P = .001) groups, but not the N1 or N3a group. Univariate and multivariate analyses revealed that high FR was an independent prognostic factor for OS (hazard ratio [HR], 2.780; CI, 1.655-4.670; P < .001) and DFS (HR, 2.051; CI, 1.199-3.508; P = .009) in AGC. Collectively, our findings indicate that high FR is associated with adverse clinicopathologic parameters in AGC, clearly establishing nodal fibrosis as a pathological finding with value in predicting poor prognosis of patients with AGC. Thus, combining current N stage and LNR diagnostics with FR could improve prognostic prediction in AGC.


Subject(s)
Lymph Nodes/pathology , Stomach Neoplasms/pathology , Female , Fibrosis , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Staging , Predictive Value of Tests , Prognosis , Retrospective Studies
17.
APMIS ; 125(11): 996-1006, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28885730

ABSTRACT

Angiomotin (AMOT) promotes angiogenesis and plays a role in neovascularization during tumorigenesis. Recently, the AMOT isoform, AMOT-p130, was shown to exert a regulatory effect on Yes-associated protein 1 (YAP1), a major downstream effector of the Hippo pathway. The specific roles of AMOT-p130 and YAP1 in advanced gastric cancer (AGC) are yet to be established. In this study, a total of 166 patients with AGC were enrolled, and AMOT-p130 and YAP1 levels were analyzed by immunohistochemistry using tissue microarrays. Low AMOT-p130 together with high YAP1 expression (n = 30, 18.1%) was associated with high T stage (p = 0.042), high TNM stage (p = 0.025), and venous invasion (p = 0.048). A Kaplan-Meier survival analysis with log-rank test revealed a significant correlation with decreased AMOT-p130 coupled with high nuclear YAP1 expression with shorter overall survival (p = 0.0045) and disease-free survival (p = 0.0028). Furthermore, multivariate analyses showed that the low AMOT-p130/high YAP1 expression profile was an independent prognostic factor for disease-free survival (p = 0.008, HR = 1.874, CI, 1.177-2.986) and overall survival (p = 0.012, HR = 1.903, CI, 1.152-3.143). Our findings collectively demonstrate that low AMOT-p130 combined with high YAP1 expression is correlated with an unfavorable AGC prognosis.


Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Adenocarcinoma/diagnosis , Biomarkers, Tumor/genetics , Intercellular Signaling Peptides and Proteins/genetics , Membrane Proteins/genetics , Neovascularization, Pathologic/diagnosis , Phosphoproteins/genetics , Stomach Neoplasms/diagnosis , Adenocarcinoma/genetics , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Aged , Angiomotins , Female , Gene Expression , Humans , Kaplan-Meier Estimate , Male , Microfilament Proteins , Middle Aged , Multivariate Analysis , Neoplasm Staging , Neovascularization, Pathologic/genetics , Neovascularization, Pathologic/mortality , Neovascularization, Pathologic/pathology , Prognosis , Stomach Neoplasms/genetics , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Transcription Factors , YAP-Signaling Proteins
18.
Thorac Cancer ; 8(3): 278-282, 2017 05.
Article in English | MEDLINE | ID: mdl-28371214

ABSTRACT

Tracheal sarcomatoid carcinoma is an extremely infrequent neoplasm with unclear pathogenesis and clinical outcomes. To date, only two cases have been described in English literature. We report a case of a 37-year-old patient complaining of hemoptysis, dyspnea, and cough. An intraluminal polypoid mass in the trachea was found and ultimately diagnosed as tracheal sarcomatoid carcinoma in the cervical trachea with both carcinomatous and sarcomatoid morphology. The patient is alive without recurrence after segmental resection of the trachea. We also present a comparative analysis of our case with a prior tracheal sarcomatoid carcinoma case.


Subject(s)
Sarcoma/surgery , Trachea/surgery , Tracheal Neoplasms/surgery , Adult , Humans , Male , Neoplasm Recurrence, Local/pathology , Sarcoma/diagnosis , Sarcoma/pathology , Trachea/pathology , Tracheal Neoplasms/diagnosis , Tracheal Neoplasms/pathology
19.
J Breast Cancer ; 20(1): 45-53, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28382094

ABSTRACT

PURPOSE: Transducin-like enhancer of split 1 (TLE1) is a member of the TLE family of transcriptional co-repressors that control the transcription of a wide range of genes. We investigated the prognostic significance of TLE1 protein expression in breast cancers by using immunohistochemistry and explored the relationship of TLE1 with clinicopathological parameters. METHODS: Immunohistochemistry was performed on 456 cases of breast cancer tiled on tissue microarrays. The relationship between TLE1 expression in normal breast specimens and ductal carcinoma in situ (DCIS) was also analyzed. RESULTS: TLE1 was highly expressed in 57 of 456 (12.5%) carcinoma samples. TLE1 was more frequently expressed in DCIS and invasive breast cancers than in normal breast tissue (p=0.002). High expression of TLE1 significantly correlated with negative lymph node (LN) metastasis (p=0.007), high histologic grade (p<0.001), estrogen receptor negativity (p<0.001), progesterone receptor negativity (p<0.001), human epidermal growth factor receptor 2 (HER2) positivity (p<0.001), and high Ki-67 proliferation index (p<0.001). Based on intrinsic subtypes, high TLE1 expression was strongly associated with HER2+ and triple-negative breast cancers (TNBC) (p<0.001). Survival analysis demonstrated no significant association between TLE1 expression and disease-free survival (DFS) (p=0.167) or overall survival (OS) (p=0.286). In subgroup analyses, no correlation was found between TLE1 expression and DFS or OS according to LN status or intrinsic subtype. CONCLUSION: High TLE1 expression is significantly associated with the HER2+ and TNBC subtypes. This is the first study documenting immunohistochemical expression of TLE1 in invasive breast cancer and its association with clinicopathological parameters, prognosis, and intrinsic subtype.

20.
J Gastric Cancer ; 17(4): 363-373, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29302376

ABSTRACT

PURPOSE: The aims of this study were to evaluate the expression of the large tumor suppressor (LATS) genes LATS1 and LATS2 by immunohistochemical staining of gastric cancer, and to evaluate the clinicopathological significance of LATS expression and its correlation with overall survival (OS). MATERIALS AND METHODS: LATS1 and LATS2 expression in a tissue microarray was detected by immunohistochemistry, using 264 gastric cancer specimens surgically resected between July 2006 and December 2009. RESULTS: Low expression of LATS1 was significantly associated with more advanced American Joint Committee on Cancer (AJCC) stage (P=0.001) and T stage (P=0.032), lymph node (LN) metastasis (P=0.040), perineural invasion (P=0.042), poor histologic grade (P=0.007), and diffuse-type histology by the Lauren classification (P=0.033). Low expression of LATS2 was significantly correlated with older age (≥65, P=0.027), more advanced AJCC stage (P=0.001) and T stage (P=0.001), LN metastasis (P=0.004), perineural invasion (P=0.004), poor histologic grade (P<0.001), and diffuse-type histology by the Lauren classification (P<0.001). Kaplan-Meier survival analysis revealed significantly poor OS rates in the groups with low LATS1 (P=0.037) and LATS2 (P=0.037) expression. CONCLUSIONS: Expression of LATS1 or LATS2 is a significant marker for a good prognosis in patients with gastric cancer.

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