Faculty Profiles - SHIMADA, Satoko

Predictive Performance of Radiomic Features Extracted from Breast MR Imaging in Postoperative Upgrading of Ductal Carcinoma in Situ to Invasive Carcinoma

Satake Hiroko, Kinoshita Fumie, Ishigaki Satoko, Kato Keita, Jo Yusuke, Shimada Satoko, Masuda Norikazu, Naganawa Shinji

Magnetic Resonance in Medical Sciences Vol. advpub ( 0 ) 2024.5

Language：English Publisher：Japanese Society for Magnetic Resonance in Medicine

Purpose: To investigate the predictive performance of radiomic features extracted from breast MRI for upgrade of ductal carcinoma in situ (DCIS) to invasive carcinoma.Methods: This retrospective study included 71 women with DCIS lesions diagnosed preoperatively by biopsy. All women underwent breast dynamic contrast-enhanced (DCE) MRI of the breast, which included pre-contrast and five post-contrast phases continuously with a time resolution of 60s. Lesion segmentation was performed manually, and 144 radiomic features of the lesions were extracted from T2-weighted images (T2WI), pre-contrast T1-weighted images (T1WI), and post-contrast 1st, 2nd, and 5th phase subtraction images on DCE-MRI. Qualitative features of mammography, ultrasound, and MRI were also assessed. Clinicopathological features were evaluated using medical records. The least absolute shrinkage and selection operator (LASSO) algorithm was applied for features selection and model building. The predictive performance of postoperative upgrade to invasive carcinoma was assessed using the area under the receiver operating characteristic curve.Results: Surgical specimens revealed 13 lesions (18.3%) that were upgraded to invasive carcinoma. Among clinicopathological and qualitative features, age was the only significant predictive variable. No significant radiomic features were observed on T2WI and post-contrast 2nd phase subtraction images on DCE-MRI. The area under the curves (AUCs) of the LASSO radiomics model integrated with age were 0.915 for pre-contrast T1WI, 0.862 for post-contrast 1st phase subtraction images, and 0.833 for post-contrast 5th phase subtraction images. The AUCs of the 200-times bootstrap internal validations were 0.885, 0.832, and 0.775.Conclusion: A radiomics approach using breast MRI may be a promising method for predicting the postoperative upgrade of DCIS. The present study showed that the radiomic features extracted from pre-contrast T1WI and post-contrast subtraction images in the very early phase of DCE-MRI were more predictable.

DOI： 10.2463/mrms.mp.2023-0168

Clinicopathological characteristics associated with the engraftment of patient lymphoma cells in NOG mice

CiNii Research

Sahashi, S; Shimada, K; Takagi, Y; Aoki, T; Kunou, S; Sakamoto, A; Murase, A; Furukawa, K; Kagaya, Y; Yamaga, Y; Takai, M; Tokuyama, K; Shimada, S; Nakamura, S; Kiyoi, H

INTERNATIONAL JOURNAL OF HEMATOLOGY Vol. 118 ( 2 ) page： 221 - 230 2023.8

Language：English Publisher：International Journal of Hematology

Patient-derived xenograft (PDX) mouse models are useful for deepening our understanding of the biology of malignant lymphoma; however, factors associated with the success of the PDX lymphoma model are largely unknown. We retrospectively analyzed the characteristics of 66 xenotransplantations from 65 patients. In all, 43 (65%) specimens were obtained from patients aged > 60 years, and 42 (64%) specimens were obtained at diagnosis. Specimens were obtained from patients with the following diseases: diffuse large B-cell lymphoma (n = 30), intravascular large B-cell lymphoma (n = 12), follicular lymphoma (n = 8), peripheral T-cell lymphoma (n = 7), mantle cell lymphoma (n = 2), and other (n = 7). The specimens were sourced mainly from bone marrow (n = 31, 47%) and extranodal tumors (n = 13, 20%). Engraftment was successful in 33/66 (50%) xenotransplantations. The median age of patients who provided successful specimens was significantly higher than that for unsuccessful specimens (p = 0.013). Specimens with a high proportion of tumor cells in the graft and those obtained from patients with relapsed/refractory disease showed higher tendencies toward successful engraftment. Taken together, these data suggest that tumor cells with a highly malignant potential might have a high likelihood of engraftment.

DOI： 10.1007/s12185-023-03604-z

Exosomes secreted from cancer-associated fibroblasts elicit anti-pyrimidine drug resistance through modulation of its transporter in malignant lymphoma

Two cases of solitary fibrous tumor/hemangiopericytoma with different clinical features according to the World Health Organization classification: case report and review of the literature.

Nishii T, Nagashima Y, Nishimura Y, Ito H, Oyama T, Matsuo M, Sakakibara A, Shimada S, Saito R

Journal of spine surgery (Hong Kong) Vol. 7 ( 4 ) page： 532 - 539 2021.12

Kunou Shunsuke, Shimada Kazuyuki, Takai Mika, Sakamoto Akihiko, Aoki Tomohiro, Hikita Tomoya, Kagaya Yusuke, Iwamoto Eisuke, Sanada Masashi, Shimada Satoko, Hayakawa Fumihiko, Oneyama Chitose, Kiyoi Hitoshi

ONCOGENE Vol. 40 ( 23 ) page： 3989 - 4003 2021.6

Language：Japanese Publisher：Oncogene

The tumor microenvironment is deeply involved in the process of tumor growth and development. In this study, we focused on cancer-associated fibroblasts (CAFs) and their derived exosomes on the lymphoma microenvironment to uncover their clinical significance. CAFs were established from primary lymphoma samples, and exosomes secreted from CAFs were obtained by standard procedures. We then investigated the roles of CAFs and their derived exosomes in the survival and drug resistance of lymphoma cells. CAFs supported the survival of lymphoma cells through increased glycolysis, and the extent differed among CAFs. Exosomes were identified as a major component of the extracellular vesicles from CAFs, and they also supported the survival of lymphoma cells. The suppression of RAB27B, which is involved in the secretion of exosomes, using a specific siRNA resulted in reduced exosome secretion and decreased survival of lymphoma cells. Moreover, anti-pyrimidine drug resistance was induced in the presence of exosomes through the suppression of the pyrimidine transporter, equilibrative nucleoside transporter 2 (ENT2), and the suppression of ENT2 was significant in in vivo experiments and clinical samples. RNA sequencing analysis of miRNAs in exosomes identified miR-4717-5p as one of the most abundant miRNAs in the exosome, which suppressed the expression of ENT2 and induced anti-pyrimidine drug resistance in vitro. Our results suggest that exosomes including miR-4717-5p secreted from CAFs play a pivotal role in the lymphoma microenvironment, indicating that they are a promising therapeutic target.

DOI： 10.1038/s41388-021-01829-y

The Positivity of Phosphorylated STAT3 Is a Novel Marker for Favorable Prognosis in Germinal Center B-Cell Type of Diffuse Large B-Cell Lymphoma

Morichika Kazuho, Karube Kennosuke, Sakihama Shugo, Watanabe Risa, Kawaki Mamoru, Nishi Yukiko, Nakachi Sawako, Okamoto Shiki, Takahara Taishi, Satou Akira, Shimada Satoko, Shimada Kazuyuki, Tsuzuki Toyonori, Fukushima Takuya, Morishima Satoko, Masuzaki Hiroaki

AMERICAN JOURNAL OF SURGICAL PATHOLOGY Vol. 45 ( 6 ) page： 832 - 840 2021.6

Language：Japanese Publisher：American Journal of Surgical Pathology

On the basis of immunohistochemistry, diffuse large B-cell lymphoma (DLBCL) is categorized as a germinal center B-cell (GCB) or non-GCB subtype. Recent integrated genomic analyses have highlighted the importance of the JAK-STAT3 pathway in the molecular pathogenesis of DLBCL. However, its relevance to clinical outcomes remains controversial. Therefore, we evaluated the extent of the nuclear expression of phosphorylated STAT3 (pSTAT3), a surrogate marker of signal transducer and activator of transcription 3 (STAT3) activation, by immunohistochemistry. We also analyzed the potential relationship between pSTAT3 positivity (defined as ≥ 40% positive neoplastic cells) and clinicopathologic characteristics in 294 patients with DLBCL. pSTAT3 was detected in 122 patients (42%), with a higher rate in the non-GCB subtype than in the GCB subtype (57% vs. 28%, P < 0.001). Factors potentially activating STAT3, MYD88L265P, and Epstein-Barr virus-encoded small RNA were identified in the pSTAT3-positive non-GCB subtype, whereas the pSTAT3-positive GCB subtype often showed STAT3 mutations and lacked EZH2 mutations and the rearrangements of BCL2 and MYC. Multivariate analyses revealed that the pSTAT3-positive GCB subtype showed a favorable prognosis (HR: 0.17; 95% confidence interval, 0.04-0.7; P = 0.014). These findings suggest that pSTAT3 positivity may have a unique impact on the clinicopathologic characteristics of DLBCL, making it a promising novel marker for the favorable prognosis of patients with the GCB subtype.

DOI： 10.1097/PAS.0000000000001691

Frequent genetic alterations in immune checkpoint-related genes in intravascular large B-cell lymphoma.

Shimada K, Yoshida K, Suzuki Y, Iriyama C, Inoue Y, Sanada M, Kataoka K, Yuge M, Takagi Y, Kusumoto S, Masaki Y, Ito T, Inagaki Y, Okamoto A, Kuwatsuka Y, Nakatochi M, Shimada S, Miyoshi H, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Shiozawa Y, Nannya Y, Okabe A, Kohno K, Atsuta Y, Ohshima K, Nakamura S, Ogawa S, Tomita A, Kiyoi H

Blood Vol. 137 ( 11 ) page： 1491 - 1502 2021.3

Unusual presentation of recurrent follicular lymphoma as diffuse granular shadow

Ito Takayasu, Okachi Shotaro, Ishikawa Yuichi, Shimada Satoko, Wakahara Keiko, Hashimoto Naozumi

RESPIROLOGY CASE REPORTS Vol. 9 ( 3 ) page： e00710 2021.3

Diagnostic utility of programmed cell death ligand 1 (clone SP142) immunohistochemistry for malignant lymphoma and lymphoproliferative disorders: A brief review

Sakakibara Ayako, Kohno Kei, Ishikawa Eri, Suzuki Yuka, Tsuyuki Yuta, Shimada Satoko, Shimada Kazuyuki, Satou Akira, Takahara Taishi, Ohashi Akiko, Takahashi Emiko, Kato Seiichi, Nakamura Shigeo, Asano Naoko

Journal of Clinical and Experimental Hematopathology Vol. 61 ( 4 ) page： 182 - 191 2021

Language：Japanese Publisher：The Japanese Society for Lymphoreticular Tissue Research

The programmed cell death 1 (PD1)/PD1 ligand (PD-L1) axis plays an important role in tumor cell escape from immune control and has been most extensively investigated for therapeutic purposes. However, PD-L1 immunohistochemistry is still not used widely for diagnosis. We review the diagnostic utility of PD-L1 (by clone SP142) immunohistochemistry in large-cell lymphomas, mainly consisting of classic Hodgkin lymphoma (CHL) and diffuse large B-cell lymphoma (DLBCL). Neoplastic PD-L1 (nPD-L1) expression on Hodgkin and Reed-Sternberg cells is well-established among prototypic CHL. Of note, EBV+ CHL often poses a challenge for differential diagnosis from peripheral T-cell lymphoma with EBV+ non-malignant large B-cells; their distinction is based on the lack of PD-L1 expression on large B-cells in the latter. The nPD-L1 expression further provides a good diagnostic consensus for CHL with primary extranodal disease conceivably characterized by a combined pathogenesis of immune escape of tumor cells and immunodeficiency. Compared with CHL, the nPD-L1 expression rate is much lower in DLBCL, highlighting some specific subgroups of intravascular large B-cell lymphoma, primary mediastinal large B-cell lymphoma, and EBV+ DLBCL. They consist of nPD-L1-positive and -negative subgroups, but their clinicopathological significance remains to be elucidated. Microenvironmental PD-L1 positivity on immune cells may be associated with a favorable prognosis in extranodal DLBCL. PD-L1 (by SP142) immunohistochemistry has helped us to understand the immune biology of lymphoid neoplasms possibly related by immune escape and/or immunodeficiency. However, knowledge of these issues remains limited and should be clarified for diagnostic consensus in the future.

DOI： 10.3960/jslrt.21003

Lymphocyte-depleted classic Hodgkin lymphoma with primary extranodal disease: Two cases that highlight the combination of immunodeficiency and immune escape in the pathogenesis

CiNii Research

Tsuyuki Yuta, Kohno Kei, Inagaki Yuichiro, Sakai Yu, Kosugi Hiroshi, Takahashi Emiko, Suzuki Yuka, Shimada Satoko, Kato Seiichi, Takahara Taishi, Satou Akira, Shimoyama Yoshie, Nakamura Shigeo, Asano Naoko, Sakakibara Ayako

Journal of Clinical and Experimental Hematopathology Vol. 61 ( 3 ) page： 173 - 179 2021

Language：Japanese Publisher：The Japanese Society for Lymphoreticular Tissue Research

Neoplastic programmed cell death ligand 1 (PD-L1) expression, activated by PD-L1 gene alterations, is strongly associated with classic Hodgkin lymphoma (CHL). This association enabled a diagnostic consensus for lymphocyte-depleted CHL (LD-CHL), a previously enigmatic disease. We describe two patients with LD-CHL and primary extranodal disease. One patient was a 92-year-old female (Case #1) with a large mass that involved the uterus combined with swollen lymph nodes in the pelvic cavity. The second patient was a 76-year-old female (Case #2) with human T-cell leukemia virus type 1 (HTLV-1) who initially exhibited massive bone marrow involvement without peripheral lymphadenopathies. Biopsies of these tumors from the cervix uteri and bone marrow, respectively, revealed lesions rich in Hodgkin and Reed-Sternberg (H-RS) cells and diminished populations of other cell populations. Immunohistochemistry demonstrated that these H-RS cells expressed CD30, BOB1, and fascin, but not CD15, CD20, PAX5, or OCT2. They also expressed PD-L1, which led to our preferred diagnosis of LD-CHL in both patients. Epstein-Barr virus was associated with LD-CHL in Case #1, but not in Case #2. Both patients were deemed too frail for treatment. They died of disease at 1 (Case #1) and 15 months (Case #2) after the diagnosis. These findings highlight the abnormal biological behavior of this immune-escape-related lymphoid neoplasm in patients with immunodeficiency due to immune senescence and HTLV1 infection.

DOI： 10.3960/jslrt.21008