Details of a Researcher - NISHIHARA, Hiroshi

Papers - NISHIHARA, Hiroshi

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Real-world application of next-generation sequencing-based test for surgically resectable colorectal cancer in clinical practice.

Masayo Ogiri, Ryo Seishima, Kohei Nakamura, Eriko Aimono, Shimpei Matsui, Kohei Shigeta, Tatsuyuki Chiyoda, Shigeki Tanishima, Koji Okabayashi, Hiroshi Nishihara, Yuko Kitagawa

Future oncology (London, England) 2022.07

Accepted, ISSN 1479-6694

Aim: To evaluate the significance of next-generation sequencing-based gene panel testing in surgically resectable colorectal cancer by analyzing real-world data. Materials & methods: A total of 107 colorectal cancer patients who underwent curative surgery were included, and correlations between next-generation sequencing data and clinicopathological findings were evaluated. Results: More combination patterns in gene alteration were identified in advanced-stage tumors than in early-stage tumors. The copy number alteration count was significantly lower in right-sided colon tumors and early-stage tumors. Homologous recombination deficiency was more often identified in advanced-stage tumors, and high homologous recombination deficiency status was useful for identifying high-risk stage II tumors. Conclusion: Homologous recombination deficiency was identified as a useful result of gene panel testing with novel utility in clinical practice.

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A retrospective study of parotid gland tumors at a single institution.

Suzuki S, Bandoh N, Goto T, Kubota A, Uemura A, Kono M, Sato R, Takeda R, Sakaue S, Yamaguchi-Isochi T, Nishihara H, Takei H, Harabuchi Y

Oncology letters 24 ( 1 ) 207 - 207 2022.07

Accepted, ISSN 1792-1074

The aim of the present study was to analyze the clinical characteristics, surgical treatments and clinical outcome of patients with parotid gland tumors and to compare the results with those cited in the literature. A retrospective study was conducted in 140 patients (male, n=77; female, n=63) with parotid gland tumors who underwent parotidectomy at Hokuto Hospital Department of Otolaryngology-Head and Neck Surgery (Obihiro, Japan) between April 2007 and December 2021. Of the 140 patients enrolled, 118 (84.3%) patients had benign tumors, including 63 (45%) patients with pleomorphic adenomas and 43 (30.7%) patients with Warthin tumors, and 22 patients (15.7%) had parotid carcinoma. Comparison of the three groups of patients with parotid gland tumors indicated that pack years as an indicator of smoking status were significantly higher in patients with Warthin tumors than in those with parotid carcinomas (P=0.011) or pleomorphic adenoma (P<0.001). Fine-needle aspiration cytology (FNAC) was non-diagnostic for only 6 (4.3%) of 140 patients. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of FNAC by both conventional smear and liquid-based cytology (LBC) for parotid carcinomas were 70, 99, 93.3, 94.4 and 82.9%, respectively. Among the 22 patients with parotid carcinoma, extended total/total and superficial parotidectomy were performed in 10 (45%) and 11 (50%) cases, respectively. Total and selective neck dissection of the area from level II to I, II and III were performed in 6 (24%) and 7 (32%) patients, respectively. Postoperative radiotherapy (50 Gy) was performed in 15 (68%) patients. The overall survival (OS) and disease-free survival (DFS) rates at 5 years were 51.5 and 76.4%, respectively. Univariate analysis revealed that age >65 years was significantly associated with poorer 5-year OS (P<0.001) and DFS (P<0.001). Multivariate analysis revealed that an age of more than 65 years combined with high-grade histologic malignancy was associated with worse DFS (P=0.02; hazard ratio, 3.628; 95% confidence interval, 1.283-9.514). In conclusion, the clinical characteristics and treatment outcomes of parotid gland tumors were consistent with the results of previous reports. Smoking may be closely related to the pathogenesis of Warthin tumors. LBC potentially provides improved accuracy in FNAC.

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Hybridisation chain reaction-based visualisation and screening for lncRNA profiles in clear-cell renal-cell carcinoma.

Ryohei Kufukihara, Nobuyuki Tanaka, Kimiharu Takamatsu, Naoya Niwa, Keishiro Fukumoto, Yota Yasumizu, Toshikazu Takeda, Kazuhiro Matsumoto, Shinya Morita, Takeo Kosaka, Eriko Aimono, Hiroshi Nishihara, Ryuichi Mizuno, Mototsugu Oya

British journal of cancer 127 ( 6 ) 1133 - 1141 2022.06

Accepted, ISSN 0007-0920

BACKGROUND: Analysis of long noncoding RNA (lncRNA) localisation at both the tissue and subcellular levels can provide important insights into the cell types that are important for their function. METHODS: By applying new fluorescent in situ hybridisation technique called hybridisation chain reaction (HCR), we achieved a high-throughput lncRNA visualisation and evaluation of clinical samples. RESULTS: Assessing 1728 pairs of 16 lncRNAs and clear-cell renal-cell carcinoma (ccRCC) specimens, three lncRNAs (TUG1, HOTAIR and CDKN2B-AS1) were associated with ccRCC prognosis. Furthermore, we derived a new lncRNA risk group of ccRCC prognosis by combining the expression levels of these three lncRNAs. Examining genomic alterations underlying this classification revealed prominent features of tumours that could serve as potential biomarkers for targeting lncRNAs. We then derived combination of HCR with expansion microscopy and visualised nanoscale-resolution HCR signals in cell nuclei, uncovering intracellular colocalization of three lncRNA (TUG1, HOTAIR and CDKN2B-AS1) signals such as those located intra- or out of the nucleus or nucleolus in cancer cells. CONCLUSION: LncRNAs are expected to be desirable noncoding targets for cancer diagnosis or treatments. HCR involves plural probes consisting of small DNA oligonucleotides, clinically enabling us to detect cancerous lncRNA signals simply and rapidly at a lower cost.

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Influence of response to prior docetaxel on sensitivity to cabazitaxel in prostate cancer patients with PTEN alterations.

Ken Kamisawa, Takeo Kosaka, Kohei Nakamura, Yota Yasumizu, Hiroshi Hongo, Toshikazu Takeda, Kazuhiro Matsumoto, Hiroshi Nishihara, Mototsugu Oya

Cancer science 113 ( 9 ) 3161 - 3168 2022.06

Accepted, ISSN 1347-9032

The purpose of this study was to investigate factors predicting the sensitivity to cabazitaxel therapy in metastatic castration-resistant prostate cancer (mCRPC) patients with phosphatase and tensin homolog deleted from chromosome 10 (PTEN) alterations. This single-institution, retrospective study included 12 mCRPC patients with PTEN alterations who had received cabazitaxel therapy. Five patients (41%) responded to cabazitaxel therapy with a prostate-specific antigen (PSA) level decline of ≥30% from baseline, and all of them had responded to prior docetaxel therapy with a PSA decline of ≥30%. None of the patients with a poor response to prior docetaxel therapy responded well to cabazitaxel therapy. Of the seven patients who did not respond to cabazitaxel and whose PSA declined from baseline was <30%, five (71%) were also refractory to prior docetaxel therapy. The PSA responses to docetaxel and cabazitaxel were significantly correlated (p = 0.027). Kaplan-Meier analysis revealed that progression-free survival (PFS) for cabazitaxel was significantly shorter for prior docetaxel nonresponders (3.3 versus 9.1 months, p = 0.028). Multivariate analysis revealed that a poor response to prior docetaxel (PSA decline < 30%) (hazard ratio [HR] = 6.382, 95% confidence interval [CI] 1.172-34.750, p = 0.032) and baseline PSA of ≥20 ng/ml (HR = 33.584, 95% CI 2.332-483.671, p = 0.010) were independent prognostic factors for PFS with cabazitaxel therapy. These results demonstrate cross-resistance between docetaxel and cabazitaxel. The response to prior docetaxel therapy can influence the sensitivity to cabazitaxel therapy in mCRPC patients with PTEN alterations.

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A Japanese case of castration-resistant prostate cancer with BRCA2 and RB1 co-loss and TP53 mutation: a case report.

Tomohiro Iwasawa, Takeo Kosaka, Shinya Morita, Shuji Mikami, Kohei Nakamura, Hiroshi Hongo, Hiroshi Nishihara, Mototsugu Oya

BMC medical genomics 15 ( 1 ) 138 - 138 2022.06

Accepted

BACKGROUND: Abnormalities in homologous recombination contribute to the aggressive nature of castration-resistant prostate cancer. Retinoblastoma transcriptional corepressor 1 (RB1) and breast cancer 2 (BRCA2) exist close to each other in the same chromosome, and the significance of their concurrent loss has become a hot topic in the field of cancer research. CASE PRESENTATION: A 61-year-old man presented with a chief complaint of a mass on his head and was diagnosed as multiple bone metastases from prostate cancer. He was treated with standard medication, but he died 2 years 6 months after being diagnosed with prostate cancer. Simultaneous biallelic loss of RB1 and BRCA2 as well as a truncating mutation of tumor protein p53 (TP53) were revealed by genomic analysis. CONCLUSION: To our knowledge, this is the first report of castration-resistant prostate cancer (CRPC) with BRCA2 and RB1 co-loss and TP53 mutation. To establish a treatment strategy for highly malignant cases with such multiple genetic features is important.

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Multiple metastases of androgen indifferent prostate cancer in the urinary tract: two case reports and a literature review.

Tsukasa Masuda, Takeo Kosaka, Kohei Nakamura, Hiroshi Hongo, Kazuyuki Yuge, Hiroshi Nishihara, Mototsugu Oya

BMC medical genomics 15 ( 1 ) 118 - 118 2022.05

Accepted

BACKGROUND: Prostate cancer (PC) is mainly known to metastasize to bone, lung and liver, but isolated metastases of prostate cancer, including ductal carcinoma, in the urinary tract are very rare. We describe two patients with nodular masses in the urinary tract (the anterior urethra or the urinary bladder) that were found on cystoscopy during treatment of castration-resistant prostate cancer. CASE PRESENTATION: In both cases, the pathological diagnosis from transurethral tumor resection showed that they were androgen indifferent prostate cancer (AIPC), including aggressive variant prostate cancer (AVPC) in Case 1 and treatment-induced neuroendocrine differentiation prostate cancer (NEPC) in Case 2. In Case 1, Loss of genetic heterozygosity (LOH) of BRCA2 and gene amplification of KRAS was identified from the urethra polyps. In Case 2, homozygous deletion was observed in PTEN, and LOH without mutation was observed in RB1. CONCLUSION: These are the first reports of two cases of urinary tract metastasis of AIPC.

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The oligodendroglial histological features are not independently predictive of patient prognosis in lower-grade gliomas.

Eriel Sandika Pareira, Makoto Shibuya, Kentaro Ohara, Yu Nakagawa, Tokunori Kanazawa, Dai Kamamoto, Yasutaka Kato, Eri Arai, Eriko Aimono, Kazunari Yoshida, Hiroshi Nishihara, Yae Kanai, Hikaru Sasaki

Brain tumor pathology 39 ( 2 ) 79 - 87 2022.04

Accepted, ISSN 1433-7398

The relevance of oligodendroglial histological features to patient prognoses is controversial. 93 LrGGs resected for about 2 decades were re-assessed based on WHO2007 with special interest to pure oligodendroglial diagnosis (oligodendroglioma or anaplastic oligodendroglioma) and presence of CFO features. Those histological features, patients OS, and tumor chromosomal/genetic characteristics were correlated each other in each of the 3 IDH-1p/19q-based molecular groups. There was significant association between 1p19q status with the oligodendroglial histological diagnosis as well as presence of CFO in the entire cohort. The oligodendroglial diagnosis was associated with longer OS in IDHmut/codel group; however, this association was not significant in the multivariate analyses. In IDHmut/noncodel and IDH-wildtype groups, the oligodendroglial diagnosis was not associated with patient OS. Presence of CFO was not associated with patient OS in any molecular groups. Gain of 8q was associated with the oligodendroglial diagnosis in IDHmut/noncodel group. Neither the oligodendroglial diagnosis nor CFO was predictive for the methylation status of the MGMT gene in any molecular groups. The oligodendroglial histological features are not independently predictive of either patient prognosis or chemotherapeutic response in LrGGs, leaving the possibility of marginal favorable association only in IDHmut/codel tumors.

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TP53 variants in p53 signatures and the clonality of STICs in RRSO samples.

Tomoko Akahane, Kenta Masuda, Akira Hirasawa, Yusuke Kobayashi, Arisa Ueki, Miho Kawaida, Kumiko Misu, Kohei Nakamura, Shimpei Nagai, Tatsuyuki Chiyoda, Wataru Yamagami, Shigenori Hayashi, Fumio Kataoka, Kouji Banno, Kokichi Sugano, Hajime Okita, Kenjiro Kosaki, Hiroshi Nishihara, Daisuke Aoki

Journal of gynecologic oncology 33 ( 4 ) e50 2022.03

Accepted, ISSN 2005-0380

OBJECTIVE: Precursor lesions may be identified in fallopian tube tissue after risk-reducing salpingo-oophorectomy (RRSO) in patients with pathogenic variants of BRCA1/2. Serous tubal intraepithelial carcinoma (STIC) is considered a precursor of high-grade serous carcinoma, whereas the significance of the p53 signature remains unclear. In this study, we investigated the relationship between the p53 signature and the risk of ovarian cancer. METHODS: We analyzed the clinicopathological findings and conducted DNA sequencing for TP53 variants of p53 signatures and STIC lesions isolated using laser capture microdissection in 13 patients with pathogenic variants of BRCA1/2 who underwent RRSO and 17 control patients with the benign gynecologic disease. RESULTS: TP53 pathogenic variants were detected significantly higher in RRSO group than control (p<0.001). No difference in the frequency of p53 signatures were observed between groups (53.8% vs 29.4%; p=0.17). TP53 sequencing and next-generation sequencing analysis in a patient with STIC and occult cancer revealed 2 TP53 mutations causing different p53 staining for STICs and another TP53 mutation shared between STIC and occult cancer. CONCLUSION: The sequence analysis for TP53 revealed 2 types of p53 signatures, one with a risk of progression to STIC and ovarian cancer with pathological variants in TP53 and the other with a low risk of progression without pathological variants in TP53 as seen in control.

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Maelstrom functions in the production of Siwi-piRISC capable of regulating transposons in Bombyx germ cells.

Namba Y, Iwasaki YW, Nishida KM, Nishihara H, Sumiyoshi T, Siomi MC

iScience (Elsevier BV) 25 ( 3 ) 103914 - 103914 2022.03

Accepted, ISSN 2589-0042

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Unique characteristics of tertiary lymphoid structures in kidney clear cell carcinoma: prognostic outcome and comparison with bladder cancer.

Tsukasa Masuda, Nobuyuki Tanaka, Kimiharu Takamatsu, Kyohei Hakozaki, Ryohei Takahashi, Tadatsugu Anno, Ryohei Kufukihara, Kazunori Shojo, Shuji Mikami, Toshiaki Shinojima, Kazuhiro Kakimi, Tatsuhiko Tsunoda, Eriko Aimono, Hiroshi Nishihara, Ryuichi Mizuno, Mototsugu Oya

Journal for immunotherapy of cancer 10 ( 3 ) 2022.03

Accepted

BACKGROUND: The aims of this study were (1) to clarify the impact of tertiary lymphoid structure (TLS) status on the outcome and immunogenomic profile of human clear cell renal cell carcinoma (ccRCC) and (2) to determine phenotypic differences in TLSs between different types of genitourinary cancer, that is, urinary ccRCC and bladder cancer. METHODS: We performed a quantitative immunohistological analysis of ccRCC tissue microarrays and conducted integrated genome mutation analysis by next-generation sequencing and methylation array analysis. Since the tumor immune microenvironment of ccRCC often differs from that of other cancer types, we analyzed the phenotypic differences in TLSs between ccRCC and in-house bladder cancer specimens. RESULTS: Varying distribution patterns of TLSs were observed throughout ccRCC tumors, revealing that the presence of TLSs was related to poor prognosis. An analysis of genomic alterations based on TLS status in ccRCC revealed that alterations in the PI3K-mTOR pathway were highly prevalent in TLS-positive tumors. DNA methylation profiling also revealed distinct differences in methylation signatures among ccRCC samples with different TLS statuses. However, the TLS characteristics of ccRCC and bladder cancer markedly differed: TLSs had the exact opposite prognostic impact on bladder cancer as on ccRCC. The maturity and spatial distribution of TLSs were significantly different between the two cancer types; TLSs were more mature with follicle-like germinal center organization and likely to be observed inside the tumor in bladder cancer. Labeling for CD8, FOXP3, PD-1, and PD-L1 showed marked differences in the diversity of the immune microenvironment surrounding TLSs. The proportions of CD8-, FOXP3-, and PD-L1-positive cells were significantly higher in TLSs in bladder cancer than in TLSs in ccRCC; rather the proportion of PD-1-positive cells was significantly higher in TLSs in ccRCC than in TLSs in bladder cancer. CONCLUSION: The immunobiology of ccRCC is unique, and various cancerous phenomena conflict with that seen in other cancer types; therefore, comparing the TLS characteristics between ccRCC and bladder cancer may help reveal differences in the prognostic impact, maturity and spatial distribution of TLSs and in the immune environment surrounding TLSs between the two cancers.

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[Crosstalk of Cancer Genomic Test and Cancer Immune Therapy].

Nishihara H

Gan to kagaku ryoho. Cancer & chemotherapy 49 ( 3 ) 248 - 254 2022.03

Accepted, ISSN 0385-0684

Sclerosing Polycystic Adenosis Arising in the Parotid Gland Without PI3K Pathway Mutations.

Uemura A, Bandoh N, Goto T, Sato R, Suzuki S, Kubota A, Yamaguchi T, Baba S, Kato Y, Nishihara H, Harabuchi Y, Takei H

Head and neck pathology 16 ( 1 ) 282 - 287 2022.03

Accepted, ISSN 1936-055X

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Castration-resistant prostate cancer patient presenting with whole genome doubling with CDK-12 mutation.

Yuto Baba, Takeo Kosaka, Hiroaki Kobayashi, Kohei Nakamura, Shuji Mikami, Hiroshi Nishihara, Makoto Nakanishi, Mototsugu Oya

BMC medical genomics 15 ( 1 ) 32 - 32 2022.02

Accepted

BACKGROUND: The use of whole-genome sequencing in clinical practice has revealed variable genomic characteristics across cancer types, one of which is whole-genome doubling (WGD), which describes the duplication of a complete set of chromosomes. Yet it is relatively rare in prostate cancer and no such case has ever been reported in Japanese patients. CASE PRESENTATION: A 54-year-old patient with prostatic adenocarcinoma with bone and lymph node metastases was started on androgen-deprivation therapy. As the prostate cancer turned castration-resistant, multimodal therapies including taxane- and platinum-based chemotherapy, androgen-receptor antagonist inhibitors, radiotherapy and radium-233 were introduced. Good controls of serum prostate-specific antigen (PSA) level and bone metastases were achieved for more than 13 years since after the initial treatment. During the treatment, a metastatic lymph node biopsy was performed to confirm the tumor histology, and spinal decompression surgery were performed for spinal compression due to lumber vertebral metastases. The immunohistochemical analysis identified PSA and androgen receptor positive tumor cells in both metastatic lesions, while no variable cancer cells were detected in the prostate on second biopsy. Whole-genome sequencing was performed on the biopsied metastatic lymph node in search for another possible treatment and it revealed that the tumor had WGD and CDK12 mutation. The WGD-positive tumor cells contained large and polymorphic nucleus, presumably reflecting on the ploidy abnormality of the chromosomes. CONCLUSIONS: This report is the first case of a Japanese patient presenting with WGD, who survived more than 13 years with multimodal chemotherapies and radiotherapies.

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Precision cancer genome testing needs proficiency testing involving all stakeholders.

Maekawa M, Taniguchi T, Nishio K, Sakai K, Matsushita K, Nakatani K, Ishige T, Ikejiri M, Nishihara H, Sunami K, Yatabe Y, Hatanaka KC, Hatanaka Y, Yamamoto Y, Fukuyama K, Oda S, Saito K, Yokomura M, Kubo Y, Sato H, Tanaka Y, Fuchioka M, Yamasaki T, Matsuda K, Kurachi K, Funai K, Baba S, Iwaizumi M

Scientific reports 12 ( 1 ) 1494 2022.01

Accepted

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First successful case of platinum-based chemotherapy for neuroendocrine prostate cancer with BRCA2 and PTEN alterations.

Minami Omura, Takeo Kosaka, Eriko Aimono, Kohei Nakamura, Hiroshi Hongo, Shuji Mikami, Hiroshi Nishihara, Mototsugu Oya

IJU case reports 5 ( 1 ) 41 - 44 2022.01

Accepted

INTRODUCTION: Deoxyribonucleic acid repair gene mutations are now being studied in a variety of solid tumors, with the hope of predicting prognosis, pathogenesis, and treatment outcomes. CASE PRESENTATION: We report the case of a Japanese patient with advanced castration-resistant prostate cancer who exhibited a prominent response to platinum therapy and had coexisting BRCA2 and PTEN mutations according to retrospective multigene panel analysis. CONCLUSION: Through a review of clinical outcomes and genetic/pathologic profiling, the presented case provides insights into future management strategies based on the tumor genetic status.

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SARS-CoV-2 RT-qPCR testing of pooled saliva samples: A case study of 824 asymptomatic individuals and a questionnaire survey in Japan.

Junna Oba, Hiroaki Taniguchi, Masae Sato, Masaki Takanashi, Moe Yokemura, Yasunori Sato, Hiroshi Nishihara

PloS one 17 ( 5 ) e0263700 2022

Accepted

From the beginning of the COVID-19 pandemic, the demand for diagnostic and screening tests has exceeded supply. Although the proportion of vaccinated people has increased in wealthier countries, breakthrough infections have occurred amid the emergence of new variants. Pooled-sample COVID-19 testing using saliva has been proposed as an efficient, inexpensive, and non-invasive method to allow larger-scale testing, especially in a screening setting. In this study, we aimed to evaluate pooled RT-qPCR saliva testing and to compare the results with individual tests. Employees of Philips Japan, Ltd. were recruited to participate in COVID-19 screening from October to December 2020. Asymptomatic individuals (n = 824) submitted self-collected saliva samples. Samples were tested for the presence of SARS-CoV-2 by RT-qPCR in both 10-sample pools and individual tests. We also surveyed participants regarding their thoughts and behaviors after the PCR screening project. Two of the 824 individuals were positive by RT-qPCR. In the pooled testing, one of these two had no measurable Ct value, but showed an amplification trend at the end of the PCR cycle. Both positive individuals developed cold-like symptoms, but neither required hospitalization. Of the 824 participants, 471 responded to our online questionnaire. Overall, while respondents agreed that PCR screening should be performed regularly, the majority were willing to undergo PCR testing only when it was provided for free or at low cost. In conclusion, pooled testing of saliva samples can support frequent large-scale screening that is rapid, efficient, and inexpensive.

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Landscape of prognostic signatures and immunogenomics of the AXL/GAS6 axis in renal cell carcinoma.

Kyohei Hakozaki, Nobuyuki Tanaka, Kimiharu Takamatsu, Ryohei Takahashi, Yota Yasumizu, Shuji Mikami, Toshiaki Shinojima, Kazuhiro Kakimi, Takashi Kamatani, Fuyuki Miya, Tatsuhiko Tsunoda, Eriko Aimono, Hiroshi Nishihara, Ryuichi Mizuno, Mototsugu Oya

British journal of cancer 125 ( 11 ) 1533 - 1543 2021.11

Accepted, ISSN 0007-0920

BACKGROUND: Cabozantinib is an oral tyrosine kinase inhibitor in renal cell carcinoma (RCC), whose targets include oncogenic AXL and unique ligand GAS6. Critical gaps in basic knowledge need to be addressed to devise an exclusive biomarker and candidate when targeting the AXL/GAS6 axis. METHODS: To clarify the effects of the AXL/GAS6 axis on RCC, we herein performed a large-scale immunogenomic analysis and single-cell counts including various metastatic organs and histological subtypes of RCC. We further applied genome-wide mutation analyses and methylation arrays. RESULTS: Varying patterns of AXL and GAS6 expression were observed throughout primary RCC tumours and metastases. Scoring individual AXL/GAS6 levels in the tumour centre and invasive margin, namely, the AXL/GAS6 score, showed a good ability to predict the prognosis of clear cell RCC. Metastasis- and histological subtype-specific differences in the AXL/GAS6 score existed since lung metastasis and the papillary subtype were weakly related to the AXL/GAS6 axis. Cell-by-cell immunohistological assessments clarified an immunosuppressive environment in tumours with high AXL/GAS6 scores. Genomic alterations in the PI3K-mTOR pathway and DNA methylation profiling revealed distinct differences with the AXL/GAS6 score in ccRCC. CONCLUSION: The AXL/GAS6 scoring system could predict the outcome of prognosis and work as a robust biomarker for the immunogenomic state in RCC.

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A first case of ductal adenocarcinoma of the prostate having characteristics of neuroendocrine phenotype with PTEN, RB1 and TP53 alterations.

Hiroaki Kobayashi, Takeo Kosaka, Kohei Nakamura, Kazunori Shojo, Hiroshi Hongo, Shuji Mikami, Hiroshi Nishihara, Mototsugu Oya

BMC medical genomics 14 ( 1 ) 245 - 245 2021.10

Accepted

BACKGROUND: Ductal adenocarcinoma and neuroendocrine cancer are rare subtypes of prostate cancer with poor prognosis and limited therapeutic options. We present the first case of ductal adenocarcinoma having a neuroendocrine phenotype. CASE PRESENTATION: A 63-year-old man presented with gross hematuria and urinary retention, and his serum prostate-specific antigen level was 4.58 ng/mL. We performed transurethral resection of the prostate, and the diagnosis was ductal adenocarcinoma with a Gleason score of 5 + 4 for acinar adenocarcinoma. Magnetic resonance imaging showed local invasion of left lobe of the prostate and bone metastasis of the left trochanteric section of the femur. Multidisciplinary treatments such as androgen deprivation therapy, chemoradiation therapy, and surgery for metastatic lesions have led to long-term survival. Since next-generation sequencing revealed PTEN and RB1 co-loss and TP53 mutations, we re-evaluated the immunohistochemistry and he was found to be positive for synaptophysin. CONCLUSIONS: This is the first Japanese case of ductal adenocarcinoma with a neuroendocrine phenotype. Genetic analysis may help not only guide the therapeutic strategies, but also sometimes with the diagnosis.

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Concordance analysis of microsatellite instability status between polymerase chain reaction based testing and next generation sequencing for solid tumors.

Keitaro Shimozaki, Hideyuki Hayashi, Shigeki Tanishima, Sara Horie, Akihiko Chida, Kai Tsugaru, Kazuhiro Togasaki, Kenta Kawasaki, Eriko Aimono, Kenro Hirata, Hiroshi Nishihara, Takanori Kanai, Yasuo Hamamoto

Scientific reports 11 ( 1 ) 20003 - 20003 2021.10

Accepted

Various malignancies exhibit high microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR). The MSI-IVD kit, a polymerase chain reaction (PCR)-based method, was the first tumor-agnostic companion diagnostic to detect MSI status in MSI-H solid tumors. Recently, next-generation sequencing (NGS), which can also detect MSI-H/dMMR, has been made clinically available; however, its real-world concordance with PCR-based testing of MSI-H/dMMR remains to be investigated. The co-primary end points included the positive and negative predictive values of MSI-H/dMMR. A retrospective analysis of 80 patients who had undergone both MSI testing and NGS between July 2015 and March 2021 was conducted. Five patients were confirmed to have MSI-H in both examinations. Among the 75 patients diagnosed as microsatellite stable (MSS) by PCR-based testing, one with pancreatic cancer was diagnosed as having MSI-H after NGS. One patient with pancreatic cancer was diagnosed as having MSS in both tests was found to have a mutation in MLH1 by NGS, which was confirmed as dMMR by IHC staining. NGS had positive and negative predictive values of 100% (5/5) and 98.7% (74/75), respectively, for MSI-H. The concordance between NGS and PCR-based testing was 98.8% (79/80). Thus, NGS can be useful for evaluating MSI/MMR status in clinical practice and can be an important alternative method for detecting MSI-H/dMMR in the future.

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胸壁CIC-NUTM1 sarcomaの1例

岡田真彦, 池村辰之介, 江本桂, 西原広史, 林玲奈, 冨保紗希, 齋藤彩夏, 福島貴大, 篠崎太郎, 光石彬史, 胡谷俊樹, 寺井秀樹, 安田浩之, 川田一郎, 副島研造, 福永興壱

肺癌 ((NPO)日本肺癌学会) 61 ( 6 ) 778 - 778 2021.10

Accepted, ISSN 0386-9628

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