作者：CY Liu

Supplementation of Probiotic Butyricicoccus pullicaecorum Mediates Anticancer Effect on Bladder Urothelial Cells by Regulating Butyrate-Responsive Molecular Signatures

/ CY Liu / 發表迴響

Yen-Chieh Wang 1 2, Wei-Chi Ku 2, Chih-Yi Liu 2 3, Yu-Che Cheng 2 4 5, Chih-Cheng Chien 2 6, Kang-Wei Chang 7 8, Chi-Jung Huang 4 9

Affiliations
  1. Department of Urology, Cathay General Hospital, Taipei 106438, Taiwan.
  2. School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei 242062, Taiwan.
  3. Department of Pathology, Sijhih Cathay General Hospital, New Taipei 221037, Taiwan.
  4. Department of Medical Research, Cathay General Hospital, Taipei 106438, Taiwan.
  5. Department of Biomedical Sciences and Engineering, National Central University, Taoyuan 320317, Taiwan.
  6. Department of Anesthesiology, Cathay General Hospital, Taipei 106438, Taiwan.
  7. Taipei Neuroscience Institute, Taipei Medical University, Taipei 110301, Taiwan.
  8. Laboratory Animal Center, Taipei Medical University, Taipei 110301, Taiwan.
  9. Department of Biochemistry, National Defense Medical Center, Taipei 114201, Taiwan.

ABSTRACT

In bladder cancer, urothelial carcinoma is the most common histologic subtype, accounting for more than 90% of cases. Pathogenic effects due to the dysbiosis of gut microbiota are localized not only in the colon, but also in regulating bladder cancer distally. Butyrate, a short-chain fatty acid produced by gut microbial metabolism, is mainly studied in colon diseases. Therefore, the resolution of the anti-cancer effects of butyrate-producing microbes on bladder urothelial cells and knowledge of the butyrate-responsive molecules must have clinical significance. Here, we demonstrate a correlation between urothelial cancer of the bladder and Butyricicoccus pullicaecorum. This butyrate-producing microbe or their metabolite, butyrate, mediated anti-cancer effects on bladder urothelial cells by regulating cell cycle, cell growth, apoptosis, and gene expression. For example, a tumor suppressor against urothelial cancer of the bladder, bladder cancer-associated protein, was induced in butyrate-treated HT1376 cells, a human urinary bladder cancer cell line. In conclusion, urothelial cancer of the bladder is a significant health problem. To improve the health of bladder urothelial cells, supplementation of B. pullicaecorum may be necessary and can further regulate butyrate-responsive molecular signatures.

Keywords: Butyricicoccus pullicaecorum; apoptosis; bladder cancer-associated protein; butyrate; urothelial bladder cancer.

>Diagnostics (Basel). 2021 Dec 4;11(12):2270. doi: 10.3390/diagnostics11122270.

7. Supplementation of Probiotic Butyricicoccus pullicaecorum Mediates Anticancer Effect (參考著作)下載

Diagnostic clues for differentiating Merkel cell carcinoma from lymphoma in fine-needle aspiration cytology

/ CY Liu / 發表迴響

Chih-Yi Liu 1 2, Feng-Jie Lai 3, Sheng-Tsung Chang 4 5, Shih-Sung Chuang 4

Affiliations
  1. Division of Pathology, Sijhih Cathay General Hospital, New Taipei City, Taiwan.
  2. College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
  3. Department of Dermatology, Chi-Mei Medical Center, Tainan, Taiwan.
  4. Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan.
  5. Department of Nursing, National Tainan Institute of Nursing, Tainan, Taiwan.

ABSTRACT

Nodal fine needle aspiration (FNA) is usually the first procedure in the work-up of malignancy of unknown primary. Merkel cell carcinoma (MCC) is an aggressive cutaneous cancer more common in Caucasians but rare among Asians. It is a diagnostic challenge in evaluating FNA from a metastatic MCC without the knowledge of a current or prior history of skin cancer. We report the case of a Taiwanese male with cervical and axillary masses. The diagnosis of the FNA from the axillary lymph node was lymphoproliferative lesion suspicious for lymphoma. The histopathological evaluation of nodal biopsy revealed a metastatic neuroendocrine carcinoma and the subsequent excision of the right palm tumor confirmed MCC. Retrospective review of the FNA and imprint cytology smears of the nodal biopsy showed nuclear molding, Indian filing and rare cytoplasmic pale bodies, but no lymphoglandular bodies. Cytologically metastatic MCC may mimic small round cell tumor including lymphoma, we consider these three cytological features as additional diagnostic clues for metastatic MCC. In this report, we present the cytologic and pathological features of this metastatic MCC and discuss the differential diagnosis of the cytologic mimickers.

Keywords: Indian filing; Merkel cell carcinoma; cytoplasmic pale body; fine-needle aspiration cytology; nuclear molding.

< Case Reports >Diagn Cytopathol. 2022 Jan;50(1):E23-E27. doi: 10.1002/dc.24872. Epub 2021 Sep 7.

6. Diagnostic clues for differentiating Merkel cell carcinoma from lymphoma (參考著作)下載

Constitutive Cytomorphologic Features of Medullary Thyroid Carcinoma Using Different Staining Methods

/ CY Liu / 發表迴響

Chih-Yi Liu 1, 2, Chien-Chin Chen 3, 4, Andrey Bychkov 5, 6, Shipra Agarwal 7, Yun Zhu 8, Jen-Fan Hang 9, Chiung-Ru Lai 9, 10, Hee Young Na 11, So Yeon Park 11, Weiwei Li 12, Zhiyan Liu 13, Deepali Jain 7, Ayana Suzuki 14, Mitsuyoshi Hirokawa 14, Noel Chia 15, Min En Nga 15, Tikamporn Jitpasutham 16, Somboon Keelawat 16, Shinya Satoh 17, Dilini Gunawardena 18, Priyanthi Kumarasinghe 18, Chan Kwon Jung 19, Kennichi Kakudo 20

Affiliations
  1. Division of Pathology, Sijhih Cathay General Hospital, New Taipei City 221, Taiwan.
  2. School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 221, Taiwan.
  3. Department of Pathology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi 600, Taiwan.
  4. Department of Cosmetic Science, Chia Nan University of Pharmacy and Science, Tainan 717, Taiwan.
  5. Department of Pathology, Kameda Medical Center, Kamogawa, Chiba 296-8602, Japan.
  6. Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan.
  7. Department of Pathology, All India Institute of Medical Sciences, New Delhi 110029, India.
  8. Department of Pathology, Jiangsu Institution of Nuclear Medicine, Wuxi 214063, China.
  9. Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei 112, Taiwan.
  10. School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.
  11. Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea.
  12. Department of Pathology, Shandong University School of Basic Medical Sciences, Jinan 250012, China.
  13. Department of Pathology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China.
  14. Department of Diagnostic Pathology and Cytology, Kuma Hospital, Kobe 650-0011, Japan.
  15. Department of Pathology, National University Hospital, Singapore 119074, Singapore.
  16. Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
  17. Department of Endocrine Surgery, Yamashita Thyroid and Parathyroid Clinic, Fukuoka 812-0034, Japan.
  18. School of Pathology & Laboratory Medicine, University of Western Australia, Perth, WA 6009, Australia.
  19. Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
  20. Department of Pathology and Thyroid Disease Center, Izumi City General Hospital, Izumi, Osaka 594-0073, Japan.

ABSTRACT

(1) Background: Accurate preoperative identification of medullary thyroid carcinoma (MTC) is challenging due to a spectrum of cytomorphologic features. However, there is a scarcity of studies describing the cytomorphologic features as seen on fine-needle aspiration (FNA) smears prepared using different staining methods. (2) Methods: We performed a retrospective study on MTC cases with available FNA slides from 13 hospitals distributed across 8 Asia-Pacific countries. The differences in the constitutive cytomorphologic features of MTC with each cytopreparatory method were recorded. A comparative analysis of cytologic characteristics was carried out with appropriate statistical tests. (3) Results: Of a total of 167 MTC samples retrospectively recruited, 148 (88.6%) were interpreted as MTC/suspicious for MTC (S-MTC). The staining methods used were Papanicolaou, hematoxylin-eosin, and Romanowsky stains. Seven out of the eleven cytologic criteria can be readily recognized by all three cytopreparatory methods: high cellularity, cellular pleomorphism, plasmacytoid cells, round cells, dyshesive cells, salt-and-pepper chromatin, and binucleation or multinucleation. An accurate diagnosis was achieved in 125 (84.5%) of the 148 samples whose FNAs exhibited five or more atypical features. Conclusions: The present work is the first study on MTC to compare the morphological differences among the cytologic staining techniques. We investigated the constitutive features and the reliability of diagnostic parameters. A feasible scoring system based upon cytomorphologic data alone is proposed to achieve a high degree of diagnostic accuracy.

Keywords: cytology; fine-needle aspiration; medullary thyroid carcinoma; sensitivity; specificity; thyroid.

>Diagnostics (Basel). 2021 Aug 2;11(8):1396. doi: 10.3390/diagnostics11081396.

5. Constitutive Cytomorphologic Features of Medullary Thyroid Carcinoma Using Different Staining Methods (參考著作)下載

Magnolol may contribute to barrier function improvement on imiquimod-induced psoriasis-like dermatitis animal model via the downregulation of interleukin-23

/ CY Liu / 發表迴響

Jiun-Wen Guo 1 2, Yu-Pin Cheng 3, Chih-Yi Liu 4, Haw-Yueh Thong 5, Yang Lo 3, Chen-Yu Wu 3, Shiou-Hwa Jee 3

Affiliations
  1. Department of Medical Research, Cathay General Hospital, Taipei 10630, Taiwan, R.O.C.
  2. College of Medicine, Fu Jen Catholic University, New Taipei City 24205, Taiwan, R.O.C.
  3. Department of Dermatology, Cathay General Hospital, Taipei 10630, Taiwan, R.O.C.
  4. Division of Pathology, Sijhih Cathay General Hospital, New Taipei City 22174, Taiwan, R.O.C.
  5. Department of Dermatology, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei 11101, Taiwan, R.O.C.

ABSTRACT

Psoriasis is a chronic, recurrent, immune-mediated disease involving the skin and joints. Epidermal hyperproliferation, abnormal keratinocyte differentiation, angiogenesis with blood vessel dilatation, and excess T helper type-1 (Th-1) and Th-17 cell infiltration are the main histopathological features of psoriasis. Magnolol is a polyphenolic compound that exerts its biological properties through a variety of mechanisms such as the NF-κB/MAPK, Nrf2/HO-1 and PI3K/Akt pathways. Magnolol has been demonstrated to exert a number of therapeutic effects on dermatological processes, including acting as an anti-inflammation, antiproliferation and antioxidation agent. However, few studies have been published on the effect of magnolol on psoriasis. Therefore, the present study aimed to elucidate the mechanism of action of magnolol on psoriasis. BALB/c mice were treated topically with imiquimod (IMQ) to induce psoriasis-like dermatitis, and were randomly assigned to the control, vehicle control, low- and high-dose magnolol, and 0.25% desoximetasone ointment treatment groups in order to investigate skin barrier function, any changes in the levels of cytokines and for the histological assessment. High doses of magnolol were indicated to be able to improve the barrier function following IMQ-induced barrier disruption. Magnolol activated peroxisome proliferator-activated receptor-γ, and also significantly inhibited the protein expression of interleukin (IL)-23, IL-1β, IL-6, tumor necrosis factor-α and interferon-γ. However, administering a high dose of magnolol did not lead to any improvement in the clinical and pathological features of the psoriasis severity Taken together, these results demonstrated that downregulation of IL-23 may contribute to barrier function improvement in a psoriatic skin model.

Keywords: imiquimod; interleukin-17; interleukin-23; magnolol; psoriasis; skin barrier.

>>Exp Ther Med. 2021 May;21(5):448. doi: 10.3892/etm.2021.9876. Epub 2021 Mar 1.

3. Magnolol may contribute to barrier function improvement on imiquimod-induced psoriasis-like dermatitis (參考著作)下載

Targeted Sequencing of Taiwanese Breast Cancer with Risk Stratification by the Concurrent Genes Signature: A Feasibility Study

/ CY Liu / 發表迴響

Ching-Shui Huang 1 2, Chih-Yi Liu 3, Tzu-Pin Lu 4, Chi-Jung Huang 5 6, Jen-Hwey Chiu 7 8, Ling-Ming Tseng 8 9, Chi-Cheng Huang 9 10

Affiliations
  1. Division of General Surgery, Department of Surgery, Cathay General Hospital, Taipei 106, Taiwan.
  2. School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
  3. Department of Pathology, Cathay General Hospital Sijhih, New Taipei 221, Taiwan.
  4. Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei 110, Taiwan.
  5. Department of Medical Research, Cathay General Hospital, Taipei 106, Taiwan.
  6. National Defense Medical Center, Department of Biochemistry, Taipei 114, Taiwan.
  7. Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11121, Taiwan.
  8. School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan.
  9. Comprehensive Breast Health Center, Department of Surgery, Taipei Veterans General Hospital, Taipei 1121, Taiwan.
  10. School of Public Health, College of Public Health, National Taiwan University, Taipei 100, Taiwan.

ABSTRACT

Breast cancer is the most common female malignancy in Taiwan, while conventional clinical and pathological factors fail to provide full explanation for prognostic heterogeneity. The aim of the study was to evaluate the feasibility of targeted sequencing combined with concurrent genes signature to identify somatic mutations with clinical significance. The extended concurrent genes signature was based on the coherent patterns between genomic and transcriptional alterations. Targeted sequencing of 61 Taiwanese breast cancers revealed 1036 variants, including 76 pathogenic and 545 likely pathogenic variants based on the ACMG classification. The most frequently mutated genes were NOTCH, BRCA1, AR, ERBB2, FANCA, ATM, and BRCA2 and the most common pathogenic deletions were FGFR1, ATM, and WT1, while BRCA1 (rs1799965), FGFR2 (missense), and BRCA1 (rs1799949) were recurrent pathogenic SNPs. In addition, 38 breast cancers were predicted into 12 high-risk and 26 low-risk cases based on the extended concurrent genes signature, while the pathogenic PIK3CA variant (rs121913279) was significantly mutated between groups. Two deleterious SH3GLB2 mutations were further revealed by multivariate Cox’s regression (hazard ratios: 29.4 and 16.1). In addition, we identified several significantly mutated or pathogenic variants associated with differentially expressed signature genes. The feasibility of targeted sequencing in combination with concurrent genes risk stratification was ascertained. Future study to validate clinical applicability and evaluate potential actionability for Taiwanese breast cancers should be initiated.

Keywords: Taiwan; actionable mutations; breast cancer; concurrent genes; risk stratification; targeted sequencing.

>J Pers Med. 2021 Jun 28;11(7):613. doi: 10.3390/jpm11070613.

4. Targeted Sequencing of Taiwanese Breast Cancer with Risk Stratification (參考著作)下載

Residual risk stratification of Taiwanese breast cancers following curative therapies with the extended concurrent genes signature

/ CY Liu / 發表迴響

Ching-Shui Huang 1 2, Tzu-Pin Lu 3, Chih-Yi Liu 4, Chi-Jung Huang 5 6, Jen-Hwey Chiu 7 8, Yen-Jen Chen 7, Ling-Ming Tseng 9 10, Chi-Cheng Huang 11 12

Affiliations
  1. Division of General Surgery, Department of Surgery, Cathay General Hospital, Taipei, Taiwan.
  2. School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
  3. Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan.
  4. Department of Pathology, Cathay General Hospital SiJhih, New Taipei, Taiwan.
  5. Department of Medical Research, Cathay General Hospital, Taipei, Taiwan.
  6. Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan.
  7. Comprehensive Breast Health Center, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd., Beitou District, Taipei, 11217, Taiwan, ROC.
  8. Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
  9. Comprehensive Breast Health Center, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd., Beitou District, Taipei, 11217, Taiwan, ROC. lmtseng@vghtpe.gov.tw.
  10. School of Medicine, College of Medicine, National Yang-Ming University, Taipei, Taiwan. lmtseng@vghtpe.gov.tw.
  11. Comprehensive Breast Health Center, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd., Beitou District, Taipei, 11217, Taiwan, ROC. chishenh74@gmail.com.
  12. School of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan. chishenh74@gmail.com.

ABSTRACT

Introduction: The aim of the study was to perform digital RNA counting to validate a gene expression signature for operable breast cancers initially treated with curative intention, and the risk of recurrence, distant metastasis, and mortality was predicted.

Methods: Candidate genes were initially discovered from the coherent genomic and transcriptional alternations from microarrays, and the extended concurrent genes were used to build a risk stratification model from archived formalin-fixed paraffin-embedded (FFPE) tissues with the NanoString nCounter.

Results: The extended concurrent genes signature was prognostic in 144 Taiwanese breast cancers (5-year relapse-free survival: 89.8 and 69.4% for low- and high-risk group, log-rank test: P = 0.004). Cross-platform comparability was evidenced from significant and positive correlations for most genes as well as equal covariance matrix across 64 patients assayed for both microarray and digital RNA counting.

Discussion: Archived FFPE samples could be successfully assayed by the NanoString nCounter. The purposed signature was prognostic stratifying breast cancer patients into groups with distinct survival patterns, and clinical applicability of the residual risk model was proved.

Keywords: Breast cancer; Digital RNA counting; Extended concurrent genes; Prognostic signature; Residual risk.

>Breast Cancer Res Treat. 2021 Apr;186(2):475-485. doi: 10.1007/s10549-020-06058-7. Epub 2021 Jan 3.

2. Residual risk stratification of Taiwanese breast cancers following curative therapies (參考著作)下載

Merkel cell carcinoma in Taiwan: a subset is chronic arsenicism-related, and the Merkel cell polyomavirus-negative cases are pathologically distinct from virus-related cases with a poorer outcome

/ CY Liu / 發表迴響

Chih-Yi Liu 1, Yun-Ru Lai 2, Pai-Shan Cheng 3, Wei-Wen Yu 4, Ren Ching Wang 5, Wan-Lin Shen 6, Shih-Sung Chuang 7

Affiliations
  1. Division of Pathology, Sijhih Cathay General Hospital, New Taipei City, Taiwan; School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan; School of Medicine, National Tsing Hua University, Hsinchu City, Taiwan.
  2. Department of Anatomical Pathology, Far Eastern Memorial Hospital, New Taipei City, Taiwan.
  3. Department of Dermatology, Chi Mei Medical Center, Tainan, Taiwan.
  4. Department of Dermatology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
  5. Department of Pathology, China Medical University Hospital, Taichung, Taiwan; Department of Nursing, Hung Kuang University, Taichung, Taiwan.
  6. Department of Pathology, Lio Ying Chi-Mei Hospital, Tainan, Taiwan.
  7. Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan. Electronic address: cmh5301@mail.chimei.org.tw.

ABSTRACT

Merkel cell carcinoma (MCC) is a rare primary neuroendocrine carcinoma of the skin, more frequent in the West than in the East. The pathogenesis is complex, with Merkel cell polyomavirus (MCPyV) and ultraviolet (UV) light being reported to play important roles. In this retrospective study of MCC cases from Taiwan, we analysed the prognostic significance of pathological features and the status of MCPyV and retinoblastoma (Rb) expression. We retrospectively collected MCC cases from five hospitals in Taiwan from 1994 to 2022. We examined the clinical and pathological features, performed immunohistochemical studies for the large T antigen of MCPyV and Rb, and reviewed medical records from electronic data. Disease-specific survival was estimated by using the Kaplan-Meier estimate and compared between subgroups using log-rank test. The clinical and pathological features and the immunohistochemical profiles between subgroups were compared using the Fisher exact test for categorical variables. The 38 patients were mostly (71%) males, with a median age of 79. In 22 (58%) patients, the tumours occurred in sun-exposed areas. Clinically, five (13%) patients had chronic arsenicism. Histopathologically, 11 (29%) cases showed combined tumours (MCC with squamous cell carcinoma or Bowen disease/squamous carcinoma in situ). Seventeen (45%) cases were positive for MCPyV, whereas all combined tumours were negative. MCPyV-negative MCC displayed distinctive pathological features, including epidermal changes, presence of an intraepidermal MCC component, linear or single-file growth pattern, and pleomorphic nuclei. Immunohistochemically, 59% (22/37) MCC cases showed complete loss of Rb protein expression, more frequent in MCPyV-unrelated (p<0.001) and combined (p=0.014) cases, ​but without statistical significance among patients with chronic arsenicism, sun exposure, or disease-specific survival. MCPyV-negative cases exhibited a shorter disease-specific survival than MCPyV-positive cases (median overall survival 13 months vs not reached; p=0.041). MCPyV-negative or combined MCCs were associated with a higher disease-specific mortality and poorer prognosis. MCCs occurring in sun-shielded sites, MCPyV-negativity, and combined tumours correlated with a higher disease-specific mortality and a poorer prognosis by multivariable Cox proportional hazard model. The occurrence of MCCs with arsenic exposure was also identified. Our study showed that MCPyV-negative MCC cases in Taiwan exhibited distinctive pathological features and a poorer outcome than MCPyV-related cases. We also confirmed an association of chronic arsenicism with MCC, which might be considered as the third pathogenetic factor after MCPyV and UV light. Further studies including epidemiological and genetic investigations are warranted to elucidate the pathogenesis of MCC in Taiwan, particularly the significance of chronic arsenicism.

Keywords: Merkel cell carcinoma; Merkel cell polyomavirus; UV; arsenic; chronic arsenicism; neuroendocrine carcinoma; skin cancer.

>Pathology. 2025 Apr;57(3):311-319. doi: 10.1016/j.pathol.2024.09.019. Epub 2024 Dec 29.

1. Merkel cell carcinoma in Taiwan(2025)下載

Co-Occurrence of Differentiated Thyroid Cancer and Second Primary Malignancy: Correlation with Expression Profiles of Mismatch Repair Protein and Cell Cycle Regulators

/ CY Liu / 發表迴響

Chih-Yi Liu 1, 2, Ching-Shui Huang 3, 4, Chi-Cheng Huang 5, 6, Wei-Chi Ku 2, Hsing-Yu Shih 3, Chi-Jung Huang 7, 8

Affiliations
  1. Division of Pathology, Sijhih Cathay General Hospital, New Taipei City 221, Taiwan.
  2. School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 242, Taiwan.
  3. Division of General Surgery, Department of Surgery, Cathay General Hospital, Taipei 106, Taiwan.
  4. School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
  5. Comprehensive Breast Health Center, Department of Surgery, Taipei Veterans General Hospital, Taipei 1121, Taiwan.
  6. School of Public Health, College of Public Health, National Taiwan University, Taipei 100, Taiwan.
  7. Department of Medical Research, Cathay General Hospital, Taipei 106, Taiwan.
  8. Department of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan.

ABSTRACT

Some patients with thyroid cancer develop a second primary cancer. Defining the characteristics of patients with double primary cancers (DPCs) is crucial and needs to be followed. In this study, we examine molecular profiles in DPC. We enrolled 71 patients who received thyroid cancer surgery, 26 with single thyroid cancer (STC), and 45 with DPC. A retrograde cohort was used to develop immunohistochemical expressions of mismatch repair (MMR) proteins and cell-cycle-related markers from tissue microarrays to produce an equation for predicting the occurrence of DPC. The multivariate logistic model of 67 randomly selected patients (24 with STC and 43 with DPC) identified that the expression of deficient MMR (dMMR) (odds ratio (OR), 10.34; 95% confidence interval (CI), 2.17-49.21) and pRb (OR, 62.71; 95% CI, 4.83-814.22) were significantly associated with a higher risk of DPC. In contrast, the expression of CDK4 (OR, 0.19; 95% CI, 0.04-0.99) and CDK6 (OR, 0.03; 95% CI, 0.002-0.44) was significantly associated with a lower risk of DPC. Collectively, dMMR, pRb, CDK4, and CDK6 have a sensitivity of 88.9% (95% CI, 75.1-95.8) and a specificity of 69.2% (95% CI, 48.1-84.9) for occurrence of DPC in all 71 patients. This is the first report to demonstrate the molecular differentiation of STC and DPC. Overall, the integral molecular profile performed excellent discrimination and denoted an exponential function to predict the probability of DPC.

Keywords: DNA mismatch repair; cell cycle; immunohistochemistry; multiple primary; neoplasms; second primary; thyroid neoplasms.

>Cancers (Basel). 2021 Oct 31;13(21):5486. doi: 10.3390/cancers13215486.

1. Co-Occurrence of Differentiated Thyroid Cancer and Second Primary Malignancy (代表著作)下載