Cancer Research and Treatment

Original Articles

Noninvasive Assessment of Ki-67 Expression in Breast Cancer Using Ultrasound Radiomics: A Multi-Institutional Study: Sijie Mo, Zhibin Huang, Jing Zheng, Huaiyu Wu, Shuzhen Tang, Mengyun Wang, Jinfeng Xu, Hongtian Tian, Xiaoli Huang, Fajin Dong; Received May 30, 2025 Accepted September 2, 2025 Published online September 5, 2025; DOI: https://doi.org/10.4143/crt.2025.581 [Epub ahead of print]

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Purpose
This study aimed to develop and rigorously evaluate machine learning models using ultrasound (US) breast cancer (BC) images to predict Ki-67 expression. Additionally, the study sought to identify independent factors influencing Ki-67 expression, with further test conducted through external datasets.
Materials and Methods
This study analyzed US images of BC from 347 patients (training set: n=230; external test set: n=117) from Shenzhen People’s Hospital and Guangxi Academy of Medical Sciences. Radiomic features were extracted using manual region-of-interest delineation and the Pyradiomics package. Feature selection was performed using Least Absolute Shrinkage and Selection Operator (LASSO) and decision tree analysis, resulting in 16 features. Machine learning models—logistic regression (LR), support vector machine (SVM), and multilayer perceptron (MLP)—were developed, and their performance was assessed using the area under the receiver operating characteristic curve, accuracy, sensitivity, specificity, and decision curve analysis. Statistical analysis included univariate and multivariate logistic regression.
Results
Three machine learning models (LR, SVM, and MLP) were developed to predict Ki-67 expression from US images. The LR model demonstrated the best diagnostic performance, with an area under the curve of 0.800 in external test set. Key predictors of Ki-67 expression included ill-defined maximum mass diameter and human epidermal growth factor receptor 2 expression, along with other significant clinical variables.
Conclusion
This dual-center study demonstrates the potential of radiomics models based on US BC images to predict Ki-67 expression accurately. As a non-invasive diagnostic tool, this approach offers valuable support for clinical decision-making and personalized treatment planning in BC patients.

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Utility of Ki-67 index combined with alpha-fetoprotein and lactate dehydrogenase in distinguishing mature from immature ovarian teratomas in children
Xiazhe Li, Zhiyong Zhong, Yanwei Qi, Yingxin Gong
Frontiers in Neurology.2026;[Epub] CrossRef

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Breast cancer

Changes in Invasive Breast Carcinomas after Neoadjuvant Chemotherapy Can Influence Adjuvant Therapeutic Decisions: Bárbara Jaime dos Santos, Débora Balabram, Virginia Mara Reis Gomes, Carolina Costa Café de Castro, Paulo Henrique Costa Diniz, Marcelo Araújo Buzelin, Cristiana Buzelin Nunes; Cancer Res Treat. 2024;56(1):178-190. Published online August 1, 2023; DOI: https://doi.org/10.4143/crt.2023.386

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Purpose
Neoadjuvant chemotherapy (NACT) can change invasive breast carcinomas (IBC) and influence the patients’ overall survival time (OS). We aimed to identify IBC changes after NACT and their association with OS.
Materials and Methods
IBC data in pre- and post-NACT samples of 86 patients were evaluated and associated with OS.
Results
Post-NACT tumors changed nuclear pleomorphism score (p=0.025); mitotic count (p=0.002); % of tumor-infiltrating inflammatory cells (p=0.016); presence of in situ carcinoma (p=0.001) and lymphovascular invasion (LVI; p=0.002); expression of estrogen (p=0.003), progesterone receptors (PR; p=0.019), and Ki67 (p=0.003). Immunohistochemical (IHC) profile changed in 26 tumors (30.2%, p=0.050). Higher risk of death was significatively associated with initial tumor histological grade III (hazard ratio [HR], 2.94), high nuclear pleomorphism (HR, 2.53), high Ki67 index (HR, 2.47), post-NACT presence of LVI (HR, 1.90), luminal B–like profile (HR, 2.58), pre- (HR, 2.26) and post-NACT intermediate mitotic count (HR, 2.12), pre- (HR, 4.45) and post-NACT triple-negative IHC profile (HR, 4.52). On the other hand, lower risk of death was significative associated with pre- (HR, 0.35) and post-NACT (HR, 0.39) estrogen receptor–positive, and pre- (HR, 0.37) and post-NACT (HR, 0.57) PR-positive. Changes in IHC profile were associated with longer OS (p=0.050). In multivariate analysis, pre-NACT grade III tumors and pre-NACT and post-NACT triple negative IHC profile proved to be independent factors for shorter OS.
Conclusion
NACT can change tumor characteristics and biomarkers and impact on OS; therefore, they should be reassessed on residual samples to improve therapeutic decisions.

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Prognostic Impact of Real-World Immunohistochemical Changes in Breast Cancer Treated with Neoadjuvant Chemotherapy
Marcelo Antonini, André Mattar, Marcelo Madeira, Letícia Xavier Félix, Julio Antonio Pereira de Araújo, Francisco Pimentel Cavalcante, Felipe Zerwes, Fabricio Palermo Brenelli, Antonio Luis Frasson, Eduardo Camargo Millen, Marina Diógenes Teixeira, Lariss
Clinical Breast Cancer.2026; 26(1): 276. CrossRef
Immunohistochemical Changes After Neoadjuvant Chemotherapy and Their Impact on Breast Cancer Survival: A Systematic Review and Meta-analysis
Marcelo Antonini, André Mattar, Gil Facina, Francisco Pimentel Cavalcante, Felipe Zerwes, Fabricio Palermo Brenelli, Antônio Luis Frasson, Eduardo Camargo Millen, Rodrigo Caires Campos, Letícia Xavier Félix, Juliana Calado Vieira, Marina Diógenes Teixeira
Clinical Breast Cancer.2026; 26(3): 208. CrossRef
Prognostic value of prognostic nutritional index in breast cancer patients receiving neoadjuvant therapy: a systematic review and meta-analysis
Meihui Shan, Ziqian Zhao, Munawar Anwar, Jiawei Chen, Yuquan Dai, Yeliya Yeerboli, Zuqiang Xu, Zizhang Wang, Le Yang, Chao Dong
Frontiers in Oncology.2026;[Epub] CrossRef
Discordance in Immunohistochemistry Results in Breast Pathologies: Effect of Chemotherapy, Specimen Characteristics, or Pathology Center?
Mustafa Ersoy
Clinical Medicine Insights: Oncology.2025;[Epub] CrossRef
Identifying gene expression signatures of oncolytic virus response in patient-derived pancreatic ductal adenocarcinoma organoids
Marco Huberts, Elham Aida Farshadi, Farzana Mohammad, Jie Ju, Andrew Stubbs, Ron A.M. Fouchier, Bernadette G. van den Hoogen
Molecular Therapy Oncology.2025; 33(4): 201064. CrossRef
Post-Surgical Reassessment of Breast Cancer IHC: Concordance, Δ-Metrics, and Treatment-Relevant Reclassification
Ramona Andreea Cioroianu, Michael Schenker, Tradian Ciprian Berisha, Virginia-Maria Rădulescu, George Ovidiu Cioroianu, Raluca Chirculescu, Ana Maria Petrescu, Mihaela Popescu, Anda Lorena Dijmărescu, Stelian Ștefăniță Mogoantă
Diagnostics.2025; 15(24): 3128. CrossRef

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The Use of CD44 Variant 9 and Ki-67 Combination Can Predicts Prognosis Better Than Their Single Use in Early Gastric Cancer: Se-Il Go, Gyung Hyuck Ko, Won Sup Lee, Jeong-Hee Lee, Sang-Ho Jeong, Young-Joon Lee, Soon Chan Hong, Woo Song Ha; Cancer Res Treat. 2019;51(4):1411-1419. Published online February 25, 2019; DOI: https://doi.org/10.4143/crt.2018.663

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Purpose
We previously demonstrated that CD44v9 and Ki-67 played an important role in predicting poor prognosis of early gastric cancer (EGC). However, little is known about combined use of both biomarkers as prognostic biomarker. The present study was performed to investigate the significance of CD44v9 and Ki-67 expression as a combination biomarker for EGC.
Materials and Methods
With tissue microarray for 158 EGC tissues, we performed immunohistochemical staining for CD44v9 and Ki-67. The whole patients were divided into three groups (group A, CD44v9- negative/Ki-67–low; group B, neither group A or C; and group C, CD44v9-positive/Ki-67– high). Its clinical significance was re-analyzed with adjustment via propensity score matching (PSM). For validation, we performed bootstrap resampling.
Results
The median follow-up duration was 90.4 months (range, 3.7 to 120.4 months). In the comparison according to CD44v9/Ki-67 expression, the combined use of the two biomarker clearly separated the three groups by 5-year survival rates (5-YSR, 96.3%, 89.8%, and 76.8% in group A, B, and C, respectively; p=0.009). After PSM, 5-YSR were 97.7% and 76.8% in group A+B and group C, respectively (p=0.002). Multivariable analysis demonstrated that group C had independently poor prognosis (hazard ratio, 9.137; 95% confidence interval, 1.187 to 70.366; p=0.034) compared with group A. Bootstrap resampling internally validated this result (p=0.016).
Conclusion
This study suggests that both positive CD44v9 and high Ki-67 expression are associated with poor prognosis in EGC, and the combined use of these markers provides better prognostic stratification than the single use of them.

Citations

Citations to this article as recorded by

CD44+ and CD133+ Extracellular Vesicles as Future Potential Targets in Gastrointestinal Tumor
Cristina Pizzulli, Beatrice Menicacci, Margherita Parrini, Edoardo Tonelli, Caterina Bartolini, Armando Curto, Giulia Petroni, Serena Pillozzi, Andrea Galli
Frontiers in Bioscience-Landmark.2026;[Epub] CrossRef
Integration of scRNA-seq and ST-seq identifies hyperproliferative RRM2+ cells features and therapeutic targets in gastric cancer
Shuai Ping, Xiong Jia, Yanan Tian
Journal of Translational Medicine.2025;[Epub] CrossRef
CD44v9 Expression in Pretreatment Biopsies as a Predictor of Chemotherapy Resistance in Gastric Cancer
Katsuji Sawai, Kenji Koneri, Masato Tamaki, Yasuo Hirono, Takanori Goi
Cancers.2025; 17(22): 3657. CrossRef
Development of a nomogram for the prediction of postoperative survival in hepatoid adenocarcinoma of the stomach
Kang Wang, Yusong Chen, Xiaoli Li, Xinshuo Li, Yuqian Zhai, Yudan Yang, Haochen Li, Yan Wang, Ming Gao
Carcinogenesis.2025;[Epub] CrossRef
The Prognostic Importance of Ki-67 in Gastrointestinal Carcinomas: A Meta-analysis and Multi-omics Approach
Mahdieh Razmi, Fatemeh Tajik, Farideh Hashemi, Ayna Yazdanpanah, Fatemeh Hashemi-Niasari, Adeleh Divsalar
Journal of Gastrointestinal Cancer.2024; 55(2): 599. CrossRef
Impact of Alcian blue and periodic acid Schiff expression on the prognosis of gastric signet ring cell carcinoma
Juan Lin, Zhu-Feng Chen, Guo-Dong Guo, Xin Chen
World Journal of Gastrointestinal Oncology.2024; 16(3): 687. CrossRef
Significance of concurrent evaluation of HER2 gene amplification and p53 and Ki67 expression in gastric cancer tissues
Su-nan Wang, Yang-kun Wang, Chao-ya Zhu, Bo Jiang, Dong-feng Ge, Ying-ying Li
Clinical and Translational Oncology.2024; 27(1): 126. CrossRef
Downregulation of MTHFD2 Inhibits Proliferation and Enhances Chemosensitivity in Hepatocellular Carcinoma via PI3K/AKT Pathway
Jie Wang, Ze Yu, Yixiao Jiang, Ting Le, Yixin Wu, Ziqi Li, Guoqiang Zhang, Feiyue Wu, Haijie Ma
Frontiers in Bioscience-Landmark.2024;[Epub] CrossRef
Analysis of risk factors for lymph node metastasis and prognosis study in patients with early gastric cancer: A SEER data-based study
Jinzhou Li, Ting Cui, Zeping Huang, Yanxi Mu, Yalong Yao, Wei Xu, Kang Chen, Haipeng Liu, Wenjie Wang, Xiao Chen
Frontiers in Oncology.2023;[Epub] CrossRef
Revisiting therapeutic strategies for ovarian cancer by focusing on redox homeostasis (Review)
Hiroshi Kobayashi, Shogo Imanaka, Hiroshi Shigetomi
Oncology Letters.2022;[Epub] CrossRef
Cyclin D1 Serves as a Poor Prognostic Biomarker in Stage I Gastric Cancer
Se-Il Go, Gyung Hyuck Ko, Won Sup Lee, Jeong-Hee Lee, Sang-Ho Jeong, Young-Joon Lee, Soon Chan Hong, Woo Song Ha
Current Issues in Molecular Biology.2022; 44(3): 1395. CrossRef
Analysis of Endoscopy Findings to Identify Early Gastric Cancers with Tumor Budding: A Retrospective Study
Lanqing Cao, Zhaoyong Wang, Liwei Duan, Lijuan Wei
Journal of Gastrointestinal Surgery.2021; 25(7): 1706. CrossRef
Clinical significance of circulating tumour cells and Ki-67 in renal cell carcinoma
Jinbo Song, Zhe Yu, Bingqi Dong, Mingkai Zhu, Xiaofeng Guo, Yongkang Ma, Shiming Zhao, Tiejun Yang
World Journal of Surgical Oncology.2021;[Epub] CrossRef
Fascin‑1 is associated with recurrence in solitary fibrous tumor/hemangiopericytoma
Yumiko Yamamoto, Yoshihiro Hayashi, Hideyuki Sakaki, Ichiro Murakami
Molecular and Clinical Oncology.2021;[Epub] CrossRef
Identification of novel biomarkers, MUC5AC, MUC1, KRT7, GAPDH, CD44 for gastric cancer
Jie Yang
Medical Oncology.2020;[Epub] CrossRef
Roles of Proteoglycans and Glycosaminoglycans in Cancer Development and Progression
Jinfen Wei, Meiling Hu, Kaitang Huang, Shudai Lin, Hongli Du
International Journal of Molecular Sciences.2020; 21(17): 5983. CrossRef

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Reduced Expression of E-cadherin in Human Non-small Cell Lung Carcinoma: Na-Hye Myong; Cancer Res Treat. 2004;36(1):56-61. Published online February 29, 2004; DOI: https://doi.org/10.4143/crt.2004.36.1.56

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Purpose

E-cadherin, a calcium-dependent cell to cell adhesion molecule, plays a key role in the maintenance of tissue integrity. Reduction or loss of E-cadherin has been reported to have a role in the development of human malignancies. The expression of E-cadherin was analyzed in human non-small cell lung carcinoma (NSCLC) to elucidate the role in pulmonary carcinogenesis and determine the relationship with several clinicopathological factors and the prognosis.

Materials and Methods

Sixty five human cases of NSCLC were evaluated by immunohistochemical analysis for the expression of E-cadherin. The immunostaining results for E-cadherin were semiquantitatively interpreted, as preserved and reduced, in the tumor tissues. The E-cadherin expression was analyzed in relation to several clinicopathological data and the survival. The cell proliferation index of the tumors was evaluated by immunostaining with the Ki-67 antigen.

Results

Reduced E-cadherin expression was found in 51 cases of NSCLC tissues (78.4%) compared to that in the normal controls. Reduced E-cadherin expression was significantly correlated with male smokers and squamous cell type of the cancer, but not with histological grade, TNM stage and survival. The E-cadherin expression showed a weak inverse relationship with the proliferative activity of tumor cells, which was measured using the Ki-67 antigen.

Conclusion

Our data support the hypothesis that reduced E-cadherin expression may play a role in the pathogenesis of human NSCLC, which might be associated with the control for cell proliferation.

Citations

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