Journal of Pathology and Translational Medicine

Original Articles

Diagnostic value of cytology in detecting human papillomavirus–independent cervical malignancies: a nation-wide study in Korea: Hye-Ra Jung, Junyoung Shin, Chong Woo Yoo, Eun Na Kim, Cheol Lee, Kyeongmin Kim, Ho-chang Lee, Yonghee Lee, Ji Hye Kim, Soo Jin Jung, Yumin Chung, Joo Yeon Kim, Hye Eun Park, Tae Hoen Kim, Wonae Lee, Min-Sun Cho, Ran Hong, Yoon Jung Choi, Younghee Choi, Young Sub Lee, Sang-Ryung Lee, Myunghee Kang, Young Jin Seo, Seung-Sook Lee, Yoon-Jung Hwang, Hyun-Jung Kim; J Pathol Transl Med. 2025;59(6):444-452. Published online November 11, 2025; DOI: https://doi.org/10.4132/jptm.2025.10.21

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Abstract PDF: Background
Human papillomavirus (HPV) independent cervical malignancies (HPV-IDCMs) have recently been classified by the World Health Organization (WHO) 5th edition. These malignancies have historically received limited attention due to their rarity and the potential for evasion of HPV-based screening.
Methods
We retrospectively reviewed 5,854 biopsy-confirmed cervical malignancies from 22 institutions over 3 years (July 2020–June 2023). Histologic classification followed the WHO guidelines. HPV independence was confirmed by dual negativity for p16 and HPV; discordant cases (p16-positive/HPV-negative) underwent additional HPV testing using paraffin-embedded tissue. Cytological results were matched sequentially to histological confirmation.
Results
The prevalence of HPV-IDCM was 4.4% (257/5,854) overall and was 3.6% (208/5,805 cases) among primary cervical malignancy. Patient age of HPV-IDCM was 29 to 89 years (median, 57.79). Its histologic subtypes included primary adenocarcinoma (n = 116), endometrial adenocarcinoma (n = 35), squamous cell carcinoma (n = 72), metastatic carcinoma (n = 14), carcinoma, not otherwise specified (n = 10), neuroendocrine carcinoma (n = 3), and others (n = 7). Among 155 cytology-histological matched cases, the overall and primary Pap test detection rates were 85.2% (132/155) and 83.2% (104/125), respectively. The interval between cytology and histologic confirmation extended up to 38 months.
Conclusions
HPV-IDCMs comprised 3.6% of primary cervical malignancies with a high detection rate via cytology (83.2%). These findings affirm the value of cytological screening, particularly in patients with limited screening history or at risk for HPV-independent lesions, and may guide future screening protocols.

The Smad4/PTEN Expression Pattern Predicts Clinical Outcomes in Colorectal Adenocarcinoma: Yumin Chung, Young Chan Wi, Yeseul Kim, Seong Sik Bang, Jung-Ho Yang, Kiseok Jang, Kyueng-Whan Min, Seung Sam Paik; J Pathol Transl Med. 2018;52(1):37-44. Published online October 23, 2017; DOI: https://doi.org/10.4132/jptm.2017.10.20

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Background
Smad4 and PTEN are prognostic indicators for various tumor types. Smad4 regulates tumor suppression, whereas PTEN inhibits cell proliferation. We analyzed and compared the performance of Smad4 and PTEN for predicting the prognosis of patients with colorectal adenocarcinoma.
Methods
Combined expression patterns based on Smad4+/– and PTEN+/– status were evaluated by immunostaining using a tissue microarray of colorectal adenocarcinoma. The relationships between the protein expression and clinicopathological variables were analyzed.
Results
Smad4–/PTEN– status was most frequently observed in metastatic adenocarcinoma, followed by primary adenocarcinoma and tubular adenoma (p<.001). When Smad4–/PTEN– and Smad4+/PTEN+ groups were compared, Smad4–/PTEN– status was associated with high N stage (p=.018) and defective mismatch repair proteins (p=.006). Significant differences in diseasefree survival and overall survival were observed among the three groups (Smad4+/PTEN+, Smad4–/PTEN+ or Smad4+/PTEN–, and Smad4–/PTEN–) (all p<.05).
Conclusions
Concurrent loss of Smad4 and PTEN may lead to more aggressive disease and poor prognosis in patients with colorectal adenocarcinoma compared to the loss of Smad4 or PTEN alone.

Citations

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Precision oncolytic viral therapy in colorectal cancer: Genetic targeting and immune modulation for personalized treatment (Review)
Muhammad Haris Sultan, Qi Zhan, Yigang Wang, Yulong Xia, Xiaoyuan Jia
International Journal of Molecular Medicine.2025; 56(1): 1. CrossRef
Focal Adhesion Kinase Intersects With the BRD4‐MYC Axis and YAP1 to Drive Tumor Cell Growth, Phenotypic Plasticity, Stemness, and Metastatic Potential in Colorectal Cancer
Rongbo Han, Junfeng Shi, Kai Cheng, Zian Wang, Yecang Chen, Orion Spellecy, Abu Saleh Mosa Faisal, Isha Aryal, Jinfei Chen, Rolf Craven, Olivier Thibault, Lauren Baldwin, Lawrence D. Brewer, Sonia Erfani, Chi Wang, Zhenheng Guo, Eric Chen, Burton Yang, Fr
Cancer Medicine.2025;[Epub] CrossRef
Association between the expression of epithelial–mesenchymal transition (EMT)-related markers and oncologic outcomes of colorectal cancer
Mona Hany Emile, Sameh Hany Emile, Amr Awad El-Karef, Mohamed Awad Ebrahim, Ibrahim Eldosoky Mohammed, Dina Abdallah Ibrahim
Updates in Surgery.2024; 76(6): 2181. CrossRef
The Potential Role of Genomic Signature in Stage II Relapsed Colorectal Cancer (CRC) Patients: A Mono-Institutional Study
Michela Roberto, Giulia Arrivi, Emanuela Pilozzi, Andrea Montori, Genoveffa Balducci, Paolo Mercantini, Andrea Laghi, Debora Ierinò, Martina Panebianco, Daniele Marinelli, Silverio Tomao, Paolo Marchetti, Federica Mazzuca
Cancer Management and Research.2022; Volume 14: 1353. CrossRef
Alterations of PTEN and SMAD4 methylation in diagnosis of breast cancer: implications of methyl II PCR assay
Menha Swellam, Entsar A. Saad, Shimaa Sabry, Adel Denewer, Camelia Abdel Malak, Amr Abouzid
Journal of Genetic Engineering and Biotechnology.2021; 19(1): 54. CrossRef
E3 ubiquitin ligase HECW1 promotes the metastasis of non-small cell lung cancer cells through mediating the ubiquitination of Smad4
Chen Lu, Guangyao Ning, Panpan Si, Chunsheng Zhang, Wenjian Liu, Wei Ge, Kai Cui, Renquan Zhang, Shenglin Ge
Biochemistry and Cell Biology.2021; 99(5): 675. CrossRef
Computational quantification of global effects induced by mutations and drugs in signaling networks of colorectal cancer cells
Sara Sommariva, Giacomo Caviglia, Silvia Ravera, Francesco Frassoni, Federico Benvenuto, Lorenzo Tortolina, Nicoletta Castagnino, Silvio Parodi, Michele Piana
Scientific Reports.2021;[Epub] CrossRef
Clinicopathological characterization of SMAD4-mutated intestinal adenocarcinomas: A case-control study
Xiaoyan Liao, Yansheng Hao, Xiaofei Zhang, Stephen Ward, Jane Houldsworth, Alexandros D. Polydorides, Noam Harpaz, Aldo Scarpa
PLOS ONE.2019; 14(2): e0212142. CrossRef
Clinicopathological Characterization and Prognostic Implication of SMAD4 Expression in Colorectal Carcinoma
Seung-Yeon Yoo, Ji-Ae Lee, Yunjoo Shin, Nam-Yun Cho, Jeong Mo Bae, Gyeong Hoon Kang
Journal of Pathology and Translational Medicine.2019; 53(5): 289. CrossRef
Dissecting the therapeutic implications of the complex SMAD4 regulatory network in metastatic colorectal cancer
Ion Cristóbal, Blanca Torrejón, Andrea Santos, Melani Luque, Marta Sanz-Alvarez, Federico Rojo, Jesús García-Foncillas
European Journal of Surgical Oncology.2018; 44(8): 1283. CrossRef
Reply to: Dissecting the therapeutic implications of the complex SMAD4 regulatory network in metastatic colorectal cancer
Jordan M. Cloyd, Takashi Mizuno, Jean-Nicolas Vauthey
European Journal of Surgical Oncology.2018; 44(8): 1285. CrossRef

Clinicopathologic Correlations of E-cadherin and Prrx-1 Expression Loss in Hepatocellular Carcinoma: Kijong Yi, Hyunsung Kim, Yumin Chung, Hyein Ahn, Jongmin Sim, Young Chan Wi, Ju Yeon Pyo, Young-Soo Song, Seung Sam Paik, Young-Ha Oh; J Pathol Transl Med. 2016;50(5):327-336. Published online August 31, 2016; DOI: https://doi.org/10.4132/jptm.2016.06.22

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Abstract PDF

Background
Developing predictive markers for hepatocellular carcinoma (HCC) is important, because many patients experience recurrence and metastasis. Epithelial to mesenchymal transition (EMT) is a developmental process that plays an important role during embryogenesis and also during cancer metastasis. Paired-related homeobox protein 1 (Prrx-1) is an EMT inducer that has recently been introduced, and its prognostic significance in HCC is largely unknown.
Methods
Tissue microarray was constructed using surgically resected primary HCCs from 244 cases. Immunohistochemical staining of E-cadherin and Prrx-1 was performed. The correlation between E-cadherin loss and Prrx-1 expression, as well as other clinicopathologic factors, was evaluated.
Results
E-cadherin expression was decreased in 96 cases (39.4%). Loss of E-cadherin correlated with a higher recurrence rate (p < .001) but was not correlated with patient’s survival. Thirty-two cases (13.3%) showed at least focal nuclear Prrx-1 immunoreactivity while all non-neoplastic livers (n = 22) were negative. Prrx-1 expression was not associated with E-cadherin loss, survival or recurrence rates, pathologic factors, or the Ki-67 labeling index. Twenty tumors that were positive for E-cadherin and Prrx-1 had significantly higher nuclear grades than the rest of the cohort (p = .037). In Cox proportional hazard models, E-cadherin loss and large vessel invasion were independent prognostic factors for shorter disease-free survival. Cirrhosis and high Ki-67 index (> 40%) were independent prognostic factors for shorter overall survival.
Conclusions
Prrx-1 was expressed in small portions of HCCs but not in normal livers. Additional studies with a large number of Prrx-1-positive cases are required to confirm the results of this study.

Citations

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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
Homotypic cell-in-cell structures as an adverse prognostic predictor of hepatocellular carcinoma
Ruizhi Wang, Yichao Zhu, Hao Zhong, Xinyue Gao, Qiang Sun, Meifang He
Frontiers in Oncology.2022;[Epub] CrossRef
Dysregulated paired related homeobox 1 impacts on hepatocellular carcinoma phenotypes
Weronika Piorońska, Zeribe Chike Nwosu, Mei Han, Michael Büttner, Matthias Philip Ebert, Steven Dooley, Christoph Meyer
BMC Cancer.2021;[Epub] CrossRef

Brief Case Reports

Pelvic Nodular Histiocytic and Mesothelial Hyperplasia in a Patient with Endometriosis and Uterine Leiomyoma: Yumin Chung, Rehman Abdul, Se Min Jang, Joong Sub Choi, Kiseok Jang; J Pathol Transl Med. 2016;50(5):397-400. Published online April 4, 2016; DOI: https://doi.org/10.4132/jptm.2016.01.11

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Nodular Histiocytic Aggregates of the Greater Omentum Mimicking Peritoneal Carcinomatosis on Imaging
Nada Elmukhtar, Jawad Al-Khalaf, Ali Alsehaiw, Lobaina Abozaid
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Papillary Histiocytic and Mesothelial Hyperplasia of the Ovary Related to a Huge Uterus: A Case Report
Kyeoungseo Park, Kyeongmin Kim, Yon Hee Kim, Yoon Mee Jeen, Dong Won Kim, So-Young Jin, In Ho Choi
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Lymphoepithelioma-like Carcinoma of the Renal Pelvis: A Case Report and Review of the Literature: Hyein Ahn, Jongmin Sim, Hyunsung Kim, Kijong Yi, Hulin Han, Yumin Chung, Abdul Rehman, Seung Sam Paik; Korean J Pathol. 2014;48(6):458-461. Published online December 31, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.6.458

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