Journal of Pathology and Translational Medicine

Original Articles

MicroRNA-552 expression in colorectal cancer and its clinicopathological significance: Joon Im, Soo Kyung Nam, Hye Seung Lee; J Pathol Transl Med. 2021;55(2):125-131. Published online February 19, 2021; DOI: https://doi.org/10.4132/jptm.2021.01.17

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Background
MicroRNA-552 (miR-552) has been reported to correlate with the development and progression of various cancers, including colorectal cancer (CRC). This study aimed to investigate miR-552 expression in cancer tissue samples compared to normal mucosal tissue and its role as a diagnostic or prognostic marker in CRC patients.
Methods
Normal mucosal tissues and primary cancer tissues from 80 surgically resected CRC specimens were used. Quantitative real-time polymerase chain reaction was performed for miR-552 and U6 small nuclear RNA to analyze miR-552 expression and its clinicopathological significance. Immunohistochemistry for p53 and phosphatase and tension homolog (PTEN) was performed to evaluate their association with miR-552 expression.
Results
miR-552 expression was significantly higher in primary cancer tissues compared to normal mucosal tissues (p<.001). The expression level of miR552 was inversely correlated with that of PTEN (p=.068) and p53 (p=.004). Survival analysis showed that high miR-552 expression was associated with worse prognosis but this was not statistically significant (p=.255). However, patients with CRC having high miR-552 expression and loss of PTEN expression had significantly worse prognosis than others (p=.029).
Conclusions
Our results suggest that high miR-552 expression might be a potential diagnostic biomarker for CRC, and its combined analysis with PTEN expression can possibly be used as a prognostic marker.

Citations

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Blood miRNAs miR-549a, miR-552, and miR-592 serve as potential disease-specific panels to diagnose colorectal cancer
Soroush Akbar, Samaneh Mashreghi, Mohammad Reza Kalani, Akram Valanik, Farzaneh Ahmadi, Mahdi Aalikhani, Zahra Bazi
Heliyon.2024; 10(7): e28492. CrossRef
Integration of TE Induces Cancer Specific Alternative Splicing Events
Woo Ryung Kim, Eun Gyung Park, Yun Ju Lee, Woo Hyeon Bae, Du Hyeong Lee, Heui-Soo Kim
International Journal of Molecular Sciences.2022; 23(18): 10918. CrossRef

Prediction of TP53 mutations by p53 immunohistochemistry and their prognostic significance in gastric cancer: Hye Jung Hwang, Soo Kyung Nam, Hyunjin Park, Yujun Park, Jiwon Koh, Hee Young Na, Yoonjin Kwak, Woo Ho Kim, Hye Seung Lee; J Pathol Transl Med. 2020;54(5):378-386. Published online July 1, 2020; DOI: https://doi.org/10.4132/jptm.2020.06.01

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Abstract PDF Supplementary Material

Background
Recently, molecular classifications of gastric cancer (GC) have been proposed that include TP53 mutations and their functional activity. We aimed to demonstrate the correlation between p53 immunohistochemistry (IHC) and TP53 mutations as well as their clinicopathological significance in GC.
Methods
Deep targeted sequencing was performed using surgical or biopsy specimens from 120 patients with GC. IHC for p53 was performed and interpreted as strong, weak, or negative expression. In 18 cases (15.0%) with discrepant TP53 mutation and p53 IHC results, p53 IHC was repeated.
Results
Strong expression of p53 was associated with TP53 missense mutations, negative expression with other types of mutations, and weak expression with wild-type TP53 (p<.001). The sensitivity for each category was 90.9%, 79.0%, and 80.9%, and the specificity was 95.4%, 88.1%, and 92.3%, respectively. The TNM stage at initial diagnosis exhibited a significant correlation with both TP53 mutation type (p=.004) and p53 expression status (p=.029). The Kaplan-Meier survival analysis for 109 stage II and III GC cases showed that patients with TP53 missense mutations had worse overall survival than those in the wild-type and other mutation groups (p=.028). Strong expression of p53 was also associated with worse overall survival in comparison to negative and weak expression (p=.035).
Conclusions
Results of IHC of the p53 protein may be used as a simple surrogate marker of TP53 mutations. However, negative expression of p53 and other types of mutations of TP53 should be carefully interpreted because of its lower sensitivity and different prognostic implications.

Citations

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Hae Young Kim, Won Chang, Yoon Jin Lee, Ji Hoon Park, Jungheum Cho, Hee Young Na, Hyungwoo Ahn, Sung Il Hwang, Hak Jong Lee, Young Hoon Kim, Kyoung Ho Lee
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World Journal of Clinical Oncology.2022; 13(10): 762. CrossRef
MicroRNA-552 expression in colorectal cancer and its clinicopathological significance
Joon Im, Soo Kyung Nam, Hye Seung Lee
Journal of Pathology and Translational Medicine.2021; 55(2): 125. CrossRef
Different effects of p53 protein overexpression on the survival of gastric cancer patients according to Lauren histologic classification: a retrospective study
Ki Wook Kim, Nayoung Kim, Yonghoon Choi, Won Seok Kim, Hyuk Yoon, Cheol Min Shin, Young Soo Park, Dong Ho Lee, Young Suk Park, Sang-Hoon Ahn, Do Joong Park, Hyung-Ho Kim, Hye Seung Lee, Ji-Won Kim, Jin Won Kim, Keun-Wook Lee, Won Chang, Ji Hoon Park, Yoon
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Molecular and Clinicopathological Features of Gastrointestinal Stromal Tumors in Vietnamese Patients: Quoc Dat Ngo, Quoc Thang Pham, Dang Anh Thu Phan, Anh Vu Hoang, Thi Ngoc Ha Hua, Sao Trung Nguyen; J Pathol Transl Med. 2019;53(6):361-368. Published online September 16, 2019; DOI: https://doi.org/10.4132/jptm.2019.08.27

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Abstract PDF Supplementary Material

Background
Gastrointestinal stromal tumors (GISTs) are the most frequent mesenchymal neoplasms of the gastrointestinal tract. Management of GIST patients is currently based on clinicopathological features and associated genetic changes. However, the detailed characteristics and molecular genetic features of GISTs have not yet been described in the Vietnamese population.
Methods
We first identified 155 patients with primary GIST who underwent surgery with primary curative intent between 2011 and 2014 at University Medical Center at Ho Chi Minh City, Vietnam. We evaluated the clinicopathological features and immunohistochemical reactivity to p53 and Ki-67 in these patients. Additionally, KIT genotyping was performed in 100 cases.
Results
The largest proportion of GISTs was classified as high-risk (43.2%). Of the 155 GISTs, 52 (33.5%) were positive for Ki-67, and 58 (37.4%) were positive for p53. The expression of Ki-67 and p53 were correlated with mitotic rate, tumor size, risk assessment, and tumor stage. Out of 100 GIST cases, KIT mutation was found in 68%, of which 62 (91.2%) were found in exon 11, two (2.9%) in exon 9, and four (5.8%) in exon 17. No mutation in exon 13 was identified. Additionally, KIT mutations did not correlate with any clinicopathological features.
Conclusions
The expression of Ki-67 and p53 were associated with high-risk tumors. Mutations in exon 11 were the most commonly found, followed by exon 17 and exon 9. Additionally, KIT mutation status was not correlated with any recognized clinicopathological features.

Citations

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Ki67 for evaluating the prognosis of gastrointestinal stromal tumors: A systematic review and meta‑analysis
Ji Li, An-Ran Wang, Xiao-Dong Chen, Hong Pan, Shi-Qiang Li
Oncology Letters.2022;[Epub] CrossRef
Endoscopic ultrasound‐guided fine‐needle aspiration cytology in the diagnosis of the gastrointestinal stromal tumor of the stomach
José‐Fernando Val‐Bernal, Elena Yllera, María Moris, Ihab Abdulkader Nallib, Angel Vázquez‐Boquete, María Martino
Diagnostic Cytopathology.2020; 48(9): 833. CrossRef

Serous Adenocarcinoma of Fallopian Tubes: Histological and Immunohistochemical Aspects: Natalia Hyriavenko, Mykola Lyndin, Kateryna Sikora, Artem Piddubnyi, Ludmila Karpenko, Olha Kravtsova, Dmytrii Hyriavenko, Olena Diachenko, Vladyslav Sikora, Anatolii Romaniuk; J Pathol Transl Med. 2019;53(4):236-243. Published online April 11, 2019; DOI: https://doi.org/10.4132/jptm.2019.03.21

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Abstract PDF

Background
Although primary cancer of the fallopian tubes is a relatively rare type of tumor in female reproductive organs, its mortality is quite high. It is important to identify molecular and biological markers of this malignancy that determine its specific phenotype.
Methods
The study was carried out on samples received from 71 female patients with primary cancer of the fallopian tubes. The main molecular and biological properties, including hormone status (estrogen receptor [ER], progesterone receptor [PR]), human epidermal growth factor receptor (HER2)/neu expression, proliferative potential (Ki-67), apoptosis (p53, Bcl-2), and pro-angiogenic (vascular endothelial growth factor) quality of serous tumors were studied in comparison with clinical and morphological characteristics.
Results
ER and PR expression is accompanied by low grade neoplasia, early clinical disease stage, and absence of lymphogenic metastasis (p < .001). HER2/neu expression is not typical for primary cancer of the fallopian tubes. Ki-67 expression is characterized by an inverse correlation with ER and PR (p < .05) and is associated with lymphogenic metastasis (p < .01). p53+ status correlates with high grade malignancy, tumor progression, metastasis, negative ER/PR (p < .001), and negative Bcl-2 status (p < .05). Positive Bcl-2 status is positively correlated with ER and PR expression and low grade malignancy.
Conclusions
Complex morphologic (histological and immunohistochemical) study of postoperative material allows estimation of the degree of malignancy and tumor spread to enable appropriate treatment for each case.

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Rare non-serous fallopian tube cancers: institutional experience and literature review
Dmitrii Sumtsov, Georgyi Sumtsov, Nataliia Hyriavenko, Mykola Lyndin, Kateryna Sikora, Nataliia Kalashnik, Svitlana Smiian, Igor Gladchuk
Wiener Medizinische Wochenschrift.2024; 174(9-10): 199. CrossRef
UŞAQLIQ BORULARININ BİRİNCİLİ XƏRÇƏNGİ: DİAQNOSTİKASI VƏ MÜALİCƏSİNİN NƏTİCƏLƏRİ
D.G. Sumtsov, G.O. Sumtsov, N.I. Hyriavenko, S.A. Smiian, N.V. Kalashnyk, K.O. Sikora, N.M. Rozhkovska, I.Z. Gladchuk
Azerbaijan Medical Journal.2023; (4): 75. CrossRef
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M. Lytvynenko
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Mandy Womble, Megan E. Schreeg, Allison Hoch, Enoch B. de Souza Meira, Derek Foster, Christopher Premanandan, Tatiane T. Negrão Watanabe
Journal of Comparative Pathology.2021; 189: 52. CrossRef
Problems of primary fallopian tube cancer diagnostics during and after surgery
D.G. Sumtsov, I.Z. Gladchuk, G.O. Sumtsov, N.I. Hyriavenko, M.S. Lyndin, V.V. Sikora, V.M. Zaporozhan
REPRODUCTIVE ENDOCRINOLOGY.2021; (59): 66. CrossRef

Association between Expression of 8-OHdG and Cigarette Smoking in Non-small Cell Lung Cancer: Ae Ri An, Kyoung Min Kim, Ho Sung Park, Kyu Yun Jang, Woo Sung Moon, Myoung Jae Kang, Yong Chul Lee, Jong Hun Kim, Han Jung Chae, Myoung Ja Chung; J Pathol Transl Med. 2019;53(4):217-224. Published online March 11, 2019; DOI: https://doi.org/10.4132/jptm.2019.02.20

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Abstract PDF

Background
Exposure to cigarette smoking (CS) is a major risk factor for the development of lung cancer. CS is known to cause oxidative DNA damage and mutation of tumor-related genes, and these factors are involved in carcinogenesis. 8-Hydroxydeoxyguanosine (8-OHdG) is considered to be a reliable biomarker for oxidative DNA damage. Increased levels of 8-OHdG are associated with a number of pathological conditions, including cancer. There are no reports on the expression of 8-OHdG by immunohistochemistry in non-small cell lung cancer (NSCLC).
Methods
We investigated the expression of 8-OHdG and p53 in 203 NSCLC tissues using immunohistochemistry and correlated it with clinicopathological features including smoking.
Results
The expression of 8-OHdG was observed in 83.3% of NSCLC. It was significantly correlated with a low T category, negative lymph node status, never-smoker, and longer overall survival (p < .05) by univariate analysis. But multivariate analysis revealed that 8-OHdG was not an independent prognostic factor for overall survival in NSCLC patients. The aberrant expression of p53 significantly correlated with smoking, male, squamous cell carcinoma, and Ki-67 positivity (p < .05).
Conclusions
The expression of 8-OHdG was associated with good prognostic factors. It was positively correlated with never-smokers in NSCLC, suggesting that oxidative damage of DNA cannot be explained by smoking alone and may depend on complex control mechanisms.

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Association between p53 Expression and Amount of Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer: Miseon Lee, In Ah Park, Sun-Hee Heo, Young-Ae Kim, Gyungyub Gong, Hee Jin Lee; J Pathol Transl Med. 2019;53(3):180-187. Published online March 11, 2019; DOI: https://doi.org/10.4132/jptm.2019.02.08

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Abstract PDF

Background
Most triple-negative breast cancers (TNBCs) have a high histologic grade, are associated with high endoplasmic stress, and possess a high frequency of TP53 mutations. TP53 missense mutations lead to the production of mutant p53 protein and usually show high levels of p53 protein expression. Tumor-infiltrating lymphocytes (TILs) accumulate as part of the anti-tumor immune response and have a strong prognostic and predictive significance in TNBC. We aimed to elucidate the association between p53 expression and the amount of TILs in TNBC.
Methods
In 678 TNBC patients, we evaluated TIL levels and expression of endoplasmic stress molecules. Immunohistochemical examination of p53 protein expression was categorized into three groups: no, low, and high expression.
Results
No, low, and high p53 expression was identified in 44.1% (n = 299), 20.1% (n = 136), and 35.8% (n = 243) of patients, respectively. Patients with high p53 expression showed high histologic grade (p < .001), high TIL levels (p = .009), and high expression of endoplasmic reticulum stress-associated molecules (p-eIF2a, p = .013; XBP1, p = .007), compared to patients with low p53 expression. There was no significant difference in disease-free (p = .406) or overall survival rates (p = .444) among the three p53 expression groups.
Conclusions
High p53 expression is associated with increased expression of endoplasmic reticulum stress molecules and TIL influx.

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Koen Brummel, Anneke L. Eerkens, Marco de Bruyn, Hans W. Nijman
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Dihydroartemisinin-Transferrin Adducts Enhance TRAIL-Induced Apoptosis in Triple-Negative Breast Cancer in a P53-Independent and ROS-Dependent Manner
Xinyu Zhou, Abel Soto-Gamez, Fleur Nijdam, Rita Setroikromo, Wim J. Quax
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Uterine Malignant Mixed Müllerian Tumors Following Treatment with Selective Estrogen Receptor Modulators in Patients with Breast Cancer: A Report of 13 Cases and Their Clinicopathologic Characteristics: Byung-Kwan Jeong, Chang O. Sung, Kyu-Rae Kim; J Pathol Transl Med. 2019;53(1):31-39. Published online December 18, 2018; DOI: https://doi.org/10.4132/jptm.2018.11.16

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Abstract PDF

Background
Breast cancer treatment with selective estrogen receptor modulators (SERMs) increasesthe incidence of uterine malignant mixed Müllerian tumors (uMMMTs). We examine clinicopathologiccharacteristics and prognosis of SERM-associated uMMMTs (S-uMMMTs) and discusspossible pathogenetic mechanisms.
Methods
Among 28,104 patients with breast cancer, clinicopathologicfeatures and incidence of uMMMT were compared between patients who underwentSERM treatment and those who did not. Of 92 uMMMT cases that occurred during the same period,incidence, dose, and duration of SERM treatment, as well as overall survival rate, were comparedfor patients with breast cancer who underwent SERM treatment and those who did not (S-uMMMTvs NS-uMMMT) and for patients without breast cancer (de novo-uMMMT). Histopathologicalfindings and immunophenotypes for myogenin, desmin, p53, WT-1, estrogen receptor (ER) α, ERβ,progesterone receptor, and GATA-3 were compared between S-uMMMT and de novo-uMMMT.
Results
The incidence of S-uMMMT was significantly higher than that of NS-uMMMT (6.35-fold).All patients with SERM were postmenopausal and received daily 20–40 mg SERM. CumulativeSERM dose ranged from 21.9 to 73.0 g (mean, 46.0) over 39–192 months (mean, 107). Clinicopathologicfeatures, such as International Federation of Gynecology and Obstetrics stage andoverall survival, were not significantly different between patients with S-uMMMT and NS-uMMMTor between patients with S-uMMMT and de novo-uMMMT. All 11 S-uMMMT cases available forimmunostaining exhibited strong overexpression/null expression of p53 protein and significantlyincreased ERβ expression in carcinomatous and sarcomatous components.
Conclusions
SERMtherapy seemingly increases risk of S-uMMMT development; however, clinicopathologic featureswere similar in all uMMMTs from different backgrounds. p53 mutation and increased ERβ expressionmight be involved in the etiology of S-uMMMT.

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Basaloid Squamous Cell Carcinoma of the Head and Neck: Subclassification into Basal, Ductal, and Mixed Subtypes Based on Comparison of Clinico-pathologic Features and Expression of p53, Cyclin D1, Epidermal Growth Factor Receptor, p16, and Human Papillomavirus: Kyung-Ja Cho, Se Un Jeong, Sung Bae Kim, Sang-wook Lee, Seung-Ho Choi, Soon Yuhl Nam, Sang Yoon Kim; J Pathol Transl Med. 2017;51(4):374-380. Published online June 8, 2017; DOI: https://doi.org/10.4132/jptm.2017.03.03

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Abstract PDF

Background
Basaloid squamous cell carcinoma (BSCC) is a rare variant of squamous cell carcinoma with distinct pathologic characteristics. The histogenesis of BSCC is not fully understood, and the cancer has been suggested to originate from a totipotent primitive cell in the basal cell layer of the surface epithelium or in the proximal duct of secretory glands.
Methods
Twenty-six cases of head and neck BSCC from Asan Medical Center, Seoul, Korea, reported during a 14-year-period were subclassified into basal, ductal, and mixed subtypes according to the expression of basal (cytokeratin [CK] 5/6, p63) or ductal markers (CK7, CK8/18). The cases were also subject to immunohistochemical study for CK19, p53, cyclin D1, epidermal growth factor receptor (EGFR), and p16 and to in situ hybridization for human papillomavirus (HPV), and the results were clinico-pathologically compared.
Results
Mixed subtype (12 cases) was the most common, and these cases showed hypopharyngeal predilection, older age, and higher expression of CK19, p53, and EGFR than other subtypes. The basal subtype (nine cases) showed frequent comedo-necrosis and high expression of cyclin D1. The ductal subtype (five cases) showed the lowest expression of p53, cyclin D1, and EGFR. A small number of p16- and/or HPV-positive cases were not restricted to one subtype. BSCC was the cause of death in 19 patients, and the average follow-up period for all patients was 79.5 months. Overall survival among the three subtypes was not significantly different.
Conclusions
The results of this study suggest a heterogeneous pathogenesis of head and neck BSCC. Each subtype showed variable histology and immunoprofiles, although the clinical implication of heterogeneity was not determined in this study.

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HPV-associated oropharyngeal cancer: epidemiology, molecular biology and clinical management
Matt Lechner, Jacklyn Liu, Liam Masterson, Tim R. Fenton
Nature Reviews Clinical Oncology.2022; 19(5): 306. CrossRef
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Yinghong Zhang, Suqing Tian, Yali Du, Qiang Zuo, Li Zhu, Furong Ma
Medicine: Case Reports and Study Protocols.2022; 3(6): e0044. CrossRef
Cetuximab and paclitaxel combination therapy for recurrent basaloid squamous cell carcinoma in the ethmoid sinus
Satoshi Koyama, Kazunori Fujiwara, Tsuyoshi Morisaki, Taihei Fujii, Yosuke Nakamura, Takahiro Fukuhara, Hiromi Takeuchi
Auris Nasus Larynx.2021; 48(6): 1189. CrossRef
Constitutive Hedgehog/GLI2 signaling drives extracutaneous basaloid squamous cell carcinoma development and bone remodeling
Marina Grachtchouk, Jianhong Liu, Mark E Hutchin, Paul W Harms, Dafydd Thomas, Lebing Wei, Aiqin Wang, Donelle Cummings, Lori Lowe, Jonathan Garlick, James Sciubba, Arul M Chinnaiyan, Monique E Verhaegen, Andrzej A Dlugosz
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Conjunctival ‘mucoepidermoid carcinoma’ revisited: a revision of terminology, based on morphologic, immunohistochemical and molecular findings of 14 cases, and the 2018 WHO Classification of Tumours of the Eye
Hardeep S. Mudhar, Tatyana Milman, Paul J.L. Zhang, Carol L. Shields, Ralph C. Eagle, Sara E. Lally, Jerry A. Shields, Sachin M. Salvi, Paul A. Rundle, Jennifer Tan, Ian G. Rennie
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Basaloid squamous cell carcinoma with adenoid cystic‐like features of the head and neck region: A report of two cases
Kimihide Kusafuka, Haruna Yagi, Satoshi Baba, Hiroshi Inagaki, Chinatsu Tsuchiya, Kazuki Hirata, Aya Muramatsu, Makoto Suzuki, Kazumori Arai, Tadashi Terada
Pathology International.2020; 70(10): 767. CrossRef
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Lifang Cui, Congling Qu, Honggang Liu
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Linxiu Liu, Xuemin Xue, Liyan Xue
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Jun-Sang Lee, Uk-Kyu Kim, Dae-Seok Hwang, Jun-Ho Lee, Hong-Seok Choi, Na-Rae Choi, Mi Heon Ryu, Gyoo Cheon Kim
The Korean Journal of Oral and Maxillofacial Pathology.2019; 43(5): 197. CrossRef
p53 and p16 expression in oral cavity squamous cell and basaloid squamous cell carcinoma
Allisson Filipe Lopes Martins, Carlos Henrique Pereira, Marília Oliveira Morais, Paulo Otávio Carmo Souza, Lucas Borges Fleury Fernandes, Aline Carvalho Batista, Elismauro Francisco Mendonça
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The Predictive Value of Pathologic Features in Pituitary Adenoma and Correlation with Pituitary Adenoma Recurrence: Jee Soon Kim, Youn Soo Lee, Min Jung Jung, Yong Kil Hong; J Pathol Transl Med. 2016;50(6):419-425. Published online October 6, 2016; DOI: https://doi.org/10.4132/jptm.2016.06.30

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Abstract PDF

Background
The 2004 World Health Organization classification introduced atypical pituitary adenoma (aPA), which was equivocally defined as invasion with increased mitotic activity that had a Ki-67 labeling index (LI) greater than 3%, and extensive p53 immunoreactivity. However, aPAs that exhibit all of these features are rare and the predictive value for recurrence in pituitary adenomas (PAs) remains uncertain. Thus, we sought to characterize pathological features of PAs that correlated with recurrence.
Methods
One hundred and sixty-seven cases of surgically resected PA or aPA were retrieved from 2011 to 2013 in Seoul St. Mary’s Hospital. Among them, 28 cases were confirmed to be recurrent, based on pathologic or radiologic examination. The pathologic characteristics including mitosis, invasion, Ki-67 LI and p53 immunoreactivity were analyzed in relation to recurrence.
Results
Analysis of the pathologic features indicated that only Ki-67 LI over 3% was significantly associated with tumor recurrence (p = .02). The cases with at least one pathologic feature showed significantly higher recurrence rates (p < .01). Analysis indicated that cases with two pathologic features, Ki-67 LI over 3% and extensive p53 immunoreactivity 20% or more, were significantly associated with tumor recurrence (p < .01).
Conclusions
Based on these results, PA tumor recurrence can be predicted by using mitosis, invasion, Ki-67 LI (3%), or extensive p53 immunoreactivity (≥ 20%). Assessment of these features is recommended for PA diagnosis for more accurate prediction of recurrence.

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E. Guadagno, E. D’Avella, P. Cappabianca, A. Colao, M. Del Basso De Caro
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The Role of TWIST in Ovarian Epithelial Cancers: Kyungbin Kim, Eun Young Park, Man Soo Yoon, Dong Soo Suh, Ki Hyung Kim, Jeong Hee Lee, Dong Hoon Shin, Jee Yeon Kim, Mee Young Sol, Kyung Un Choi; Korean J Pathol. 2014;48(4):283-291. Published online August 26, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.4.283

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Abstract PDF

Background

Epithelial-mesenchymal transition (EMT) is associated with tumor hypoxia. EMT is regulated, in part, by the action of TWIST, which inhibits of E-cadherin expression and may interfere with the p53 tumor-suppressor pathway.

Methods

We examined the expression of TWIST, E-cadherin, hypoxia-inducible factor 1α (HIF1α), and p53 by immunohistochemistry in 123 cases of ovarian epithelial cancers (OEC) to evaluate the role of TWIST in OEC. We assessed the association between protein expression and clinicopathologic parameters.

Results

The expression of TWIST, E-cadherin, HIF1α, and p53 proteins was found in 28.5%, 51.2%, 35.0%, and 29.3% of cases, respectively. TWIST expression was associated with higher histologic grade and unfavorable survival. TWIST expression was correlated with HIF1α expression and reduced E-cadherin expression. The altered HIF1α/TWIST/E-cadherin pathway was associated with lower overall survival (OS), while the co-expression of TWIST and p53 was correlated with lower progression-free survival. In the multivariate analyses, TWIST expression was an independent prognostic factor for OS.

Conclusions

Our data imply that TWIST expression could be a useful predictor of unfavorable prognosis for OEC. TWIST may affect the p53 tumor-suppressor pathway. Moreover, hypoxia-mediated EMT, which involves the HIF1α/TWIST/E-cadherin pathway may play an important role in the progression of OEC.

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Michal Kielbik, Izabela Szulc-Kielbik, Magdalena Klink
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Danchen Wu, Asish Dasgupta, Austin D. Read, Rachel E.T. Bentley, Mehras Motamed, Kuang-Hueih Chen, Ruaa Al-Qazazi, Jeffrey D. Mewburn, Kimberly J. Dunham-Snary, Elahe Alizadeh, Lian Tian, Stephen L. Archer
Free Radical Biology and Medicine.2021; 170: 150. CrossRef
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Shing Yau Tam, Vincent W. C. Wu, Helen K. W. Law
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Expression of selected epithelial–mesenchymal transition transcription factors in serous borderline ovarian tumors and type I ovarian cancers
Pawel Sadlecki, Jakub Jóźwicki, Paulina Antosik, Marek Grabiec
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Expression and prognostic significance of epithelial-mesenchymal transition-related markers and phenotype in serous ovarian cancer
In Hye Song, Kyu-Rae Kim, Sehun Lim, Seok-Hyung Kim, Chang Ohk Sung
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Transcription factors controlling E-cadherin down-regulation in ovarian cancer
Holly Russell, Md Zahidul Islam Pranjol
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Maryam Seyedmajidi, Safoura Seifi, Dariush Moslemi, Seyyedeh-Fatemeh Mozaffari, Hemmat Gholinia, Zahra Zolfaghari
Journal of Cancer Research and Therapeutics.2018; 14(5): 964. CrossRef
Activation of TWIST1 by COL11A1 promotes chemoresistance and inhibits apoptosis in ovarian cancer cells by modulating NF‐κB‐mediated IKKβ expression
Yi‐Hui Wu, Yu‐Fang Huang, Tzu‐Hao Chang, Cheng‐Yang Chou
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MicroRNA-219-5p inhibits the proliferation, migration, and invasion of epithelial ovarian cancer cells by targeting the Twist/Wnt/β-catenin signaling pathway
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IMP3, a Promising Prognostic Marker in Clear Cell Renal Cell Carcinoma: Ji Young Park, Misun Choe, Yuna Kang, Sang Sook Lee; Korean J Pathol. 2014;48(2):108-116. Published online April 28, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.2.108

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Abstract PDF

Background

Insulin-like growth factor II mRNA-binding protein 3 (IMP3) has been reported as a prognostic biomarker in various cancers. To validate IMP3 as a prognostic biomarker in renal cell carcinoma (RCC), we investigated the expression of IMP3, p53, and Ki-67, and their associations with clinicopathologic outcomes.

Methods

We studied 148 clear cell RCCs (CCRCCs) from patients who underwent radical nephrectomy. The expression levels of IMP3, p53, and Ki-67 were assessed by immunohistochemical staining and the clinical and pathologic parameters were retrospectively reviewed.

Results

Twenty-nine percent of CCRCCs expressed IMP3. Forty-one percent of IMP3-immunopositive tumors developed metastases, while only 11.4% of IMP3-negative tumors developed metastases (p<.001). A Kaplan-Meier curve showed that patients with IMP3-immunopositive tumors had lower metastasis-free survival and cancer-specific survival than did those with IMP3-immunonegative tumors (p<.001 and p<.001, respectively). Expression of high Ki-67 proliferation index was also associated with a higher metastatic rate. In the multivariate Cox regression analysis, pT stage and IMP3-positivity were independently associated with disease-specific survival.

Conclusions

IMP3 is an independent prognostic biomarker for patients with CCRCC to predict metastasis and poor outcome.

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Shuping You, Yun Guan, Weihong Li
Molecular Medicine Reports.2017;[Epub] CrossRef

Distribution of Human Papillomavirus 52 and 58 Genotypes, and Their Expression of p16 and p53 in Cervical Neoplasia: Tae Eun Kim, Hwal Woong Kim, Kyung Eun Lee; Korean J Pathol. 2014;48(1):24-29. Published online February 25, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.1.24

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Abstract PDF

Background

This study investigates the prevalence of human papillomavirus (HPV) 52 and 58 genotypes among women residing in Busan, and the expression of p16 and p53 proteins in cervical neoplasia with HPV 52 and 58 infections.

Methods

A total of three hundred fifteen cases were analyzed using the HPV DNA chip test for HPV genotypes, and of these, we retrospectively examined p16 and p53 expression in 62 cases of cervical tissues infected with HPV 52 and 58 using immunohistochemistry.

Results

HPV 52 and 58 genotypes were identified in 62 (54.9%) out of 113 high-risk, HPV-infected cases. Of the cases examined, there were 19 single HPV 52 infections (16.8%), 23 single HPV 58 infections (20.4%), 4 multiple HPV 52 infections (3.5%), and 16 multiple HPV-58 infections (14.2%). Immunoreactivity of p16 and p53 was observed in 41 (66.1%) and 23 (37.1%) of the 62 cases of cervical neoplasia infected with HPV 52 and 58 genotypes, respectively.

Conclusions

This study demonstrates a high prevalence of HPV 52 and 58 genotypes, in addition to HPV 16, among high-risk strains of cervical neoplasia in Korea. These findings suggest that development of more vaccines would be beneficial for the prevention of the various HPV genotypes.

Citations

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Screening for High-Risk Human Papillomavirus Reveals HPV52 and HPV58 among Pediatric and Adult Patient Saliva Samples
Hunter Hinton, Lorena Herrera, Sofia Valenzuela, Katherine M. Howard, Karl Kingsley
Dentistry Journal.2024; 12(3): 56. CrossRef
Usefulness Analysis of Urine Samples for Early Screening of Human Papilloma Virus Infection
Yoon Sung Choi, Hyunwoo Jin, Kyung Eun Lee
Journal of Cancer Prevention.2019; 24(4): 240. CrossRef
Relationship between Expression of P16 and Ki-67 and Persistent Infection of HPV in Cervical Carcinoma Patients
群欢黄
Advances in Clinical Medicine.2018; 08(08): 776. CrossRef
Analysis of Sequence Variation and Risk Association of Human Papillomavirus 52 Variants Circulating in Korea
Youn Jin Choi, Eun Young Ki, Chuqing Zhang, Wendy C. S. Ho, Sung-Jong Lee, Min Jin Jeong, Paul K. S. Chan, Jong Sup Park, Xuefeng Liu
PLOS ONE.2016; 11(12): e0168178. CrossRef

Immunohistochemical Classification of Primary and Secondary Glioblastomas: Kyu Sang Lee, Gheeyoung Choe, Kyung Han Nam, An Na Seo, Sumi Yun, Kyung Ju Kim, Hwa Jin Cho, Sung Hye Park; Korean J Pathol. 2013;47(6):541-548. Published online December 24, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.6.541

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Abstract PDF

Background

Glioblastomas may develop de novo (primary glioblastomas, P-GBLs) or through progression from lower-grade astrocytomas (secondary glioblastomas, S-GBLs). The aim of this study was to compare the immunohistochemical classification of glioblastomas with clinically determined P-GBLs and S-GBLs to identify the best combination of antibodies for immunohistochemical classification.

Methods

We evaluated the immunohistochemical expression of epidermal growth factor receptor (EGFR), p53, and isocitrate dehydrogenase 1 (IDH-1) in 150 glioblastoma cases.

Results

According to clinical history, the glioblastomas analyzed in this study consisted of 146 P-GBLs and 4 S-GBLs. Immunohistochemical expression of EGFR, p53, and IDH-1 was observed in 62.6%, 49.3%, and 11.1%, respectively. Immunohistochemical profiles of EGFR(+)/p53(-), IDH-1(-)/EGFR(+)/p53(-), and EGFR(-)/p53(+) were noted in 41.3%, 40.2%, and 28.7%, respectively. Expression of IDH-1 and EGFR(-)/p53(+) was positively correlated with young age. The typical immunohistochemical features of S-GBLs comprised IDH-1(+)/EGFR(-)/p53(+), and were noted in 3.6% of clinically P-GBLs. The combination of IDH-1(-) or EGFR(+) was the best set of immunohistochemical stains for identifying P-GBLs, whereas the combination of IDH-1(+) and EGFR(-) was best for identifying S-GBLs.

Conclusions

We recommend a combination of IDH-1 and EGFR for immunohistochemical classification of glioblastomas. We expect our results to be useful for determining treatment strategies for glioblastoma patients.

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Baraa Dabboucy, Philippe Younes, Abdallah Rahbani, Elie Fahed, Gérard Abadjian
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Mukesh Barange, Sridhar Epari, Mamta Gurav, Omshree Shetty, Ayushi Sahay, Prakash Shetty, Jayantsastri Goda, Aliasagar Moyiadi, Tejpal Gupta, Rakesh Jalali
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Michael Nweke, Gabriel Ogun, Amos Adeleye, Clement A. Okolo, Adekunle Adesina
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Laura A. Lozano-Trujillo, Diana K. Garzón-Perdomo, Andrea C.R. Vargas, Lina M. de los Reyes, Marco F. Avila-Rodriguez, Olivia T.G. Gay, Liliana F. Turner
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Ádám Nagy, Ferenc Garzuly, Gergely Padányi, Iván Szűcs, Ádám Feldmann, Balázs Murnyák, Tibor Hortobágyi, Bernadette Kálmán
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Egyptian Journal of Pathology.2016; 36(2): 282. CrossRef

Human Papillomavirus Prevalence and Cell Cycle Related Protein Expression in Tonsillar Squamous Cell Carcinomas of Korean Patients with Clinicopathologic Analysis: Miji Lee, Sung Bae Kim, Sang-wook Lee, Jong-Lyel Roh, Seung-Ho Choi, Soon Yuhl Nam, Sang Yoon Kim, Kyung-Ja Cho; Korean J Pathol. 2013;47(2):148-157. Published online April 24, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.2.148

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Abstract PDF

Background

Human papillomavirus (HPV)-related tonsillar squamous cell carcinoma (TSCC) has recently been characterized as a distinct subset with a favorable prognosis. The prevalence and clinicopathologic significance of HPV-related TSCC in Koreans are not well known.

Methods

HPV in situ hybridization (ISH) accompanied by p53, p16, pRb, and cyclin D1 immunohistochemical staining were performed on 89 resection cases of TSCC from 2000 through 2010.

Results

HPV was detected by ISH in 59 of 89 cases (66.3%). HPV-positive TSCCs were more common in younger ages (p=0.005), and tumor sizes were smaller in the HPV-positive compared to the HPV-negative group (p=0.040). Positive HPV staining was significantly correlated with p16 expression (p<0.001), pRb inactivation (p=0.003), and cyclin D1 down-regulation (p<0.001) but not with p53 expression (p=0.334). Seventeen cases that showed p16-immunopositivity with HPV-negativity by ISH were retested by HPV typing; HPV DNA was not detected in all cases. There was no significant difference between HPV-positive and HPV-negative patients either in the disease-specific survival (DSS, p=0.857) or overall survival (p=0.910). Furthermore, pRb-inactivated cases showed better DSS (p=0.023), and p53-positive cases showed worse DSS (p=0.001).

Conclusions

Although high HPV prevalence was noted, it was not correlated with histopathologic findings or survival benefit. In addition to p53 expression, pRb inactivation along with p16 overexpression and down-regulation of cyclin D1 are thought to be important pathogenetic steps for developing TSCCs.

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Ha Young Park, Joong Seob Lee, Jee Hye Wee, Jeong Wook Kang, Eun Soo Kim, Taeryool Koo, Hee Sung Hwang, Hyo Jung Kim, Ho Suk Kang, Hyun Lim, Nan Young Kim, Eun Sook Nam, Seong Jin Cho, Mi Jung Kwon
Biomedicines.2023; 11(3): 851. CrossRef
Clinicopathologic characterization of cervical metastasis from an unknown primary tumor: a multicenter study in Korea
Miseon Lee, Uiree Jo, Joon Seon Song, Youn Soo Lee, Chang Gok Woo, Dong-Hoon Kim, Jung Yeon Kim, Sun Och Yoon, Kyung-Ja Cho
Journal of Pathology and Translational Medicine.2023; 57(3): 166. CrossRef
Negative Prognostic Implication of TERT Promoter Mutations in Human Papillomavirus–Negative Tonsillar Squamous Cell Carcinoma Under the New 8th AJCC Staging System
Hyunchul Kim, Mi Jung Kwon, Bumjung Park, Hyo Geun Choi, Eun Sook Nam, Seong Jin Cho, Kyueng-Whan Min, Eun Soo Kim, Hee Sung Hwang, Mineui Hong, Taeryool Koo, Hyo Jung Kim
Indian Journal of Surgical Oncology.2021; 12(S1): 134. CrossRef
Prevalence of high-risk human papillomavirus and its genotype distribution in head and neck squamous cell carcinomas
Yuil Kim, Young-Hoon Joo, Min-Sik Kim, Youn Soo Lee
Journal of Pathology and Translational Medicine.2020; 54(5): 411. CrossRef
Frequent hepatocyte growth factor overexpression and low frequency of c-Met gene amplification in human papillomavirus–negative tonsillar squamous cell carcinoma and their prognostic significances
Mi Jung Kwon, Dong Hoon Kim, Hye-Rim Park, Hyung Sik Shin, Ji Hyun Kwon, Dong Jin Lee, Jin Hwan Kim, Seong Jin Cho, Eun Sook Nam
Human Pathology.2014; 45(7): 1327. CrossRef

Expression of CHOP in Squamous Tumor of the Uterine Cervix: Hyun Hee Chu, Jun Sang Bae, Kyoung Min Kim, Ho Sung Park, Dong Hyu Cho, Kyu Yun Jang, Woo Sung Moon, Myoung Jae Kang, Dong Geun Lee, Myoung Ja Chung; Korean J Pathol. 2012;46(5):463-469. Published online October 25, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.5.463

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Abstract PDF

Background

High-risk human papillomavirus (HR-HPV) infection and abnormal p53 expression are closely involved in carcinogenesis of squamous cell carcinoma (SqCC) of uterine cervix. Recent studies have suggested that virus-induced endoplasmic reticulum (ER) stress modulates various cell survival and cell death signaling pathways. The C/EBP homologous protein (CHOP) is associated with ER stress-mediated apoptosis and is also involved in carcinogenesis of several human cancers. We hypothesized that CHOP is involved in the carcinogenesis of uterine cervical cancer in association with HR-HPV and/or p53.

Methods

Immunohistochemistry was used to analyze CHOP and p53 protein expression of tissue sections from 191 patients with invasive cancer or preinvasive lesions of the uterine cervix (61 cases of SqCC, 66 cases of cervical intraepithelial neoplasia [CIN] III, and 64 cases of CIN I).

Results

CHOP was expressed in 59.4% of CIN I, 48.5% of CIN III, and 70.5% of SqCC cases. It was also significantly more frequent in invasive SqCC than in preinvasive lesions (p=0.042). Moreover, CHOP expression significantly correlated with HR-HPV infection and p53 expression (p=0.009 and p=0.038, respectively).

Conclusions

Our results suggest that CHOP is involved in the carcinogenesis of the uterine cervix SqCC via association with HR-HPV and p53.

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Xiao-Juan Zhu, She-Gan Gao, San-Qiang Li, Zhen-Guo Shi, Zhi-Kun Ma, Shan-Shan Zhu, Xiao-Shan Feng
Clinics and Research in Hepatology and Gastroenterology.2015; 39(3): 391. CrossRef
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