Journal of Pathology and Translational Medicine

Original Article

TRPS1 expression in non-melanocytic cutaneous neoplasms: an immunohistochemical analysis of 200 cases: Yi A. Liu, Phyu P. Aung, Yunyi Wang, Jing Ning, Priyadharsini Nagarajan, Jonathan L. Curry, Carlos A. Torres-Cabala, Doina Ivan, Victor G. Prieto, Qingqing Ding, Woo Cheal Cho; J Pathol Transl Med. 2024;58(2):72-80. Published online February 26, 2024; DOI: https://doi.org/10.4132/jptm.2024.01.23

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Background
Although trichorhinophalangeal syndrome type 1 (TRPS1) was initially thought to be highly sensitive and specific for carcinomas and mesenchymal tumors of mammary origin, more recent data suggest its expression is not limited to breast neoplasms but also can be seen in other cutaneous neoplasms, such as extramammary Paget disease and squamous cell carcinoma (SCC) in situ.
Methods
Two-hundred cases of non-melanocytic cutaneous neoplasm, including basal cell carcinomas (BCCs) (n = 41), SCCs (n = 35), Merkel cell carcinomas (MCCs) (n = 25), and adnexal neoplasms (n = 99), were tested for TRPS1 expression using a monoclonal anti- TRPS1 rabbit anti-human antibody.
Results
TRPS1 expression was present in almost all cases of SCC (94%), with a median H-score of 200, while it was either absent or only focally present in most BCCs (90%), with a median H-score of 5. The difference between BCCs and SCCs in H-score was significant (p < .001). All MCCs (100%) lacked TRPS1 expression. TRPS1 expression was frequently seen in most adnexal neoplasms, benign and malignant, in variable intensity and proportion but was consistently absent in apocrine carcinomas. All endocrine mucin-producing sweat gland carcinomas (EMPSGCs) (100%, 6/6) showed diffuse and strong TRPS1 immunoreactivity, with a median H-score of 300, which was significantly different (p < .001) than that of BCCs.
Conclusions
Our study shows that TRPS1 may be an effective discriminatory marker for BCCs and SCCs. It also has a role in distinguishing BCCs from EMPSGCs.

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TRPS1 Expression Is Frequently Seen in a Subset of Cutaneous Mesenchymal Neoplasms and Tumors of Uncertain Differentiation: A Potential Diagnostic Pitfall
Moon Joo Kim, Yi A. Liu, Yunyi Wang, Jing Ning, Woo Cheal Cho
Dermatopathology.2024; 11(3): 200. CrossRef

Case Study

Intrathyroidal metastasis of tonsillar squamous cell carcinoma masquerading as a primary thyroid tumor: Jai-Hyang Go; J Pathol Transl Med. 2023;57(4):242-245. Published online July 11, 2023; DOI: https://doi.org/10.4132/jptm.2023.06.16

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Abstract PDF

Intrathyroidal metastasis of tonsillar squamous cell carcinoma is rare. To date, only six cases have been reported in the literature. This case was unusual and presented with thyromegaly before the diagnosis of the primary tumor. A 55-year-old male patient was suspected to have a primary thyroid tumor with nodal metastasis. The thyroid gland was diffusely enlarged, with no discernible mass. Histologically, the thyroid parenchyma revealed extensive endolymphatic tumor emboli, which were positive for p40 and p16 in a background of chronic lymphocytic thyroiditis. Positron emission tomography–computed tomography revealed hypermetabolic activity in the right tonsillar region. Tonsillar biopsy revealed human papillomavirus–positive squamous cell carcinoma. The present case is the first reported case of intrathyroidal metastasis of tonsillar squamous cell carcinoma with an initial clinical presentation of thyroid enlargement before the primary tumor of tonsillar cancer was diagnosed.

Citations

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Metastatic oropharyngeal squamous cell carcinoma to the thyroid: A case report and review of literature
Hannah Walker, Jed Speers, Milena Fabry, Sameep Kadakia
American Journal of Otolaryngology.2024; 45(4): 104306. CrossRef

Original Articles

Evaluation of the characteristics of multiple human papillomavirus (HPV) infections identified using the BD Onclarity HPV assay and comparison with those of single HPV infection: Jinhee Kim, Moonsik Kim, Ji Young Park; J Pathol Transl Med. 2022;56(5):289-293. Published online September 13, 2022; DOI: https://doi.org/10.4132/jptm.2022.08.02

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Abstract PDF Supplementary Material

Background
Human papillomavirus (HPV) infection is a major cause of cervical cancer and associated precursor lesions. Multiple HPV genotype infections have been reported. However, their clinicopathological characteristics still remain elusive.
Methods
For this study, 814 consecutive patients who had undergone colposcopy and HPV genotyping test using BD Onclarity HPV assay were retrospectively selected. Clinicopathological parameters of multiple HPV infections were compared with those of single HPV infection.
Results
Multiple HPV infections were found in 110 out of 814 cases (13.5%). Multiple HPV infections were associated with a significantly higher incidence of high-grade intraepithelial lesions (HSILs) compared with single HPV infection. Other high-risk HPV genotypes, in addition to HPV 16, were found more frequently in the multiple HPV infections group; these included HPV 51, 52, 33/58, 56/59/66, and 35/39/68. No specific coinfection pattern was not identified. Additionally, the number of HPV genotypes in multiple HPV infections was not associated with the progression to HSIL or squamous cell carcinoma.
Conclusions
Multiple HPV infections have distinct clinicopathological characteristics (compared with single HPV infection). As their biological behavior is uncertain, close and frequent follow-up is warranted.

Citations

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Relative distribution of HPV genotypes in histological cervical samples and associated grade lesion in a women population over the last 16 years in Burgundy, France
Christelle Auvray, Serge Douvier, Odile Caritey, Jean-Baptiste Bour, Catherine Manoha
Frontiers in Medicine.2023;[Epub] CrossRef
Epidemiologic characteristics of high-risk HPV and the correlation between multiple infections and cervical lesions
Qinli Luo, Xianghua Zeng, Hanyi Luo, Ling Pan, Ying Huang, Haiyan Zhang, Na Han
BMC Infectious Diseases.2023;[Epub] CrossRef

Frequency of PIK3CA mutations in different subsites of head and neck squamous cell carcinoma in southern Thailand: Arunee Dechaphunkul, Phatcharaporn Thongwatchara, Paramee Thongsuksai, Tanadech Dechaphunkul, Sarayut Lucien Geater; J Pathol Transl Med. 2022;56(3):126-133. Published online February 28, 2022; DOI: https://doi.org/10.4132/jptm.2022.01.04

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Abstract PDF

Background
Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations have been reported in many cancers, including head and neck squamous cell carcinoma (HNSCC). The frequency of these mutations varies among tumor locations and might be relevant to treatment outcomes among HNSCC. In this study, we examined the frequency of PIK3CA mutations in the different subsites of HNSCC.
Methods
Ninety-six fresh biopsy specimens were investigated for mutations in PIK3CA exons 4, 9, and 20 using allele-specific real-time polymerase chain reaction. Patient characteristics and survival were analyzed and compared between specimens with or without PIK3CA mutations.
Results
The study included primary tumors originating from the oral cavity (n=63), hypopharynx (n=23), and oropharynx (n=10). We identified mutations in 10.4% of patients (10 of 96 specimens). The overall mutational frequency was 17.4% (4/23) and 9.5% (6/63) in the hypopharynx and oral cavity, respectively. No patients with oropharyngeal carcinoma had mutations. Among the 10 mutant specimens, five were missense mutations (exon 9 [E545K] in two samples and exon 20 [H1047R] in three samples) and five were silent mutations in exon 20 (T1025T). Mutations were not found in exon 4. Among 84 patients with available clinical data, we found no significant differences in clinical characteristics and survival based on the presence or absence of PIK3CA mutations.
Conclusions
The results indicate that PIK3CA mutations are involved in HNSCC carcinogenesis, and the hypopharynx should be considered a primary site of interest for future studies, particularly in Southeast Asian populations.

Citations

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An empirical review on the resistance mechanisms of epidermal growth factor receptor inhibitors and predictive molecular biomarkers in colorectal cancer
Sankha Bhattacharya
Critical Reviews in Oncology/Hematology.2023; 183: 103916. CrossRef

Primary squamous cell carcinoma of the salivary gland: immunohistochemical analysis and comparison with metastatic squamous cell carcinoma: Uiree Jo, Joon Seon Song, Seung-Ho Choi, Soon Yuhl Nam, Sang Yoon Kim, Kyung-Ja Cho; J Pathol Transl Med. 2020;54(6):489-496. Published online August 31, 2020; DOI: https://doi.org/10.4132/jptm.2020.07.19

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Background
Primary squamous cell carcinoma (SCC) of the salivary gland is a rare disease, and distinguishing primary SCC from metastatic SCC is difficult. This study investigated the histological and immunohistochemical differences between primary and metastatic salivary gland SCC to improve the accuracy of diagnosis and to explore the pathogenesis of this disease.
Methods
Data of 16 patients who underwent surgery for SCC of salivary glands between 2000 and 2018 at Asan Medical Center were retrieved. Eight patients had a history of SCC at other sites, and eight patients had only salivary gland SCC. Immunostaining for p16, p53, androgen receptor (AR), gross cystic disease fluid protein 15 (GCDFP-15), and c-erbB2, as well as mucicarmine staining, were compared between the two groups.
Results
Most tumors were located in the center of the salivary glands with extraparenchymal extension. The histology of primary SCC of the salivary gland was consistent with moderately differentiated SCC with extensive desmoplastic reaction and peritumoral inflammation. Involvement of the salivary gland ducts and transition into the ductal epithelium were observed in two cases. Metastatic SCC resembled the primary tumor histologically and was associated with central necrosis. Both groups exhibited negative mucin staining. Two, one, and one primary SCC case exhibited AR, GCDFP-15, and c-erbB2 positivity, respectively.
Conclusions
A subset of primary SCCs originated in salivary ducts or was related to salivary duct carcinoma. Distinguishing primary from metastatic SCC of the salivary gland is difficult using histologic features and immunoprofiles. A comprehensive review of the medical history is essential.

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Sawako Ono, Katsutoshi Hirose, Yuji Hirata, Marie Yamada, Satoko Nakamura, Hidetaka Yamamoto
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology.2024;[Epub] CrossRef
A case of primary squamous cell carcinoma of the parotid gland and review of the literature
Jingli Zhao, Xinrong Nan, Chuhuan Zhou, Nan Jiang, Liangliang Tian
Journal of Case Reports and Images in Oncology.2024; 10(1): 7. CrossRef
Metastatic cutaneous squamous cell carcinoma accounts for nearly all squamous cell carcinomas of the parotid gland
Patrick J. Bradley, Göran Stenman, Lester D. R. Thompson, Alena Skálová, Roderick H. W. Simpson, Pieter J. Slootweg, Alessandro Franchi, Nina Zidar, Alfons Nadal, Henrik Hellquist, Michelle D. Williams, Ilmo Leivo, Abbas Agaimy, Alfio Ferlito
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Common skin cancers and their association with other non-cutaneous primary malignancies: a review of the literature
Lindsay Holic
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Salivary duct carcinoma with squamous differentiation: histomorphological and immunophenotypical analysis of six cases
Melad N Dababneh, Christopher C Griffith, Kelly R Magliocca, Ivan J Stojanov
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Carla Saoud, Hansen Lam, Sandra I. Sanchez, Zahra Maleki
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Michał Żurek, Łukasz Fus, Kazimierz Niemczyk, Anna Rzepakowska
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Sangeun Lee, Yun Sung Lim, Kyuho Lee, Bo Hae Kim
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Naomi Hardy, Joshua Thompson, Ranee Mehra, Cinthia B. Drachenberg, Kyle Hatten, John C. Papadimitriou
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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; J Pathol Transl Med. 2020;54(5):411-418. Published online July 21, 2020; DOI: https://doi.org/10.4132/jptm.2020.06.22

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Abstract PDF

Background
High-risk (HR) human papillomavirus (HPV) is found in a subset of head and neck (HN) squamous cell carcinomas (SCCs). For oropharyngeal SCCs, HR HPV positivity is known to be associated with good prognosis, and a separate staging system for HPV-associated carcinomas using p16 immunohistochemistry (IHC) as a surrogate test has been adopted in the 8th American Joint Committee on Cancer staging system. We examined the HR HPV status and the genotype distribution in five HN subsites.
Methods
Formalin-fixed paraffin-embedded tissue sections were used for p16 IHC and DNA extraction. HPV DNA detection and genotyping were done employing either a DNA chip-based or real-time polymerase chain reaction–based method.
Results
During 2011–2019, a total of 466 SCCs were tested for HPV DNA with 34.1% positivity for HR HPV. Among HN subsites, the oropharynx showed the highest HR HPV prevalence (149/205, 75.1%), followed by the sinonasal tract (3/14, 21.4%), larynx (5/43, 11.6%), hypopharynx (1/38, 2.6%), and oral cavity (1/166, 0.6%). The most common HPV genotype was HPV16 (84.3%) followed by HPV35 (6.9%) and HPV33 (4.4%). Compared with HR HPV status, the sensitivity and specificity of p16 IHC were 98.6% and 94.3% for the oropharynx, and 99.2% and 93.8% for the tonsil, respectively.
Conclusions
Using a Korean dataset, we confirmed that HR HPV is most frequently detected in oropharyngeal SCCs. p16 positivity showed a good concordance with HR HPV DNA for oropharyngeal and especially tonsillar carcinomas. The use of p16 IHC may further be extended to predict HR HPV positivity in sinonasal tract SCCs.

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Characteristics of human papillomavirus infection among oropharyngeal cancer patients: A systematic review and meta-analysis
Meimei Cui, Jinling Cheng, Huijuan Cheng, Ming Zhao, Dan Zhou, Min Zhang, Jingjing Jia, Limei Luo
Archives of Oral Biology.2024; 157: 105830. CrossRef
Impact of histopathological parameters in prognosis of oral squamous cell carcinoma
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Oral Diseases.2024;[Epub] CrossRef
High-risk HPV Does not Appear to be an Important Risk Factor for Sinonasal Carcinomas in Turkish Population: A Tertiary Center Experience
Evsen Apaydin Arikan, Levent Aydemir, Murat Ulusan, Dilek Yilmazbayhan, Yasemin Ozluk
International Journal of Surgical Pathology.2023; 31(2): 124. CrossRef
Practical Application of Circulating Tumor-Related DNA of Human Papillomavirus in Liquid Biopsy to Evaluate the Molecular Response in Patients with Oropharyngeal Cancer
Agnieszka M. Mazurek, Tomasz W. Rutkowski
Cancers.2023; 15(4): 1047. CrossRef
The Prevalence of HPV in Oral Cavity Squamous Cell Carcinoma
Seyed Keybud Katirachi, Mathias Peter Grønlund, Kathrine Kronberg Jakobsen, Christian Grønhøj, Christian von Buchwald
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Positive Rate of Human Papillomavirus and Its Trend in Head and Neck Cancer in South Korea
Hyun Woong Jun, Yong Bae Ji, Chang Myeon Song, Jae Kyung Myung, Hae Jin Park, Kyung Tae
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Shu Wang, Xibing Zhuang, Caixia Gao, Tiankui Qiao
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Peripheral type squamous cell carcinoma of the lung: clinicopathologic characteristics in comparison to the central type: Yeoun Eun Sung, Uiju Cho, Kyo Young Lee; J Pathol Transl Med. 2020;54(4):290-299. Published online June 17, 2020; DOI: https://doi.org/10.4132/jptm.2020.05.04

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Abstract PDF

Background
Squamous cell carcinomas (SqCCs) of the lung are known to arise more often in a central area but reports of peripheral SqCCs have increased, with a pathogenesis that is obscured. In this study, the clinicopathologic characteristics of peripheral lung SqCCs were studied and compared with those of the central type.
Methods
This study included 63 peripheral lung SqCCs and 48 randomly selected central cases; hematoxylin and eosin-stained slides of surgically resected specimens were reviewed in conjunction with radiologic images and clinical history. Cytokeratin-7 immunohistochemical staining of key slides and epidermal growth factor receptor (EGFR)/KRAS mutations tested by DNA sequencing were also included.
Results
Stages of peripheral SqCCs were significantly lower than central SqCCs (p=.016). Cystic change of the mass (p=.007), presence of interstitial fibrosis (p=0.007), and anthracosis (p=.049) in the background lung were significantly associated with the peripheral type. Cytokeratin-7 positivity was also higher in peripheral SqCCs with cutoffs of both 10% and 50% (p=.011). Pathogenic mutations in EGFR and KRAS were observed in only one case out of the 72 evaluated. The Cox proportional hazard model indicated a significantly better disease-free survival (p=.009) and the tendency of better overall survival (p=.106) in the peripheral type.
Conclusions
In peripheral type, lower stage is a favorable factor for survival but more frequent interstitial fibrosis and older age are unfavorable factors. Multivariate Cox analysis revealed that peripheral type is associated with better disease-free survival. The pathogenesis of peripheral lung SqCCs needs further investigation, together with consideration of the background lung conditions.

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Human Papillomavirus Serologic Profiles of Selected Filipinos with Head and Neck Squamous Cell Carcinoma: Pia Marie Albano, Christianne Salvador, Jose Orosa, Sheryl Racelis, Modesty Leaño, Angelika Michel, John Donnie Ramos, Dana Holzinger, Michael Pawlita; J Pathol Transl Med. 2019;53(5):273-279. Published online May 30, 2019; DOI: https://doi.org/10.4132/jptm.2019.05.12

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Abstract PDF

Background
The low prevalence of human papillomavirus (HPV) DNA and mRNA in biopsy samples of Filipinos with head and neck squamous cell carcinoma (HNSCC) has been reported previously. Here, the HPV serologic profiles of HNSCC cases were analyzed and associated with life-style and sexual practices.
Methods
Serum samples were collected between May 2012 and September 2013 from HNSCC patients (n = 22) in the northwest region of the Philippines, and age- and sex-matched clinically healthy controls. Antibodies to capsid and early oncoproteins of HPV16, 18, 31, 33, 45, 52, 58, 6, and 11 were analyzed using multiplex serology.
Results
Most of the cases were males with tumors of the oral cavity or larynx. Two of the cases tested positive for at least one of the early oncoproteins (E6, E7, E1, and/or E2) of HPV16, and 11 did not display reactivity to any HPV early or late oncoproteins. Of the controls, four tested positive for at least one of the HPV16 early oncoproteins, and 10 were non-reactive to all HPV types. Titers to HPV16 E6 or E7 of the seropositive cases and controls were considerably lower than those typically observed in economically developed countries.
Conclusions
The low HPV titers seen here are consistent with the results of molecular analyses for this population. Hence, the seropositivity of some of the HNSCC cases is likely an indication of prior exposure to the virus and not the presence of HPV-driven tumors.

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Social determinants of sex disparities in cancer in Southeast Asia
Ma. Veronica Pia N. Arevalo, Ethan Angelo S. Maslog, Katherine Donatela Manlongat, Eric David B. Ornos, Imjai Chitapanarux, Michelle Ann B. Eala, Edward Christopher Dee
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Case Study

Squamous Cell Carcinoma of the Extrahepatic Common Hepatic Duct: Myunghee Kang, Na Rae Kim, Dong Hae Chung, Hyun Yee Cho, Yeon Ho Park; J Pathol Transl Med. 2019;53(2):112-118. Published online October 1, 2018; DOI: https://doi.org/10.4132/jptm.2018.09.03

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Abstract PDF

We report a rare case of hilar squamous cell carcinoma. A 62-year-old Korean woman complaining of nausea was referred to our hospital. Her biliary computed tomography revealed a 28 mm-sized protruding solid mass in the proximal common bile duct. The patient underwent left hemihepatectomy with S1 segmentectomy and segmental excision of the common bile duct. Microscopically, the tumor was a moderately differentiated squamous cell carcinoma of the extrahepatic bile duct, without any component of adenocarcinoma or metaplastic portion in the biliary epithelium. Immunohistochemically, the tumor was positive for cytokeratin (CK) 5/6, CK19, p40, and p63. Squamous cell carcinoma of the extrahepatic bile duct is rare. To date, only 24 cases of biliary squamous cell carcinomas have been reported. Here, we provide a clinicopathologic review of previously reported extrahepatic bile duct squamous cell carcinomas.

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Ritu Nahar, Ian Holmes, Jeffrey Baliff, Austin Chiang, Thomas Kowalski
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ABCD. Arquivos Brasileiros de Cirurgia Digestiva (São Paulo).2021;[Epub] CrossRef
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Original Articles

An Immunohistochemical and Polarizing Microscopic Study of the Tumor Microenvironment in Varying Grades of Oral Squamous Cell Carcinoma: Aeman Khalid, Safia Siddiqui, Bharadwaj Bordoloi, Nafis Faizi, Fahad Samadi, Noora Saeed; J Pathol Transl Med. 2018;52(5):314-322. Published online July 27, 2018; DOI: https://doi.org/10.4132/jptm.2018.07.17

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Abstract PDF

Background
Invasion of epithelial cells into the connective tissue brings about massive morphological and architectural changes in the underlying stroma. Myofibroblasts reorganize the stroma to facilitate the movement of tumor cells leading to metastasis. The aim of this study was to determine the number and pattern of distribution of myofibroblasts and the qualitative and quantitative change that they cause in the collagen present in the stroma in various grades of oral squamous cell carcinoma (OSCC).
Methods
The study was divided into two groups with group I (test group, 65 cases) consisting of 29 cases of well-differentiated squamous cell carcinoma, 25 moderately differentiated SCC, and 11 poorly differentiated SCC, and group II (control group) consisting of 11 cases of normal mucosa. Sections from each sample were stained with anti–α-smooth muscle actin (α-SMA) antibodies, hematoxylin and eosin, and Picrosirius red. Several additional sections from each grade of OSCC were stained with Masson’s trichrome to observe the changes in collagen. For the statistical analysis, Fisher’s exact test, Tukey’s post hoc honest significant difference test, ANOVA, and the chi-square test were used, and p < .05 was considered statistically significant.
Results
As the tumor stage progressed, an increase in the intensity α-SMA expression was seen, and the network pattern dominated in more dedifferentiated carcinomas. The collagen fibers became thin, loosely packed, and haphazardly aligned with progressing cancer. Additionally, the mean area fraction decreased, and the fibers attained a greenish yellow hue and a weak birefringence when observed using polarizing light microscopy.
Conclusions
Myofibroblasts bring about numerous changes in collagen. As cancer progresses, there isincrease in pathological collagen,which enhances the movement of cells within the stroma.

Citations

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Multifractal Alterations in Oral Sub-Epithelial Connective Tissue During Progression of Pre-Cancer and Cancer
Debaleena Nawn, Sawon Pratiher, Subhankar Chattoraj, Debjani Chakraborty, Mousumi Pal, Ranjan Rashmi Paul, Srimonti Dutta, Jyotirmoy Chatterjee
IEEE Journal of Biomedical and Health Informatics.2021; 25(1): 152. CrossRef

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.

Citations

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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
Neoadjuvant treatment combined with planned endoscopic surgery in locally advanced sphenoid sinus basaloid squamous cell carcinoma
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
Carcinogenesis.2021; 42(8): 1100. CrossRef
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
Modern Pathology.2020; 33(7): 1242. CrossRef
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
Association study of cell cycle proteins and human papillomavirus in laryngeal cancer in Chinese population
Lifang Cui, Congling Qu, Honggang Liu
Clinical Otolaryngology.2019; 44(3): 323. CrossRef
Liver metastatic basaloid squamous cell carcinoma with negative expression of pancytokeratin: a case report and literature review
Linxiu Liu, Xuemin Xue, Liyan Xue
Diagnostic Pathology.2019;[Epub] CrossRef
Basaloid Squamous Cell Carcinoma at the Floor of the Mouth and Mandible: A Case Report
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
Oral Cancer.2018; 2(1-2): 7. CrossRef
Expression and role of EGFR, cyclin�D1 and KRAS in laryngocarcinoma tissues
Xinsheng Lin, Guofeng Wen, Shuangle Wang, Hangui Lu, Chuangwei Li, Xin Wang
Experimental and Therapeutic Medicine.2018;[Epub] CrossRef

Significance of Parafibromin Expression in Laryngeal Squamous Cell Carcinomas: Inju Cho, Mija Lee, Sharon Lim, Ran Hong; J Pathol Transl Med. 2016;50(4):264-269. Published online June 23, 2016; DOI: https://doi.org/10.4132/jptm.2016.04.24

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Abstract PDF

Background
Parafibromin is a product of the tumor suppressor gene that has been studied as a potential indicator of tumor aggressiveness in the parathyroid, breast, colorectum, and stomach. However, the clinical significance and potential function of parafibromin expression in head and neck squamous cell carcinomas remain largely unknown. The aim of this study was to evaluate the expression of parafibromin in laryngeal squamous cell carcinoma (LSCC) and to verify its potential as a biomarker of tumor behavior.
Methods
Parafibromin expression was evaluated in 30 cases of LSCC using immunohistochemistry. The correlations between parafibromin expression and clinicopathologic parameters were investigated.
Results
Parafibromin expression was positive in 15 cases (50%) and negative in 15 cases (50%). Tumor size and T stage showed a statistically significant inverse relationship with parafibromin expression (p=.028 and p<.001, respectively). Parafibromin expression was not associated with age, sex, lymph node metastasis, tumor differentiation, or tumor location. There was no statistically significant relationship between parafibromin expression and progression-free survival in the patients (p>.05).
Conclusions
Our results indicate that the downregulation or loss of parafibromin expression can be employed as a novel marker of tumor progression or aggressiveness in LSCC.

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Advances in the application of label‐free quantitative proteomics techniques in malignancy research
Xiao Meng, Dong Liu, Yan Guan
Biomedical Chromatography.2023;[Epub] CrossRef
The roles of the tumor suppressor parafibromin in cancer
Hua-chuan Zheng, Hang Xue, Cong-yu Zhang
Frontiers in Cell and Developmental Biology.2022;[Epub] CrossRef
The clinicopathological and prognostic significances of CDC73 expression in cancers: a bioinformatics analysis
Hua-Chuan Zheng, Bao-Cheng Gong, Shuang Zhao
Oncotarget.2017; 8(56): 95270. CrossRef

Prognostic Significance of Aquaporin 5 Expression in Non-small Cell Lung Cancer: Young Min Jo, Tae In Park, Hwa Young Lee, Ji Yun Jeong, Won Kee Lee; J Pathol Transl Med. 2016;50(2):122-128. Published online February 8, 2016; DOI: https://doi.org/10.4132/jptm.2015.10.31

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Abstract PDF

Background
Aquaporins are water channel proteins that play a major role in the movement of water in various human tissues. Recently, it has been found that aquaporins have influence in the carcinogenesis of human malignancies. We analyzed the prognostic impact of aquaporin 5 (AQP5) in non-small lung cancer (NSCLC). Methods: Seventy-six cases of NSCLC were studied, including 44 cases of adenocarcinoma (ADC) and 32 cases of squamous cell carcinoma (SQCC). Tissue microarray was constructed and immunohistochemical staining for AQP5 was performed. Results: AQP5 was positive in 59.2% of the total enrolled NSCLCs (63.7% in ADC and 53.1% in SQCC). The difference in expression of AQP5 according to the histologic grade of the tumor was significant (p<.047), but not in a serial order. When ADC and SQCC were separately evaluated, no significant difference was observed according to the histologic grade of the tumor (p=.076 in ADC and p=.631 in SQCC). No difference was observed between AQP5 expression and other demographic data and tumor characteristics. Disease-free survival (DFS) was higher in AQP5 negative cases than positive cases in ADC (p=.047), but no significance was found in SQCC (p=.068). We were unable to find a significance between AQP5 overexpression and overall survival in either ADC (p=.210) or SQCC (p=.533). Conclusions: AQP5 expression is associated with DFS in ADC of the lung and tumor grade of NSCLC. The present study suggests that AQP5 can be a prognostic factor of NSCLC.

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AQP5 promotes epithelial-mesenchymal transition and tumor growth through activating the Wnt/β-catenin pathway in triple-negative breast cancer
Zhengcai Zhu, Tao Li, Honggang Wang, Lianghe Jiao
Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis.2024; 829: 111868. CrossRef
Aquaporin-mediated dysregulation of cell migration in disease states
Ian M. Smith, Shohini Banerjee, Allison K. Moses, Kimberly M. Stroka
Cellular and Molecular Life Sciences.2023;[Epub] CrossRef
The Role of Aquaporin 5 (AQP5) in Lung Adenocarcinoma: A Review Article
Lukasz Jaskiewicz, Anna Romaszko-Wojtowicz, Anna Doboszynska, Agnieszka Skowronska
Cells.2023; 12(3): 468. CrossRef
Aquaporins 1, 3 and 5 in Different Tumors, their Expression, Prognosis Value and Role as New Therapeutic Targets
Mahdieh-Sadat Moosavi, Yalda Elham
Pathology & Oncology Research.2020; 26(2): 615. CrossRef
Aquaporins in lung health and disease: Emerging roles, regulation, and clinical implications
Ekta Yadav, Niket Yadav, Ariel Hus, Jagjit S. Yadav
Respiratory Medicine.2020; 174: 106193. CrossRef
Combined Systematic Review and Transcriptomic Analyses of Mammalian Aquaporin Classes 1 to 10 as Biomarkers and Prognostic Indicators in Diverse Cancers
Pak Hin Chow, Joanne Bowen, Andrea J Yool
Cancers.2020; 12(7): 1911. CrossRef
Prognostic Role of S100A8 and S100A9 Protein Expressions in Non-small Cell Carcinoma of the Lung
Hyun Min Koh, Hyo Jung An, Gyung Hyuck Ko, Jeong Hee Lee, Jong Sil Lee, Dong Chul Kim, Jung Wook Yang, Min Hye Kim, Sung Hwan Kim, Kyung Nyeo Jeon, Gyeong-Won Lee, Se Min Jang, Dae Hyun Song
Journal of Pathology and Translational Medicine.2019; 53(1): 13. CrossRef
Effect of FGF/FGFR pathway blocking on lung adenocarcinoma and its cancer‐associated fibroblasts
Ahmed E Hegab, Mari Ozaki, Naofumi Kameyama, Jingtao Gao, Shizuko Kagawa, Hiroyuki Yasuda, Kenzo Soejima, Yongjun Yin, Robert D Guzy, Yoshikazu Nakamura, David M Ornitz, Tomoko Betsuyaku
The Journal of Pathology.2019; 249(2): 193. CrossRef
Anti-cancer effect of Aquaporin 5 silencing in colorectal cancer cells in association with inhibition of Wnt/β-catenin pathway
Wei Wang, Qing Li, Tao Yang, Dongsheng Li, Feng Ding, Hongzhi Sun, Guang Bai
Cytotechnology.2018; 70(2): 615. CrossRef
Knockdown of aquaporin-5 sensitizes colorectal cancer cells to 5-fluorouracil via inhibition of the Wnt–β-catenin signaling pathway
Qing Li, Tao Yang, Dongsheng Li, Feng Ding, Guang Bai, Wei Wang, Hongzhi Sun
Biochemistry and Cell Biology.2018; 96(5): 572. CrossRef
Implications of KRAS mutations in acquired resistance to treatment in NSCLC
Marzia Del Re, Eleonora Rofi, Giuliana Restante, Stefania Crucitta, Elena Arrigoni, Stefano Fogli, Massimo Di Maio, Iacopo Petrini, Romano Danesi
Oncotarget.2018; 9(5): 6630. CrossRef

The Clinicopathological Significance of Epithelial Mesenchymal Transition Associated Protein Expression in Head and Neck Squamous Cell Carcinoma: Kyu Ho Kim, Lucia Kim, Suk Jin Choi, Jee Young Han, Joon Mee Kim, Young Chae Chu, Young-Mo Kim, In Suh Park, Joo Han Lim; Korean J Pathol. 2014;48(4):263-269. Published online August 26, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.4.263

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Abstract PDF

Background

Epithelial mesenchymal transition (EMT) has an important role in invasion and metastasis of tumor cells. The purpose of this study was to evaluate the roles of EMT-associated proteins on progression and metastasis as a prognostic/predictive factor in curatively-resected (R0) head and neck squamous cell carcinoma (HNSCC).

Methods

A total of 118 patients who received curative surgery for HNSCC at Inha University Hospital between January 1996 and December 2011 were included. We used protein immunohistochemistry to evaluate the expression of E-cadherin, vimentin, and EZH2 on tissue microarrays. Also, we reviewed all medical records and analyzed the relationship between the expression of EMT-associated proteins and prognosis.

Results

The E-cadherin-negative group showed more moderate/poor differentiation of cancer cell type than the higher E-cadherin-expressing group (p=.016) and high EZH2 expression was significantly correlated with nodal metastasis (p=.012). Our results demonstrate a significant association between high expression of EZH2 and vimentin and presence of distant progression (p=.026). However, expression of E-cadherin, vimentin, and EZH2 was not significantly associated with overall survival.

Conclusions

These findings suggest that an EMT-associated protein expression profile is correlated with aggressiveness of disease and prognosis, and could be a useful marker for determination of additional treatment in curatively-resected HNSCC patients.

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Polycomb repressive complex 2 and its core component EZH2: potential targeted therapeutic strategies for head and neck squamous cell carcinoma
Yuxi Cheng, Zhengzheng Song, Xiaodan Fang, Zhangui Tang
Clinical Epigenetics.2024;[Epub] CrossRef
Prognostic Value of TWIST1 and EZH2 Expression in Colon Cancer
Samar M. Abdel Raouf, Taiseer R. Ibrahim, Lobna A. Abdelaziz, Mohamed I. Farid, Salem Y Mohamed
Journal of Gastrointestinal Cancer.2021; 52(1): 90. CrossRef
HOXB5 acts as an oncogenic driver in head and neck squamous cell carcinoma via EGFR/Akt/Wnt/β-catenin signaling axis
Kyungmin Lee, Jae Won Chang, Chan Oh, Lihua Liu, Seung-Nam Jung, Ho-Ryun Won, Young Il Kim, Ki-Sang Rha, Bon Seok Koo
European Journal of Surgical Oncology.2020; 46(6): 1066. CrossRef
EZH2 overexpression in head and neck cancer is related to lymph node metastasis
Julie C. Nienstedt, Cornelia Schroeder, Till Clauditz, Ronald Simon, Guido Sauter, Adrian Muenscher, Marco Blessmann, Henning Hanken, Christina Pflug
Journal of Oral Pathology & Medicine.2018; 47(3): 240. CrossRef
MiR-876-5p modulates head and neck squamous cell carcinoma metastasis and invasion by targeting vimentin
Yibo Dong, Yang Zheng, Chundi Wang, Xu Ding, Yifei Du, Laikui Liu, Wei Zhang, Wei Zhang, Yi Zhong, Yunong Wu, Xiaomeng Song
Cancer Cell International.2018;[Epub] CrossRef
HMGA2 is associated with the aggressiveness of tongue squamous cell carcinoma
H Zhang, Z Tang, C Deng, Y He, F Wu, O Liu, C Hu
Oral Diseases.2017; 23(2): 255. CrossRef
miR-375 Regulates Invasion-Related Proteins Vimentin and L-Plastin
Lizandra Jimenez, Jihyeon Lim, Berta Burd, Thomas M. Harris, Thomas J. Ow, Nicole Kawachi, Thomas J. Belbin, Ruth Angeletti, Michael B. Prystowsky, Geoffrey Childs, Jeffrey E. Segall
The American Journal of Pathology.2017; 187(7): 1523. CrossRef
Functional and therapeutic significance of EZH2 in urological cancers
Xiaobing Liu, Qingjian Wu, Longkun Li
Oncotarget.2017; 8(23): 38044. CrossRef
EZH2, an on–off valve in signal network of tumor cells
Shanshan Sun, Feng Yu, Lun Zhang, Xuan Zhou
Cellular Signalling.2016; 28(5): 481. CrossRef
High EZH2 Protein Expression Is Associated with Poor Overall Survival in Patients with Luminal A Breast Cancer
Si-Hyong Jang, Jong Eun Lee, Mee-Hye Oh, Ji-Hye Lee, Hyun Deuk Cho, Kyung-Ju Kim, Sung Yong Kim, Sun Wook Han, Han Jo Kim, Sang Byung Bae, Hyun Ju Lee
Journal of Breast Cancer.2016; 19(1): 53. CrossRef
EZH2 promotes invasion and metastasis of laryngeal squamous cells carcinoma via epithelial-mesenchymal transition through H3K27me3
HuaNan Luo, Yuan Jiang, SiJing Ma, HuanHuan Chang, ChunXi Yi, Hui Cao, Ying Gao, HaiLi Guo, Jin Hou, Jing Yan, Ying Sheng, XiaoYong Ren
Biochemical and Biophysical Research Communications.2016; 479(2): 253. CrossRef

Primary Squamous Cell Carcinoma of the Upper Genital Tract: Utility of p16^INK4a Expression and HPV DNA Status in its Differential Diagnosis from Extended Cervical Squamous Cell Carcinoma: Su Hyun Yoo, Eun-Mi Son, Chang Okh Sung, Kyu-Rae Kim; Korean J Pathol. 2013;47(6):549-556. Published online December 24, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.6.549

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Abstract PDF

Background

Primary squamous cell carcinoma (SCC) of the upper genital tract, including the endometrium, fallopian tubes, and ovaries, is extremely rare. It must be distinguished from the mucosal extension of primary cervical SCC because determination of the primary tumor site is important for tumor staging. However, patients with SCC of the fallopian tubes or ovarian surface have often undergone prior hysterectomy with inadequate examination of the cervix, making it difficult to determine the primary site.

Methods

We compared histologic findings, p16^INK4a expression, and human papillomavirus (HPV) DNA status in four patients with primary SCC of the upper genital tract and five patients with primary cervical SCC extending to the mucosa of the upper genital tract.

Results

All five SCCs of cervical origin showed strong expression of p16^INK4a, whereas all four SCCs of the upper genital tract were negative, although one showed weak focal staining. Three of the five cervical SCCs were positive for HPV16 DNA, whereas all four primary SCCs of the upper genital tract were negative for HPV DNA.

Conclusions

Although a thorough histological examination is important, immunonegativity for p16^INK4a and negative for HPV DNA may be useful adjuncts in determining primary SCCs of the upper genital tract.

Citations

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Daniela Fanni, Michele Peiretti, Valerio Mais, Elena Massa, Clara Gerosa, Francesca Ledda, Maria Luisa Fais, Gavino Faa, Stefano Angioni
International Journal of Gynecological Pathology.2022; 41(4): 431. CrossRef
Molecular Analysis of HPV-independent Primary Endometrial Squamous Cell Carcinoma Reveals TP53 and CDKN2A Comutations
Mark R. Hopkins, Doreen N. Palsgrove, Brigitte M. Ronnett, Russell Vang, Jeffrey Lin, Tricia A. Murdock
American Journal of Surgical Pathology.2022; 46(12): 1611. CrossRef
Primary squamous cell carcinoma of the endometrium—Case report with cytological characteristics in direct and indirect endometrial samples
Sanda Rajhvajn, Ana Barišić, Lada Škopljanac‐Mačina, Danijela Jurič, Vesna Mahovlić
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Überraschung in der Abradatdiagnostik
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Der Pathologe.2015; 36(3): 317. CrossRef
Retropharyngeal Lymph Node Metastasis in 54 Patients with Oropharyngeal Squamous Cell Carcinoma Who Underwent Surgery-Based Treatment
Eun-Jae Chung, Go-Woon Kim, Bum-Ki Cho, Sung-Jin Cho, Dae-Young Yoon, Young-Soo Rho
Annals of Surgical Oncology.2015; 22(9): 3049. CrossRef

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