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Diagnostics
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Immunomarkers and Molecular Markers in the Diagnosis of Malignant Tumors
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Immunomarkers and Molecular Markers in the Diagnosis of Malignant Tumors

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (31 October 2021) | Viewed by 21690

Special Issue Editors

Prof. Dr. Gaetano Magro

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Guest Editor
General Surgical Pathologist, Director of Anatomic Pathology Laboratory, Department of Medical and Surgical Sciences and Advanced Technologies, Policlinico Hospital, University of Catania, Via S. Sofia 87, 95123 Catania, Italy
Interests: histological diagnoses of human tumors; immunohistochemistry; immunomarkers of malignant tumors; oncofetal expression of immunomarkers; pathological diagnoses of breast, soft tissue, thyroid, pediatric solid tumors
Special Issues, Collections and Topics in MDPI journals
Dr. Paolo G. Vigneri

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Guest Editor
1. Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy
2. Center of Experimental Oncology and Hematology, A.O.U. Policlinico-Vittorio Emanuele, 95123 Catania, Italy
Interests: clinical and molecular oncology
Special Issues, Collections and Topics in MDPI journals
Dr. Rosalba Parenti

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Guest Editor
Department of Biomedical and Biotechnological Sciences (BIOMETC), Section of Physiology, University of Catania, Via S. Sofia 89, 95123 Catania, Italy
Interests: physiology; morphology; molecular pathology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

A combined approach based on radiology and pathological examination currently represents the diagnostic gold standard of human neoplastic diseases. Unlike radiological imaging methods that allow a macroscopic approach to malignancies, pathology represents the cellular “point of view” of the different neoplastic lesions. and it is crucial in establishing the correct diagnosis, providing prognostic information, as well as the basis for the most appropriate therapeutic strategies. In daily practice, the introduction of immunohistochemistry, combined with “evergreen” morphology, has represented a turning point in the diagnostic interpretation of human tumors, allowing to identify the cell line of a morphologically poorly/undifferentiated neoplasm and/or
to evaluate the differential expression of protein markers by the different tumor types. In relatively recent years, the introduction of new ancillary methods, including real-time polymerase chain reaction (rt-PCR), fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS), through which the molecular landscape of neoplasms can be studied, has improved diagnostic accuracy. Such methods have allowed the identification of new “entity-defining” genetic alterations, some of which have been included in the definition of many tumor entities. Soft tissue and central nervous system tumors represent emblematic examples of the application of molecular biology to human oncology.

Accordingly, the identification of new immunomarkers along with molecular markers still represents one of the main goals of cancer scientific research. Based on this background, this Special Issue is devoted to the study of markers with both diagnostic and prognostic/predictive value in the field of human oncology. Manuscripts in which this aim is primarily approached by immunohistochemistry are particularly encouraged, but, being also aware of the potentials and limits of immunohistochemistry, the use of molecular methods, such as rt-PCR, FISH and NGS, is also welcome. Original and review papers are particularly desired. A limited number of uncommon and/or teaching case reports will also be considered.

Prof. Dr. Rosalba Parenti
Prof. Dr. Paolo G. Vigneri
Prof. Dr. Gaetano Magro
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Diagnostics is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Malignant tumors
  • Markers
  • Immunomarkers
  • Molecular markers
  • Diagnosis
  • Cancer

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Published Papers (7 papers)

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16 pages, 2639 KiB  
Article
KCTD15 Is Overexpressed in her2+ Positive Breast Cancer Patients and Its Silencing Attenuates Proliferation in SKBR3 CELL LINE
by Luigi Coppola, Simona Baselice, Francesco Messina, Rosa Giannatiempo, Amalia Farina, Luigi Vitagliano, Giovanni Smaldone and Marco Salvatore
Diagnostics 2022, 12(3), 591; https://doi.org/10.3390/diagnostics12030591 - 25 Feb 2022
Cited by 7 | Viewed by 3115
Abstract
Studies carried out in the last decade have demonstrated that the members of the KCTD protein family play active roles in carcinogenesis. Very recently, it has been reported that KCTD15, a protein typically associated with other physio-pathological processes, is involved in medulloblastoma and [...] Read more.
Studies carried out in the last decade have demonstrated that the members of the KCTD protein family play active roles in carcinogenesis. Very recently, it has been reported that KCTD15, a protein typically associated with other physio-pathological processes, is involved in medulloblastoma and leukemia. Starting with some preliminary indications that emerged from the analysis of online databases that suggested a possible overexpression of KCTD15 in breast cancer, in this study, we evaluated the expression levels of the protein in breast cancer cell lines and in patients and the effects of its silencing in the HER2+ cell model. The analysis of the KCTD15 levels indicates a significant overexpression of the protein in Luminal A and Luminal B breast cancer patients as well as in the related cell lines. The greatest level of over-expression of the protein was found in HER2+ patients and in the related SKBR3 cell line model system. The effects of KCTD15 silencing in terms of cell proliferation, cell cycle, and sensitivity to doxorubicin were evaluated in the SKBR3 cell line. Notably, the KCTD15 silencing in SKBR3 cells by CRISPR/CAS9 technology significantly attenuates their proliferation and cell cycle progression. Finally, we demonstrated that KCT15 silencing also sensitized SKBR3 cells to the cytotoxic agent doxorubicin, suggesting a possible role of the protein in anti HER2+ therapeutic strategies. Our results highlight a new possible player in HER2 breast cancer carcinogenesis, paving the way for its use in breast cancer diagnosis and therapy. Full article
(This article belongs to the Special Issue Immunomarkers and Molecular Markers in the Diagnosis of Malignant Tumors)
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17 pages, 2282 KiB  
Article
A Novel System for Semiautomatic Sample Processing in Chronic Myeloid Leukaemia: Increasing Throughput without Impacting on Molecular Monitoring at Time of SARS-CoV-2 Pandemic
by Stefania Stella, Silvia Rita Vitale, Michele Massimino, Adriana Puma, Cristina Tomarchio, Maria Stella Pennisi, Elena Tirrò, Chiara Romano, Federica Martorana, Fabio Stagno, Francesco Di Raimondo and Livia Manzella
Diagnostics 2021, 11(8), 1502; https://doi.org/10.3390/diagnostics11081502 - 20 Aug 2021
Cited by 1 | Viewed by 2526
Abstract
Molecular testing of the BCR-ABL1 transcript via real-time quantitative-polymerase-chain-reaction is the most sensitive approach for monitoring the response to tyrosine-kinase-inhibitors therapy in chronic myeloid leukaemia (CML) patients. Each stage of the molecular procedure has been standardized and optimized, including the total white blood [...] Read more.
Molecular testing of the BCR-ABL1 transcript via real-time quantitative-polymerase-chain-reaction is the most sensitive approach for monitoring the response to tyrosine-kinase-inhibitors therapy in chronic myeloid leukaemia (CML) patients. Each stage of the molecular procedure has been standardized and optimized, including the total white blood cells (WBCs) and RNA isolation methods. Here, we compare the performance of our current manual protocol to a newly semiautomatic method based on the Biomek i-5 Automated Workstations integrated with the CytoFLEX Flow Cytometer, followed by the automatic QIAsymphony system to facilitate high-throughput processing samples and reduce the hands-on time and the risk associated with SARS-CoV-2. The recovery efficiency was investigated in blood samples from 100 adults with CML. We observe a 100% of concordance between the two methods, with similar total WBCs isolated (median 1.137 × 106 for manual method vs. 1.076 × 106 for semiautomatic system) and a comparable quality and quantity of RNA extracted (median 103 ng/μL with manual isolation kit vs. 99.95 ng/μL with the QIAsymphony system). Moreover, by stratifying patients according to their BCR-ABL1 transcript levels, we obtained similar BCR-ABL1/ABL1IS values and ABL1 copies, and matched samples were assigned to the same group of molecular response. We conclude that this newly semiautomatic workflow has a performance comparable to our more laborious standard manual, which can be replaced, particularly when specimens from patients with suspected or confirmed SARS-CoV-2 infection need to be processed. Full article
(This article belongs to the Special Issue Immunomarkers and Molecular Markers in the Diagnosis of Malignant Tumors)
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13 pages, 12843 KiB  
Article
The Wide Morphological Spectrum of Deep (Aggressive) Angiomyxoma of the Vulvo-Vaginal Region: A Clinicopathologic Study of 36 Cases, including Recurrent Tumors
by Gaetano Magro, Giuseppe Angelico, Michal Michal, Giuseppe Broggi, Gian Franco Zannoni, Renato Covello, Stefano Marletta, Lucia Salvatorelli and Rosalba Parenti
Diagnostics 2021, 11(8), 1360; https://doi.org/10.3390/diagnostics11081360 - 28 Jul 2021
Cited by 6 | Viewed by 2387
Abstract
Background: Deep angiomyxoma (DAM) is currently included in the category of “specific stromal tumors of the lower female genital tract”, along with angiomyofibroblastoma, cellular angiofibroma and myofibroblastoma. Given the high rate of local recurrences, it is crucial to recognize DAM from other tumors [...] Read more.
Background: Deep angiomyxoma (DAM) is currently included in the category of “specific stromal tumors of the lower female genital tract”, along with angiomyofibroblastoma, cellular angiofibroma and myofibroblastoma. Given the high rate of local recurrences, it is crucial to recognize DAM from other tumors that possess indolent behaviour. In the present paper, we analyzed the morphological and immunohistochemical features of 42 surgically-resected vulvo-vaginal DAMs (36 primary and 6 recurrent lesions) in order to widen the morphological spectrum of this uncommon tumor. Methods: A series of 36 cases of surgically-resected primary vulvo-vaginal DAMs were retrospectively collected. Locally recurrent tumors were also available for six of these cases. Results: Out of the primary tumors, 25 out of 36 exhibited the classic-type morphology of DAM. In the remaining cases (11/36 cases), the following uncommon features, which sometimes coexist with one another, were observed: (i) alternating myxoid and collagenized/fibrous areas; (ii) hypercellular areas; (iii) neurofibroma-like appearance; (iv) perivascular hyalinization; (v) microcystic/reticular stromal changes; (vi) “microvascular growth pattern”; (vii) perivascular cuffing; (viii) nodular leiomyomatous differentiation; (ix) hypocellular and fibro-sclerotic stroma. Among the six locally recurrent tumors the following features were observed: (i) classic-type morphology; (ii) hypocellular fibro-sclerotic stroma; (iii) extensive perivascular hyalinization, lumen obliteration and formation of confluent nodular sclerotic masses; (iv) hypercellularity. Immunohistochemically, the neoplastic cells of classic-type DAM in both primary and recurrent tumors were diffusely stained with desmin, suggesting a myofibroblastic nature; in contrast, the neoplastic cells showing elongated fibroblastic-like morphology and set in collagenized/fibrosclerotic stroma in both primary and recurrent tumors were negative or only focally stained with desmin, which is consistent with a fibroblastic profile. Conclusion: Although diagnosis of DAM is usually straightforward if typical morphology is encountered, diagnostic problems may arise when a pathologist is dealing with unusual morphological features, especially hypercellularity, extensive collagenous/fibrosclerotic stroma or neurofibroma-like appearance. Full article
(This article belongs to the Special Issue Immunomarkers and Molecular Markers in the Diagnosis of Malignant Tumors)
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10 pages, 1200 KiB  
Communication
Regulation of Platelet-Derived ADAM17: A Biomarker Approach for Breast Cancer?
by Yanjun Zhou, Jonas S. Heitmann, Korbinian N. Kropp, Martina Hinterleitner, André Koch, Andreas D. Hartkopf, Helmut R. Salih, Clemens Hinterleitner and Stefanie Maurer
Diagnostics 2021, 11(7), 1188; https://doi.org/10.3390/diagnostics11071188 - 30 Jun 2021
Cited by 4 | Viewed by 2202
Abstract
Tumor progression and metastasis are critically dependent on the tumor microenvironment. A disintegrin and metalloproteinase 17 (ADAM17) is associated with shedding of several substrates involved in tumor progression and known to be expressed by platelets of healthy donors and patients with solid tumors. [...] Read more.
Tumor progression and metastasis are critically dependent on the tumor microenvironment. A disintegrin and metalloproteinase 17 (ADAM17) is associated with shedding of several substrates involved in tumor progression and known to be expressed by platelets of healthy donors and patients with solid tumors. Here, we report that platelet-derived ADAM17 (pADAM17) is regulated upon platelet activation of breast cancer patients, but not of healthy individuals. The observed downregulation of pADAM17 on platelets of cancer patients correlated with clinical parameters related to tumor progression including tumor stage and the occurrence of metastasis. Our data identify an association between platelet activation, modulation of platelet-derived ADAM17, and metastasis. In conclusion, we demonstrate that further development of pADAM17 as a liquid biomarker is warranted for monitoring disease progression in breast cancer. Full article
(This article belongs to the Special Issue Immunomarkers and Molecular Markers in the Diagnosis of Malignant Tumors)
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11 pages, 5565 KiB  
Article
An Emerging Anti-p16 Antibody-BC42 Clone as an Alternative to the Current E6H4 for Use in the Female Genital Tract Pathological Diagnosis: Our Experience and a Review on p16ink4a Functional Significance, Role in Daily-Practice Diagnosis, Prognostic Potential, and Technical Pitfalls
by Giuseppe Angelico, Angela Santoro, Frediano Inzani, Patrizia Straccia, Saveria Spadola, Damiano Arciuolo, Michele Valente, Nicoletta D’Alessandris, Roberta Benvenuto, Antonio Travaglino, Antonio Raffone and Gian Franco Zannoni
Diagnostics 2021, 11(4), 713; https://doi.org/10.3390/diagnostics11040713 - 16 Apr 2021
Cited by 8 | Viewed by 3489
Abstract
Background: To date, useful diagnostic applications of p16 IHC have been documented in gynecological pathology both for HPV-related and non-HPV-related lesions. In the present article, we reported our experience with the novel anti-p16 INK4a antibody (clone BC42), whose expression was tested across all [...] Read more.
Background: To date, useful diagnostic applications of p16 IHC have been documented in gynecological pathology both for HPV-related and non-HPV-related lesions. In the present article, we reported our experience with the novel anti-p16 INK4a antibody (clone BC42), whose expression was tested across all different gynecologic neoplasms; we also compared it to the traditional E6H4 clone. Moreover, we discussed and explored all the diagnostic applications of p16 IHC in gynecologic pathology. Methods: Consultation cases covering a 5-year period (2016–2020) regarding gynecological neoplastic and non-neoplastic lesions in which immunohistochemistry for p16, clone E6H4 was originally performed, were retrospectively retrieved from the files of our institution. Immunohistochemical staining for p16ink4a (BC42) [Biocare Medical group-Paceco USA; Bioptica Milan] and p16ink4a (E6H4) [Ventana Medical Systems-Arizona USA; Roche] was performed by using the Ventana automated immunostainer (Ventana Medical Systems, Tucson, AZ, USA). The immunostaining pattern was defined as negative, focal/patchy, or diffuse. Results: A total of 196 cases, represented by 36 high-grade SIL/CIN3 of the uterine cervix, 30 cervical adenocarcinomas, 22 cervical squamous cell carcinoma, 70 endometrial carcinomas, 25 high grade serous ovarian carcinomas, 6 uterine adenomatoid tumors, and 10 uterine leiomyosarcomas were included in this study. Results showed concordant staining quality of both clones on all tested neoplastic tissues. Conclusions: The novel anti-p16 antibody (BC42 clone) appeared as an alternative to the current E6H4 for use in gynecological neoplasms, offering similar levels of positivity and equally reliable staining results. Full article
(This article belongs to the Special Issue Immunomarkers and Molecular Markers in the Diagnosis of Malignant Tumors)
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11 pages, 1626 KiB  
Article
Evaluation of Beta-Catenin Subcellular Localization and Water Channel Protein AQP1 Expression as Predictive Markers of Chemo-Resistance in Ovarian High-Grade Serous Carcinoma: Comparative Study between Preoperative Peritoneal Biopsies and Surgical Samples
by Giuseppe Angelico, Antonio Ieni, Rosario Caltabiano, Angela Santoro, Frediano Inzani, Saveria Spadola, Giovanni Tuccari, Antonio Macrì and Gian Franco Zannoni
Diagnostics 2021, 11(3), 452; https://doi.org/10.3390/diagnostics11030452 - 5 Mar 2021
Cited by 6 | Viewed by 1968
Abstract
Background. Mutations of the β-catenin gene (CTNNB1), leading to aberrant immunohistochemical expression of β-catenin, represent a key mechanism of WNT/β-catenin pathway alteration in ovarian cancer. Aquaporin 1 (AQP1), as component of transmembrane-water-channel family proteins, has been documented in different human tumors and, recently, [...] Read more.
Background. Mutations of the β-catenin gene (CTNNB1), leading to aberrant immunohistochemical expression of β-catenin, represent a key mechanism of WNT/β-catenin pathway alteration in ovarian cancer. Aquaporin 1 (AQP1), as component of transmembrane-water-channel family proteins, has been documented in different human tumors and, recently, also in ovarian carcinoma. Only few studies have investigated the pathogenetic and prognostic role of β-catenin and AQP1 in ovarian carcinoma. Methods. We evaluated the expression of β-catenin and AQP1 in the preoperative peritoneal biopsies of 32 patients with peritoneal carcinosis, in which a histological diagnosis of high grade serous ovarian carcinoma was made. Furthermore, we have investigated their potential association with chemotherapeutic response evaluated at the omental site, as well as with clinico-pathological parameters. Results. Sixteen cases showed an aberrant membranous and cytoplasmic β-catenin staining pattern. The remaining 16 cases showed a preserved β-catenin expression localized only in cell membranes; 20 cases showed positive membranous staining (AQP1+), while 12 cases were considered negative (AQP1–). In the AQP+ group, we detected a significant association of AQP1 expression with poor chemotherapy response in omental tissues complete response score (CRS) 1-2, while a CRS 3 was never observed in all positive cases. Conclusions. Our findings suggest that β-catenin and AQP1 are expressed in a sub-group of ovarian tumors and play important roles in carcinogenesis. Patients affected by high grade serous carcinoma could be categorized in two different predictive groups: as AQP+ and AQP–. AQP+ cases may represent a subset of poor responders who could be considered more eligible for cytoreductive surgery rather than for neoadjuvant chemotherapy. Full article
(This article belongs to the Special Issue Immunomarkers and Molecular Markers in the Diagnosis of Malignant Tumors)
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8 pages, 1450 KiB  
Case Report
Medullary Carcinoma of the Gastrointestinal Tract: Report on Two Cases with Immunohistochemical and Molecular Features
by Cristina Colarossi, Marzia Mare, Giorgio La Greca, Marco De Zuanni, Lorenzo Colarossi, Eleonora Aiello, Eliana Piombino and Lorenzo Memeo
Diagnostics 2021, 11(10), 1775; https://doi.org/10.3390/diagnostics11101775 - 27 Sep 2021
Cited by 3 | Viewed by 3781
Abstract
Medullary carcinoma of the colon is a rare histological variant characterized by a poorly differentiated morphology, an aberrant immunophenotype, and microsatellite instability. Despite the lack of glandular differentiation, medullary carcinoma is reported to have a good prognosis. It is typically located in the [...] Read more.
Medullary carcinoma of the colon is a rare histological variant characterized by a poorly differentiated morphology, an aberrant immunophenotype, and microsatellite instability. Despite the lack of glandular differentiation, medullary carcinoma is reported to have a good prognosis. It is typically located in the right colon and frequently affects older women. Due to its clinical, histological, biological, and genetic peculiarity, medullary carcinoma requires an accurate diagnosis and the awareness of this diagnostic possibility. We describe the morphological, immunohistochemical, and molecular findings of two interesting cases, the first one in the right colon of a patient and the second one in the terminal ileum of a patient with Crohn’s disease. Deeper knowledge of all the biological and clinical features will allow appropriate and specific treatment of this tumor in the future. Full article
(This article belongs to the Special Issue Immunomarkers and Molecular Markers in the Diagnosis of Malignant Tumors)
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