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Advances in Comparative Oncology: Naturally Developing Tumors in Animals for Investigating Cancer Biology and Therapy

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A special issue of Animals (ISSN 2076-2615). This special issue belongs to the section "Veterinary Clinical Studies".

Deadline for manuscript submissions: 30 June 2025 | Viewed by 20861

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Special Issue Editors

Dr. Marcella Massimini

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Guest Editor

Faculty of Veterinary Medicine, University of Teramo, 64100 Teramo, Italy
Interests: comparative oncology; molecular pathways and biological markers involved in carcinogenesis

Prof. Dr. Mariarita Romanucci

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Faculty of Veterinary Medicine, University of Teramo, 64100 Teramo, Italy
Interests: veterinary and comparative oncology; heat shock/stress proteins in cancer

Prof. Dr. Leonardo Della Salda

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Department of Veterinary Medicine, University of Teramo, Teramo, Italy
Interests: tumors in domestic mammals; heat shock proteins; oncoproteins
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Carlos E. Alvarez

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Center for Clinical and Translational Research, The Abigail Wexner Research Instituteat Nationwide Children's Hospital; and Departments of Pediatrics and Veterinary Clinical Sciences, The Ohio State University Colleges of Medicine and Veterinary Medicine, Columbus, OH, USA
Interests: canine complex genetics; human-canine comparative genomics; animal models of disease; oncology; behavior; psychopathology; pleiotropy; molecular pharmacology

Special Issue Information

Dear Colleagues,

Comparative oncology is a rapidly expanding field of study focusing on naturally developing tumors in animals for increasing knowledge in cancer biology and therapy. Research studies from comparative oncology can integrate scientific findings to better understand the pathobiology of cancer, investigate cancer-associated genes and proteins, and translate these findings into novel therapies to benefit both animals and humans, in a One Health perspective.

Thus, the goal of this Special Issue is to synthesize our current knowledge of animal tumors with a comparative oncology approach, and to stimulate interdisciplinary collaborative research efforts aimed at advancing both animal and human health.

For this Special Issue, we invite scientists to submit original research articles on any aspect concerning comparative oncology, with particular interest on canine and feline tumors, as a group of naturally occurring malignancies similar in tumor biology and behavior to human cancers. Both biology-based and translational research studies, as well as review articles, are welcome.

Dr. Marcella Massimini
Prof. Dr. Mariarita Romanucci
Prof. Dr. Leonardo Della Salda
Prof. Dr. Carlos E. Alvarez
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. Animals 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 2400 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

animals
cancer therapy
comparative oncology
naturally developing cancers
translational research
tumor biology

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Published Papers (9 papers)

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Research

11 pages, 1407 KiB

Open AccessCommunication

Immunohistochemical Characterization of Feline Giant Cell Tumor of Bone (GCTb): What We Know and What We Can Learn from the Human Counterpart

by Ilaria Porcellato, Giuseppe Giglia and Leonardo Leonardi

Animals 2025, 15(5), 699; https://doi.org/10.3390/ani15050699 - 27 Feb 2025

Viewed by 577

Abstract

Giant cell tumor of bone (GCTb), formerly also known as osteoclastoma, is a pathological entity that in veterinary medicine is still undefined and, probably, underdiagnosed. In humans, GCTb is recognized as a primary benign bone tumor, locally aggressive, with high local recurrence rates, with controversial histogenesis that can rarely progress or present as a malignant form. In pets, this tumor is still considered rare, though the possibility of underdiagnosis is significant. Hence, the aim of the present study is to provide a histological and immunohistochemical characterization of a small case series of presumptive feline GCTb, comparing our results to the data reported for the human counterpart. Searching our archive, we found, from 2010 to 2023, only three diagnosed cases of GCTb from domestic cats (felis catus). After diagnosis revision, the samples were submitted to immunohistochemistry for Iba1, TRAP, SATB2, RUNX2, RANK, karyopherin α2 (KPNA-2), and osteocalcin. Ki-67 index was also evaluated. Results showed that the multinucleated giant cells were positive for Iba1, TRAP, and RANK, accounting for their osteoclastic origin. On the other side, mononuclear cells were mostly positive for osteoblast markers such as RUNX2, SATB2, and KPNA-2, whereas tumor-associated macrophages showed positivity for Iba1. Hence, results on the cell types characterizing the feline GCTb were comparable to those described in the human form of the tumor. Currently, diagnostic criteria for GCTBs in cats and, in domestic animals more broadly, are still lacking. This study provides valuable data into the immunohistochemical characteristics of the cell populations in feline GCTBs, enhancing veterinarians’ and pathologists’ knowledge for its diagnosis, ultimately improving patient care. Larger case series, complete with follow-up information, molecular analyses for specific mutations, and imaging of both tumors and patients, are needed to improve identification and achieve greater sensitivity in diagnosing this unique tumor. Full article

(This article belongs to the Special Issue Advances in Comparative Oncology: Naturally Developing Tumors in Animals for Investigating Cancer Biology and Therapy)

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16 pages, 1188 KiB

Open AccessFeature PaperArticle

Evaluation of Serum YKL-40 in Canine Multicentric Lymphoma: Clinical and Diagnostic Implications

by Chien-Chun Kuo, Jih-Jong Lee, Shang-Lin Wang, Yuan-Yuan Xia and Albert Taiching Liao

Animals 2024, 14(23), 3391; https://doi.org/10.3390/ani14233391 - 25 Nov 2024

Viewed by 896

Abstract

YKL-40, a secretory glycoprotein, is known as a prognostic biomarker in human cancers, but its role in canine multicentric lymphoma is not well understood. This study aimed to investigate serum YKL-40 levels in thirty dogs with multicentric lymphoma to determine their prognostic value, association with patient characteristics, and potential to predict chemotherapy response. Serum samples were collected before, during, and after chemotherapy, and YKL-40 level was measured using ELISA. The results showed that the pretreatment serum YKL-40 levels were significantly higher in dogs with multicentric lymphoma (394.0 pg/mL, n = 30) than in healthy controls (218.6 pg/mL, n = 11) (p = 0.012). While a cutoff value of 445.1 pg/mL was observed, further studies are needed to clarify its diagnostic utility. Dogs with clinical stage V had the highest YKL-40 levels (p = 0.027), potentially reflecting disease severity. Furthermore, YKL-40 levels decreased after chemotherapy (p = 0.030). However, YKL-40 levels showed no significant association with progression-free survival (PFS) (HR = 0.93, p = 0.830) or overall survival (OS) (HR = 0.99, p = 0.267). In conclusion, serum YKL-40 levels may potentially detect the disease severity, but its prognostic role remains uncertain. Further studies are required to evaluate serum YKL-40 levels as a potential indicator of treatment response or disease recurrence. Full article

(This article belongs to the Special Issue Advances in Comparative Oncology: Naturally Developing Tumors in Animals for Investigating Cancer Biology and Therapy)

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14 pages, 8467 KiB

Open AccessArticle

Comparison of MMP-2, MMP-9, COX-2, and PGP Expression in Feline Injection-Site and Feline Noninjection-Site Sarcomas—Pilot Study

by Agata Wojtkowska, Anna Małek, Sławomir Giziński, Rafał Sapierzyński, Anna Rodo, Justyna Sokołowska, Katarzyna A. Zabielska-Koczywąs, Anna Wojtalewicz, Magdalena Walewska, Ewa Kautz, Magdalena Ostrzeszewicz and Roman Lechowski

Animals 2024, 14(14), 2110; https://doi.org/10.3390/ani14142110 - 19 Jul 2024

Viewed by 1741

Abstract

Feline injection-site sarcomas (FISSs) are aggressive neoplasms that have been associated mostly with vaccination. Feline noninjection-site sarcomas (non-FISSs) are less frequently observed in cats and may arise in any anatomic site. This study aimed to determine the differences in the expression of the selected proteins (matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), cyclooxygenase-2 (COX-2), and P-glycoprotein (PGP)) and their correlation with the mitotic count in FISS and non-FISS, in order to characterize their immunohistochemical features. A preliminary study of eleven samples of FISS and eight samples of non-FISS was performed using immunohistochemistry. Among all the tested sarcomas, 80.4% of the tumors were positive for COX-2, 90.2% were positive for MMP-9, and 100% were positive for PGP. The results showed that the expressions of COX-2, MMP-9, and PGP were significantly higher in FISS than in non-FISS (COX-2—p ≤ 0.001; MMP-9—p ≤ 0.05; and PGP—p ≤ 0.05). A Spearman rank correlation analysis showed a moderate negative correlation between the expression of COX-2 and MMP-9 in FISS (r = −0.52). A strong negative correlation between COX-2 and PGP (r = −0.81), a moderate positive correlation between MMP-2 and MMP-9 (r = +0.69), and a moderate negative correlation between MMP-2 and PGP (r = −0.44) were observed in non-FISS. In summary, our study presents the immunohistochemical profile of the proteins involved with inflammation and carcinogenesis in FISS and non-FISS, which can contribute to expanding the knowledge of tumor biology. Full article

(This article belongs to the Special Issue Advances in Comparative Oncology: Naturally Developing Tumors in Animals for Investigating Cancer Biology and Therapy)

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20 pages, 58400 KiB

Open AccessArticle

Immunohistochemical Detection of Indoleamine 2,3-Dioxygenase in Spontaneous Mammary Carcinomas of 96 Pet Rabbits

by Sandra Schöniger, Sophie Degner, Claudia Schandelmaier, Heike Aupperle-Lellbach, Qian Zhang and Hans-Ulrich Schildhaus

Animals 2024, 14(14), 2060; https://doi.org/10.3390/ani14142060 - 13 Jul 2024

Viewed by 2005

Abstract

For mammary carcinomas in pet rabbits, prognostic biomarkers are poorly defined, and treatment is limited to surgical excision. Additional treatment options are needed for rabbit patients for which surgery is not a suitable option. In human breast cancer, the immunosuppressive enzyme indoleamine 2,3-dioxygenase 1 (IDO1) represents a prognostic biomarker and possible therapeutic target. This retrospective immunohistochemical study examined IDO1 in 96 pet rabbit mammary carcinomas with known mitotic count, hormone receptor status, and percentage of stromal tumor infiltrating lymphocytes (TILs). Tumors were obtained from 96 pet rabbits with an average of 5.5 years. All rabbits with reported sex (n = 88) were female or female-spayed. Of the carcinomas, 94% expressed IDO1, and 86% had sparse TILs consistent with cold tumors. Statistically significant correlations existed between a higher percentage of IDO1-positive tumor cells, lower mitotic counts, and increased estrogen receptor expression. The threshold for significance was IDO1 staining in >10% of tumor cells. These results lead to the assumption that IDO1 expression contributes to tumorigenesis and may represent a prognostic biomarker and possible therapeutic target also in pet rabbit mammary carcinomas. They also support the value of rabbits for breast cancer research. Full article

(This article belongs to the Special Issue Advances in Comparative Oncology: Naturally Developing Tumors in Animals for Investigating Cancer Biology and Therapy)

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13 pages, 889 KiB

Open AccessArticle

An Evaluation of Hemostatic Dysregulation in Canine Multicentric Lymphoma

by Maria Ludovica Messina, Fausto Quintavalla, Angelo Pasquale Giannuzzi, Tommaso Furlanello and Marco Caldin

Animals 2024, 14(3), 500; https://doi.org/10.3390/ani14030500 - 2 Feb 2024

Cited by 2 | Viewed by 3373

Abstract

Multiple hemostatic abnormalities are associated with paraneoplastic syndrome and some malignant tumors. Lymphoma is the most common hematopoietic neoplasm in dogs, sometimes associated with hemostatic changes. The objectives of this study were to evaluate the behavior of coagulation parameters in dogs with multicentric lymphoma compared with diseased dogs without lymphoma, to separately evaluate the effect of immunophenotype (B lymphoma versus T lymphoma) on the variables of interest as well as the effect of disease stage (stage II to IV versus stage V). Specifically, a cross-sectional study was performed with a matched comparison group considering 170 dogs with B or T lymphoma (group 1) and 170 dogs with no lymphoma or other neoplastic processes but other diseases (group 0). Eight coagulation parameters were evaluated: platelet count (Plt), activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin time (TT), fibrinogen, fibrin/products of fibrinogen degradation (FDPs), fibrin D-dimers, and antithrombin (AT). Dogs with lymphoma showed prolonged PT and TT, decreased fibrinogen, increased FDP, and decreased Plt compared with group 0. The effect of disease stage was evaluated separately for dogs with stage II to IV lymphoma and dogs with stage V lymphoma; patients with stage II–IV lymphoma showed no significant differences, while in dogs with stage V lymphoma, a prolongation of PT and TT, a decrease in fibrinogen, an increase in FDPs and a decrease in Plt were found compared with the group 0. Finally, the comparison between B lymphoma and T lymphoma showed no significant differences in coagulation parameters between the two groups. Logistic regression analysis demonstrated that low fibrinogen and platelet levels were the most significant predictors of lymphoma in a cohort of canine patients. These hemostatic abnormalities in lymphoma appeared to be associated with the stage of the disease rather than the lymphoma immunophenotype. These findings pave the way for the possible scenario of lymphoma-associated fibrinolysis and the so far undescribed pattern of hyperfibrinolysis associated with the most severe stage of lymphoma. Full article

(This article belongs to the Special Issue Advances in Comparative Oncology: Naturally Developing Tumors in Animals for Investigating Cancer Biology and Therapy)

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13 pages, 1435 KiB

Open AccessArticle

Is Osteopontin a Good Marker for Bone Metastasis in Canine Mammary Gland Tumor and Prostate Cancer?

by Caroline Grisoni Sanchez, Marxa Leão Figueiredo, Laíza de Sartori Camargo, Luiz Guilherme Dercore Benevenuto, Zara Alves Lacerda and Carlos Eduardo Fonseca-Alves

Animals 2023, 13(20), 3211; https://doi.org/10.3390/ani13203211 - 14 Oct 2023

Cited by 2 | Viewed by 1894

Abstract

Osteopontin (OPN) is a protein synthesized by a large number of cells, and its overexpression has been associated with the development and prognosis of cancer. OPN overexpression has been claimed to be a marker for the development of bone metastasis in human cancers, but no prior research has investigated the association between OPN expression and the metastasis of canine mammary gland tumors (MGTs) and prostate cancer (PC). Therefore, we investigated OPN expression in MGTs and PC samples from 50 canine patients with or without metastasis (bone vs. other sites). Higher OPN expression was detected in primary tumor samples from animals with bone metastasis than in those without bone involvement (p = 0.0321). In MGT samples, a significantly lower survival rate was observed in patients with higher OPN expression (p = 0.0171). In animals with PC, there was a strong trend toward lower survival in animals with positive OPN expression; however, this trend was not statistically significant (p = 0.0779). From these findings, it can be concluded that OPN may be a promising target for future MGTs and PC studies because of its role in enhancing cell invasion and metastasis. Full article

(This article belongs to the Special Issue Advances in Comparative Oncology: Naturally Developing Tumors in Animals for Investigating Cancer Biology and Therapy)

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16 pages, 3445 KiB

Open AccessArticle

Canine Somatic Mutations from Whole-Exome Sequencing of B-Cell Lymphomas in Six Canine Breeds—A Preliminary Study

by Sungryong Kim, Namphil Kim, Hyo-Min Kang, Hye-Jin Jang, Amos Chungwon Lee and Ki-Jeong Na

Animals 2023, 13(18), 2846; https://doi.org/10.3390/ani13182846 - 7 Sep 2023

Viewed by 2148

Abstract

Canine lymphoma (CL) is one of the most common malignant tumors in dogs. The cause of CL remains unclear. Genetic mutations that have been suggested as possible causes of CL are not fully understood. Whole-exome sequencing (WES) is a time- and cost-effective method for detecting genetic variants targeting only the protein-coding regions (exons) that are part of the entire genome region. A total of eight patients with B-cell lymphomas were recruited, and WES analysis was performed on whole blood and lymph node aspirate samples from each patient. A total of 17 somatic variants (GOLIM4, ITM2B, STN1, UNC79, PLEKHG4, BRF1, ENSCAFG00845007156, SEMA6B, DSC1, TNFAIP1, MYLK3, WAPL, ADORA2B, LOXHD1, GP6, AZIN1, and NCSTN) with moderate to high impact were identified by WES analysis. Through a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of 17 genes with somatic mutations, a total of 16 pathways were identified. Overall, the somatic mutations identified in this study suggest novel candidate mutations for CL, and further studies are needed to confirm the role of these mutations. Full article

(This article belongs to the Special Issue Advances in Comparative Oncology: Naturally Developing Tumors in Animals for Investigating Cancer Biology and Therapy)

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11 pages, 267 KiB

Open AccessArticle

Psychological Stress Is Associated with Increased Cancer Risk in Dogs

by Isain Zapata, Alexander W. Eyre and Carlos E. Alvarez

Animals 2023, 13(11), 1869; https://doi.org/10.3390/ani13111869 - 3 Jun 2023

Cited by 1 | Viewed by 4079

Abstract

Although there is evidence that psychological stress may be associated with increased cancer risk, the effect of stress on cancer risk is difficult to study, both in humans, due to socioeconomic factors, and in animal models, due to questionable biological relevance. Here, we test whether heritable canine temperament that increases psychological stress is associated with cancer risk. The study data are breed-specific averages of incidences of multiple cancer types and of temperament classes. The latter are derived from a latent class analysis of behavioral questionnaires completed by owners (C-BARQ). We thus classified the dogs according to whether they are calm vs. reactive within and across breeds. Using meta-analysis approaches, we modeled the risk of multiple cancer types in calm vs. reactive dogs. We adjusted for breed averages of body mass and lifespan, which are common confounders that impact cancer. Our study confirms that body size has a significant effect of on risk of multiple types of cancers in dogs and shows for the first time that temperament also has a moderate effect. These findings suggest dog models of heritable psychological stress are suitable for molecular epidemiological and translational studies on its effects on cancer risk. Full article

(This article belongs to the Special Issue Advances in Comparative Oncology: Naturally Developing Tumors in Animals for Investigating Cancer Biology and Therapy)

12 pages, 1020 KiB

Open AccessArticle

Validation of p53 Immunohistochemistry (PAb240 Clone) in Canine Tumors with Next-Generation Sequencing (NGS) Analysis

by Barbara Brunetti, Dario de Biase, Giulia Dellapina, Luisa Vera Muscatello, Francesco Ingravalle, Giorgia Tura and Barbara Bacci

Animals 2023, 13(5), 899; https://doi.org/10.3390/ani13050899 - 1 Mar 2023

Cited by 4 | Viewed by 2408

Abstract

In human medicine, p53 immunohistochemistry (IHC) is a common method that is used for the identification of tumors with TP53 mutations. In veterinary medicine, several studies have performed IHC for p53 in canine tumors, but it is not known how well it actually predicts the mutation. The aim of this study was to estimate the accuracy of the IHC method for p53 (clone PAb240) using a lab-developed NGS panel to analyze TP53 mutations in a subset of malignant tumors in dogs. A total of 176 tumors were analyzed with IHC and then 41 were subjected to NGS analysis; among them, 15 were IHC positive and 26 were negative, and 16 out of 41 (39%) were found to be inadequate for NGS analysis. Excluding the non-evaluable cases at NGS, of the remaining eight IHC-positive cases, six were mutants and two were wild-type. Among the 17 IHC-negative cases, 13 were wild type, and 4 were mutants. The sensitivity was 60%, specificity was 86.7%, and the accuracy was 76%. These results suggest that when using IHC for p53 with this specific antibody to predict mutation, up to 25% wrong predictions can be expected. Full article

(This article belongs to the Special Issue Advances in Comparative Oncology: Naturally Developing Tumors in Animals for Investigating Cancer Biology and Therapy)

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