Immunohistochemical Evaluation of Canine Ovarian Tumors

Akihara, Y.; Shimoyama, Yumiko; Kawasako, Kazufumi; Komine, Misa; Hirayama, K.; Kagawa, Yumiko; Omachi, Tetsuo; Matsuda, Kazuo; Okamoto, Minoru; Kadosawa, Tsuyoshi; Taniyama, Hiroyuki

doi:10.1292/jvms.69.703

Cited by 22 publications

(11 citation statements)

References 15 publications

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“…The alpha‐inhibin immunohistochemical detection is a powerful tool to reach a definitive diagnosis in canine ovarian tumours, as it is not always easy to distinguish epithelial, stromal and germ granulosa cell tumours (GCTs) (Fig. ) (Marino et al., ; Akihara et al., ; Riccardi et al., ; Gómez‐Laguna et al., ). Inhibins secreted by canine GCTs, playing as tumour suppressor, could explain the frequently observed benign behaviour of these tumours.…”

Section: Tissue Distribution In Health and In Some Pathologic Conditionsmentioning

confidence: 99%

Activins and Inhibins: Expression and Role in Normal and Pathological Canine Reproductive Organs: A review

Marino¹,

Zanghì²

2012

Anat Histol Embryol

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Activins and inhibins are regulatory proteins of the reproductive function. Inhibins antagonise the activin signalling at different levels and are responsible for the negative feedback in the regulation of the release of pituitary follicle stimulating hormone (FSH), which, in turn, is promoted by locally produced activins. In the canine ovary, both peptides are expressed by developing follicles and corpora lutea. Activins may play a stimulatory role in follicular development, promoting the aromatase function; inhibins modulate these processes and suppress the hyperplasic/neoplastic stimuli. Activins are required for ovulation and corpus luteum formation, while inhibins stimulate progesterone synthesis. The exclusive production of alpha-inhibin by granulosa cells allows the peptide to be used as marker to identify canine ovarian stromal tumours by immunohistochemistry. In the male, activins are powerful morphogenetic factors in the foetal testis. In the adult, they display a modulating action on spermatogenesis and Sertoli cell function. Inhibins, produced mainly by Leydig cells, promote testosterone secretion. Canine testicular tumours, such as Leydig, Sertoli and granulosa cell tumours (GCTs), may express inhibin subunits and produce high circulating levels of these glycoproteins. In the canine prostate, activins inhibit epithelium proliferation, antagonising androgen effects, but they are synthesised under androgenic stimulus.

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Section: Tissue Distribution In Health and In Some Pathologic Conditionsmentioning

confidence: 99%

Activins and Inhibins: Expression and Role in Normal and Pathological Canine Reproductive Organs: A review

Marino¹,

Zanghì²

2012

Anat Histol Embryol

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“…Like its human counterpart, canine p53 is also found to be mutated in several types of dogs tumors (including osteosarcoma and mammary tumors) 25 . The dog also spontaneously develops ovarian cancer 26 and the incidence of ovarian tumors in dogs varies from 6 to 11%, epithelial tumors being dominant (50-60%) [26][27][28][29] . This frequency is still likely underestimated, because (1) most dog ovarian epithelial tumors fail to express detectable symptoms 27,30 and (2) family dogs are commonly ovariohysterectomized (spayed) early in life in the United States.…”

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confidence: 99%

A dog oviduct-on-a-chip model of serous tubal intraepithelial carcinoma

Ferraz

Nagashima

Venzac

et al. 2020

Sci Rep

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Ovarian cancer is the fifth cause of cancer-related mortality in women, with an expected 5-year survival rate of only 47%. High-grade serous carcinoma (HGSC), an epithelial cancer phenotype, is the most common malignant ovarian cancer. It is known that the precursors of HGSC originate from secretory epithelial cells within the Fallopian tube, which first develops as serous tubal intraepithelial carcinoma (STIC). Here, we used gene editing by CRISPR-Cas9 to knock out the oncogene p53 in dog oviductal epithelia cultured in a dynamic microfluidic chip to create an in vitro model that recapitulated human STIC. Similar to human STIC, the gene-edited oviduct-on-a-chip, exhibited loss of cell polarization and had reduced ciliation, increased cell atypia and proliferation, with multilayered epithelium, increased Ki67, PAX8 and Myc and decreased PTEN and RB1 mRNA expression. This study provides a biomimetic in vitro model to study STIC progression and to identify potential biomarkers for early detection of HGSC.Ovarian high-grade serous carcinoma (HGSC) and tubal epithelium share similar morphology, immuno-phenotype, and gene and protein expression patterns 1-3 . Transformed human Fallopian tube stem cells give rise to tumors that recapitulate the morphology and gene expression of HGSC after injection into immune-deficient mice 4 . Furthermore, most Fallopian tube cancer lesions (96%), such as serous tubal intraepithelial carcinoma (STIC), are marked by mutant p53, as are their metastatic form HGSC 5,6 . Past research on HGSC has used human tumor cells, but it has been hampered by the inefficiency of platting and sub-culturing of Fallopian tube epithelium, a process that involves a long period of fibroblast contamination reduction 7 . Furthermore, these processes result in the selection of specific cell populations, which lack tumor molecular characteristics, mutations and intra-patient heterogeneity 7-9 . Human HGSC has also been studied using patient-derived xenografts, but these technologies are time and resource-consuming, are poorly suitable for genetic manipulation and drug screening, and experience rapid mouse-specific tumor evolution 7 .Alternatively, knocked-out animals are used, being rodents the most used genetic engineered models of HGSC 10-14 . However, data generated from rodents are not readily translated to the human. First, the mouse does not naturally develop HGSC 15,16 . Secondly, genetically engineered and syngeneic mouse models may not exhibit genetic alterations relevant to human HGSC and, in many instances, may be driven by inappropriate regulatory sequences and promoters 15,16 . Third, cancer phenotypes can vary depending on the mouse strain used to create the cancer model 16 . Fourth, infertility resulting from ovarian tumors has limited the production of transgenic mouse models for ovarian cancer 17 . Nevertheless, the recent advances of the CRISPR-Cas9 system for knocking in and out target genes might offer the same opportunity of gene editing large mammalian species and can specifically increas...

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“…In epithelial tumours of the ovary in dogs the presence of keratins and also desmin was already demonstrated. Desmin positivity was reported by Akihara et al (2007) and this finding was interpreted as proof of the origin of these epithelial tumours from the cells lining the coelomic cavity. In the present case we have observed a reactivity of cytokeratins MNF116 whereas desmin was negative, although there was desmin reactivity in the vascular smooth muscle as an internal control of the immunohistochemical results.…”

Section: Discussionmentioning

confidence: 84%

“…Epithelial tumours of the ovaries have been described in dogs (Sforna et al 2003;Hori et al 2006;Akihara et al 2007), in cattle (Yener et al 2004) and in some other mammals. A similar observation to the reported case was described by Petterino et al (2010) in a bitch.…”

Section: Discussionmentioning

confidence: 99%

Bilateral low grade serous adenocarcinoma of the ovaries in a badger (Meles meles L.) and its association with a borderline serous ovarian tumour: a case report

Kutlvašr¹,

Bukovjan²,

Kodet³

2014

Vet. Med. - Czech

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ABSTRACT:Here, we describe a case of a wild female badger (a sow) with disseminated serous adenocarcinoma of the ovary which corresponds to a group of low grade serous carcinomas of the ovary in humans. Beside grossly apparent dissemination of the disease we observed a scale of histological features classifiable as a precursor lesion -borderline serous tumour of the ovary with implant metastases at the peritoneum, and features of the borderline tumour transformation in the carcinoma. The latter features included invasion of some of the metastatic peritoneal implants into the adipose tissue of the mesentery, retroperitoneum, and in the muscle of diaphragm with lymphangioinvasion and with blood-borne metastatic disease in the lungs. The primary tumour and its metastases had a uniform cytological appearance without atypia of the tumour cells. Mitotic activity was exceptional. The proliferation activity as demonstrated by immunohistochemical investigation of Ki-67 protein expression (revealing all active phases of the cell cycle -G1, S, G2, M) showed a low proliferation activity of the tumour cells, comparable with findings in low grade carcinomas or borderline tumours of the ovaries in women. WT1 protein was expressed in the whole tumour cell population. All these features were diagnostic of serous carcinoma of the ovary with low grade malignant potential. Tumours of the ovaries in wildlife have been described previously but they are infrequent and are rarely classified histopathologically. This case report offers a parallel with serous carcinomas in human pathology including features of transformation from a precursor lesion of a borderline serous tumour into a serous low grade carcinoma.

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Immunohistochemical Evaluation of Canine Ovarian Tumors

Cited by 22 publications

References 15 publications

Activins and Inhibins: Expression and Role in Normal and Pathological Canine Reproductive Organs: A review

Activins and Inhibins: Expression and Role in Normal and Pathological Canine Reproductive Organs: A review

A dog oviduct-on-a-chip model of serous tubal intraepithelial carcinoma

Bilateral low grade serous adenocarcinoma of the ovaries in a badger (Meles meles L.) and its association with a borderline serous ovarian tumour: a case report

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