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. 2024 Feb 1:11:1292852.
doi: 10.3389/fvets.2024.1292852. eCollection 2024.

Canine soft tissue sarcomas: the expression of RUNX2 and karyopherin alpha-2 in extraskeletal (soft tissues) and skeletal osteosarcomas

Leonardo Leonardi  1 , Elisabetta Manuali  2 , Antonello Bufalari  1 , Ilaria Porcellato  1
Affiliations

Canine soft tissue sarcomas: the expression of RUNX2 and karyopherin alpha-2 in extraskeletal (soft tissues) and skeletal osteosarcomas

Leonardo Leonardi et al. Front Vet Sci. .

Abstract

Extraskeletal osteosarcoma (EOS) is a malignant tumor producing bone matrix and/or chondroid material, without direct attachment to bone or periosteum. In humans and dogs, EOS is highly infiltrating, rapidly growing, often characterized by osteoid deposition and variable ossification, similar to primary skeletal osteosarcoma (SOS). In dogs, EOS arises from visceral and soft tissue locations, occasionally in trauma or foreign body sites, or in granulomas. Few data are currently available on the phenotype of these tumors. The present study aims to assess the expression RUNX2 and Karyopherin alpha-2 in EOS, comparing it with SOS and the data available from the human counterpart. Seventeen cases of canine osteosarcoma (13 EOS and 4 SOS) were retrospectively selected and submitted to immunohistochemistry for RUNX2 and Karyopherin alpha-2. Our results showed that, in EOS, RUNX2 is expressed in a mean of 73.07 ± 5.36 neoplastic cell nuclei, in face of a mean 36.15 ± 6.25 of Karyopherin alpha-2 positive nuclei. Osteoclasts, when present, were negative for both markers. No correlation was observed among the two markers (p > 0.05), nor statistically significant difference in quantitative expression was assessed comparing EOS and SOS groups. RUNX2 is expressed in canine EOS similarly to SOS and could be used as a diagnostic marker in a larger panel. Karyopherin alpha-2 is expressed in canine EOS and SOS similarly to human SOS and could be validated in future studies as an additional diagnostic marker. Further studies should be planned to evaluate the expression of these proteins as prognostic predictive parameters.

Keywords: canine; diagnostic tools; extraskeletal osteosarcoma; immunohistochemistry; skeletal osteosarcoma; soft tissue sarcoma.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
(A) Extraskeletal osteoblastic osteosarcoma (mammary gland), with abundant osteoid production. Osteoclasts were invariably negative for RUNX2 (arrowheads; 400x, HE); (B) Skeletal fibroblastic osteosarcoma (intrabdominal); the nuclear expression of karyopherin alpha2 is usually maintained in neoplastic cells during mitosis (arrowheads; 400x; AEC and hematoxylin). (C) Extraskeletal chondroblastic osteosarcoma (mammary gland), RUNX2 was not expressed in cells embedded in areas of chondroblastic differentiation (asterisk). (D) Extraskeletal chondroblastic osteosarcoma (mammary gland), karyopherin alpha 2 was not expressed in cells embedded in areas of chondroblastic differentiation (asterisk).
Figure 2
Figure 2
(A) Extraskeletal osteoblastic osteosarcoma (mammary gland). Immunostaining for RUNX2 shows a high percentage of positive nuclei (400x; AEC and hematoxylin). (B) Extraskeletal osteoblastic osteosarcoma (mammary gland). The same area as in (A) shows a lower percentage of positive nuclei for karyopherin alpha 2. (C) Extraskeletal moderately productive osteoblastic osteosarcoma (mammary gland). RUNX2-positive cells were more frequently localized around areas of osteoid deposition (asterisk). (D) Extraskeletal moderately productive osteoblastic osteosarcoma (mammary gland). The distribution of karyopherin alpha 2 is irregular and scattered among neoplastic cells, not associated with osteoid deposition (asterisk).
Figure 3
Figure 3
RUNX2′s modulations to hallmarks of cancer [modified from Lin (10)] and dysregulation of KPNA2 (overexpression) in promoting cancer cells [modified from Han and Wang (17)].
See this image and copyright information in PMC

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