# Intratumoral CD3+ T-Lymphocytes Immunoexpression and Its Association with c-Kit, Angiogenesis, and Overall Survival in Malignant Canine Mammary Tumors

**Authors:** Maria Isabel Carvalho, Isabel Pires, Marlene Dias, Justina Prada, Hugo Gregório, Luis Lobo, Felisbina Queiroga

PMC · DOI: 10.1155/2015/920409 · 2015-08-05

## TL;DR

This study explores how immune cells and specific proteins in canine mammary tumors relate to tumor aggression and survival.

## Contribution

The study identifies CD3+ T-cells and c-kit/VEGF as independent prognostic factors in malignant canine mammary tumors.

## Key findings

- CD3+ T-cells and c-kit overexpression correlate with VEGF and CD31 in canine mammary tumors.
- High CD3/VEGF, c-kit/VEGF, and CD3/c-kit tumors are linked to higher malignancy and poor prognosis.
- c-kit/VEGF remains a significant independent prognostic factor in multivariate analysis.

## Abstract

In this study 80 malignant CMT were submitted to immunohistochemical detection of CD3, c-kit, VEGF, and CD31, together with clinicopathological parameters of tumor aggressiveness. CD3+ T-cells and c-kit overexpression revealed a positive correlation with VEGF (r = 0.503, P < 0.0001; r = 0.284, P = 0.023 for CD3 and c-kit, resp.) and CD31 (r = 0.654, P < 0.0001; r = 0.365, P = 0.003 for CD3 and c-kit, resp.). A significant association (P = 0.039) and a positive correlation (r = 0.263, P = 0.039) between CD3 and c-kit were also observed. High CD3/VEGF, c-kit/VEGF, and CD3/c-kit tumors were associated with elevated grade of malignancy (P < 0.0001 for all groups), presence of intravascular emboli (P < 0.0001 for CD3/VEGF and CD3/c-kit; P = 0.002 for c-kit/VEGF), and presence of lymph node metastasis (P < 0.0001 for all groups). Tumors with high CD3/VEGF (P = 0.006), c-kit/VEGF (P < 0.0001), and CD3/c-kit (P = 0.002) were associated with poor prognosis. Interestingly high c-kit/VEGF tumors retained their significance by multivariate analysis arising as independent prognostic factor.

## Linked entities

- **Genes:** cd.3 (Cd.3 conserved hypothetical protein) [NCBI Gene 1258599], KIT (KIT proto-oncogene, receptor tyrosine kinase) [NCBI Gene 3815], VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422], PECAM1 (platelet and endothelial cell adhesion molecule 1) [NCBI Gene 5175]

## Full-text entities

- **Genes:** KITLG (KIT ligand) [NCBI Gene 403507] {aka 710-712, CSF, MGF}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 403802] {aka VEGF}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, KITLG (KIT ligand) [NCBI Gene 4254] {aka DCUA, DFNA69, FPH2, FPHH, KL-1, Kitl}, IL12B (interleukin 12B) [NCBI Gene 3593] {aka CLMF, CLMF2, IL-12B, IMD28, IMD29, NKSF}, PECAM1 (platelet and endothelial cell adhesion molecule 1) [NCBI Gene 5175] {aka CD31, CD31/EndoCAM, GPIIA', PECA1, PECAM-1, endoCAM}, KIT (KIT proto-oncogene, receptor tyrosine kinase) [NCBI Gene 403811] {aka c-KIT}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 480348], KIT (KIT proto-oncogene, receptor tyrosine kinase) [NCBI Gene 3815] {aka C-Kit, CD117, MASTC, PBT, SCFR}, PIK3R1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 5295] {aka AGM7, GRB1, IMD36, p85, p85-ALPHA, p85alpha}
- **Diseases:** breast cancer (MESH:D001943), Lymph node metastasis (MESH:D008207), tubulopapillary carcinoma (MESH:D000077779), CMT (MESH:C537989), cutaneous grade III mast cell tumors (MESH:D007946), lymph node (MESH:D000072717), Neoplastic intravascular emboli (MESH:D020766), cancer (MESH:D009369), skin ulceration (MESH:D012883), small cell lung cancer (MESH:D055752), angiosarcoma (MESH:D006394), mammary tumorigenesis (MESH:D063646), metastasis (MESH:D009362), OS (MESH:D011475), anaplastic carcinomas (MESH:D002277), carcinosarcoma (MESH:D002296), CMT (MESH:D015674), sarcoma (MESH:D012509), Chronic inflammation (MESH:D007249),  (MESH:D009389),  (MESH:D004283),  (MESH:D009361)
- **Chemicals:** imatinib (MESH:D000068877), PBS (MESH:D007854), citrate (MESH:D019343), H2O2 (MESH:D006861), water (MESH:D014867), 3,3'-diaminobenzidine tetrahydrochloride (-), formalin (MESH:D005557), Paraffin (MESH:D010232), hematoxylin (MESH:D006416),  (MESH:D042461),  (MESH:D019408),  (MESH:D017252),  (MESH:D019009),  (MESH:D014408)
- **Species:** Homo sapiens (human, species) [taxon 9606], Canis lupus familiaris (dog, subspecies) [taxon 9615]

## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC4540957/full.md

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Source: https://tomesphere.com/paper/PMC4540957