The prognostic significance of immunophenotypes in canine malignant mammary tumors

Nunes, Fernanda Camargo; Bertagnolli, Angélica Cavalheiro; Lavalle, Gleidice Eunice; Silveira, Tatiany L.; Balabram, Débora; Cassali, Geovanni Dantas

doi:10.1590/1678-4162-12273

Cited by 3 publications

(1 citation statement)

References 18 publications

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“…Establishment of immunophenotype for cIMPC followed that proposed by Nunes ( 67 ), which classifies tumors as Luminal A (ER or PR +, HER2 – and Ki67 <20%), Luminal B (ER or PR +, HER2 – and Ki67 >20%), Luminal B HER2+ (ER or PR +, HER2 + and any Ki67), HER2 (ER -, PR -, HER2 +, any Ki67) or Triple-Negative (ER -, PR -, HER2 - and any Ki67). Similarly, the immunophenotype for hIMPC followed that proposed in St. Gallen International Breast Cancer Conference Expert Panel ( 68 , 69 ), which considers Luminal A (ER +, PR + ≥20%, HER2 - and Ki67 <14%), Luminal B (ER +, PR <20% or Ki67 >14%, and HER2 -), Luminal B HER2+ (ER +, any PR, HER2 + and any Ki67), HER2 (ER -, PR -, HER2 + and any Ki67), and Triple-Negative (ER -, PR -, HER2 – and any Ki67).…”

Section: Methodsmentioning

confidence: 99%

COX-2 expression in mammary invasive micropapillary carcinoma is associated with prognostic factors and acts as a potential therapeutic target in comparative oncology

et al. 2022

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Pure human and canine mammary invasive micropapillary carcinoma is a rare malignant epithelial tumor accounting for 0.9 to 2% of all invasive mammary carcinomas and present a high rate of lymphatic invasion and metastasis, with unfavorable prognosis. Surgery and chemotherapy are standard treatments for almost all mammary cancer in both species, as well as hormonal and target therapies available for human patients. However, depending on the patient's clinical staging, satisfactory therapeutic results for invasive micropapillary carcinoma are a challenge due to its high capacity of invasion and metastasis. Cyclooxygenase-2 (COX-2) isoform is an important enzyme stimulated by cytokines, growth factors and oncogenes activation to synthetizes prostaglandins in inflammatory process. COX-2 overexpression is associated with angiogenesis and invasion and contributes to cancer development, disease progression, tumor recurrence and regional lymph node metastasis in human and canine mammary carcinomas. This enzyme can be targeted by non-steroidal anti-inflammatory drugs and its inhibition can reduce tumor growth and metastasis in several cancer types. Given the similarity between both species, the present study aims to elucidate the involvement of COX-2 mRNA and protein expression in canine (cIMPC) and human (hIMPC) pure invasive mammary micropapillary carcinoma, with clinicopathological and survival data. Twenty-nine cases of cIMPC and 17 cases of hIMPC were analyzed regarding histologic type, grade, age, tumor size, lymph node condition, extracapsular extension, inflammatory infiltrate and immunophenotype. When available, information on adjuvant treatment, recurrence, metastasis and overall survival were collected. The present study demonstrated COX-2 protein expression in 65.5% of cIMPC and 92.3% of hIMPC, and an association with more advanced histological grades in bitches and higher Ki67 in women. COX-2 mRNA expression was significantly higher in cIMPC than in hIMPC, and its expression was not associated with COX-2 protein expression in both species. COX-2 mRNA expression was associated with negative-ER hIMPC as well as higher Ki67. cIMPC demonstrated proportional early development, more regional metastasis, and a prevalence of negative estrogen receptor, than hIMPC. This is the first time COX-2 expression is associated with negative prognostic factors in both cIMPC and hIMPC, besides the overexpression of COX-2 protein in such unfavorable histological type, which suggests that COX-2 can act as a potential target in IMPC.

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Section: Methodsmentioning

confidence: 99%

COX-2 expression in mammary invasive micropapillary carcinoma is associated with prognostic factors and acts as a potential therapeutic target in comparative oncology

et al. 2022

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Risk factor analysis and clinicopathological characteristics of female dogs with mammary tumours from a single-center retrospective study in Poland

Dolka,

Czopowicz,

Stopka

et al. 2024

Sci Rep

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This is a comprehensive retrospective study to characterize female dogs with canine mammary tumors (CMTs) using a dataset retrieved from the archives of the Division of Animal Pathology, Institute of Veterinary Medicine in Warsaw, and to identify prognostic factors. Clinical and histopathological data of 1447 dogs with CMTs were included. Malignant tumours were found in 83.3% (n = 1206), benign tumours in 11.7% (n = 169), and non-neoplastic lesions in 5.0% (n = 72) of dogs. Dogs most often had grade II carcinomas (38.2%, 215/562) of a single histological subtype (88.5%, 1281/1447), mostly simple carcinoma (35.3%, 510/1447). Dogs with a median age of 10 years significantly often had larger (≥ 3 cm) and malignant CMTs, whereas intact females had smaller tumours (median size 2.0 cm). However, the threshold value for the age of the dog in the differentiation of malignant and non-neoplastic/benign masses could not be determined. Most females were hormonally active (76.4%, 372/487). Hormonally active dogs significantly more often had multiple tumours. Multiple tumours were significantly smaller (median 2.5 cm) than single ones. Among pedigree dogs, small-breed dogs were mostly recorded (43%, 428/1006). Twelve breeds had an increased risk of CMTs, regardless of tumour behaviour, compared with the theoretical distribution of pedigree dogs in Poland. Four breeds were often affected only by malignant and other four breeds only by non-neoplastic/benign CMT. Large-breed dogs were significantly younger and affected by larger CMT (median 4 cm) compared with small- and medium-breed dogs. Ninety dogs with a malignant CMT and complete records were included in the full analysis of CMT-specific survival (CMT-SS) with a median follow-up time of 20.0 months. We showed that the timing of ovariohysterectomy in relation to mastectomy was significantly associated with grade, CMT-SS, and CMT-related death. We indicated the low diagnostic accuracy of palpation of regional lymph nodes (RLN) in the prediction of their metastatic involvement. By multivariable analysis, dogs with neoplastic emboli, tumour ulceration, and simple or complex carcinoma had a significantly higher risk of local recurrence. Tumour size > 3 cm was as a strong independent predictor of lung metastases. Compared with dogs with an easily separated localized tumour, dogs with a multiple/diffuse malignant CMT pattern had a fivefold higher risk of death. The risk of death was significantly higher in the presence of neoplastic emboli (~ fivefold) and tumour ulceration (~ fourfold). Furthermore, the presence of neoplastic emboli and large tumour size were independent predictors of CMT-related death.

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Collagen modifications predictive of lymph node metastasis in dogs with carcinoma in mixed tumours

Garcia,

Taborda,

Reis

et al. 2024

Front. Vet. Sci.

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IntroductionMixed tumours in the canine mammary gland are the most common histological type in routine diagnosis. In general, these neoplasms have a favourable prognosis that does not evolve into metastatic disease. However, some cases develop into lymph node metastases and are associated with worse patient survival rates.MethodsHere is a retrospective study of 46 samples of primary mixed tumours of the canine mammary gland: 15 cases of benign mixed tumours (BMT), 16 cases of carcinoma in mixed tumours without lymph node metastasis (CMT), and 15 cases of carcinomas in mixed tumours with lymph node metastasis (CMTM). In addition, we selected 23 cases of normal mammary glands (NMT) for comparison. The samples were collected from biopsies performed during nodulectomy, simple mastectomy, regional mastectomy, or unilateral/bilateral radical mastectomy. We used multiphoton microscopy, second harmonic generation, and two-photon excited fluorescence, to evaluate the characteristics of collagen fibres and cellular components in biopsies stained with haematoxylin and eosin. We performed Ki67, ER, PR, and HER-2 immunostaining to define the immunophenotype and COX-2. We showed that carcinomas that evolved into metastatic disease (CMTM) present shorter and wavier collagen fibres as compared to CMT.Results and discussionWhen compared to NMT and BMT the carcinomas present a smaller area of fibre coverage, a larger area of cellular coverage, and a larger number of individual fibres. Furthermore, we observed a correlation between the strong expression of COX-2 and a high rate of cell proliferation in carcinomas with a smaller area covered by cell fibres and a larger number of individual fibres. These findings highlight the fundamental role of collagen during tumour progression, especially in invasion and metastatic dissemination.

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The prognostic significance of immunophenotypes in canine malignant mammary tumors

Cited by 3 publications

References 18 publications

COX-2 expression in mammary invasive micropapillary carcinoma is associated with prognostic factors and acts as a potential therapeutic target in comparative oncology

COX-2 expression in mammary invasive micropapillary carcinoma is associated with prognostic factors and acts as a potential therapeutic target in comparative oncology

Risk factor analysis and clinicopathological characteristics of female dogs with mammary tumours from a single-center retrospective study in Poland

Collagen modifications predictive of lymph node metastasis in dogs with carcinoma in mixed tumours

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