Rate of Apoptosis in Feline Mammary Tumors is not Predictive of Postsurgical Survival

Sarli, Giuseppe; Preziosi, R.; Benazzi, Cinzia; Bazzo, Roberta; Mandrioli, Luciana; Marcato, Paolo Stefano

doi:10.1177/104063870301500205

Cited by 11 publications

(15 citation statements)

References 28 publications

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“…Of note, the REE/LVI grading system was associated with overall survival although 1 of its main parameters (nuclear form) was not significantly associated with overall survival (P ¼ .21). This is probably mainly due to robustness of lymphovascular invasion as a prognostic factor in feline mammary carcinomas in general 19,21,23,28 and in our cohort more specifically. Although valuable prognostically, lymphovascular invasion represents a main weakness of this grading system because it refers to the histological stage of feline mammary carcinomas (ie, the extent of cancer within the host) rather than to the histological grade (which is a reflection of cancer cell differentiation, proliferation, and atypia).…”

Section: Discussionmentioning

confidence: 72%

Feline Invasive Mammary Carcinomas: Prognostic Value of Histological Grading

et al. 2019

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Feline mammary carcinomas are highly malignant tumors usually associated with poor outcome. Nevertheless, survival times can differ significantly according to various prognostic factors. The Elston and Ellis (EE) histologic grading system, originally developed for human breast cancer, is commonly used to grade feline mammary carcinomas, although it is not really adapted for this species, hence the need of a more relevant grading system. Although few veterinary studies attempted to validate previously published results in an independent cohort, the aim of our study was to evaluate the prognostic value of different histologic grading systems in feline invasive mammary carcinomas, including the EE grading system applicable to human breast cancers and the modified and newly designed histologic grading systems recently proposed by Mills et al. Survey data and histologic features of 342 feline invasive mammary carcinomas were analyzed with respect to overall and cancer-specific survival. The histological grading system with best prognostic value was the mitotic-modified Elston and Ellis (MMEE) grading system: grade III carcinomas ( P = .04, hazard ratio [HR] = 1.46, 95% CI, 1.01–2.11), grade II ( P = .03, HR = 1.39, 95% CI, 1.03–1.88), and grade I carcinomas (HR = 1.00, reference), with decreasing hazard ratios significantly were associated with a worse overall survival, independently from the pathologic tumor size (pT ≥ 20 mm: P = .002, HR = 1.45, 95% CI, 1.15–1.83) and positive nodal stage ( P = .001, HR = 1.51, 95% CI, 1.18–1.94). This retrospective study validates Mills et al’s proposal to adapt the thresholds for mitotic counts to better assess the histological grade of the highly proliferative mammary carcinomas encountered in the cat.

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Section: Discussionmentioning

confidence: 72%

Feline Invasive Mammary Carcinomas: Prognostic Value of Histological Grading

et al. 2019

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“…2). Moreover, for the 30 cats that underwent 16.7% (¯ve out of 30) died from non-tumor-related diseases, and 10% (three out of 30) had unknown outcomes due to lack of further information. However, 50% (15 out of 30) of the cats¯nally died from distant metastasis, and the mean and median intervals prior to detection of distant metastatic disease were 139 days and 101 days, respectively.…”

Section: Survival Curves Associated With Clinical Factorsmentioning

confidence: 99%

“…10,13 Lymphovascular invasion was also associated with shorter OST. 11,[14][15][16] Histological grade was one of the factors mostly associated with survival in cats with FMCs. A previous study reported that grading of FMCs was associated with one-year post-surgical outcomes in grade-1(leading to 0% death), grade-2 (42.4% death) and grade-3 (100%) tumors.…”

Section: Introductionmentioning

confidence: 99%

With Surgical Removal or Adjuvant Chemotherapy Increase the Two-Year Survival and Associated Clinicopathologic Factors in Cats With Mammary Carcinomas

Feng

Yang

et al. 2019

Taiwan Vet J

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Due to the aggressive biological behavior, a large number of studies attempt to identify the prognostic indicators for feline mammary carcinoma (FMC). In this study, we retrospectively identified the prognostic indicators and evaluated the effect of surgery with or without adjuvant chemotherapy on 47 cats with FMCs. Over a two-year follow-up period, surgical removal was significantly associated with greater overall survival time (OST). In cats that underwent surgical treatment, median OST was longer in cats that underwent surgery with adjuvant chemotherapy (540 days) than cats that underwent surgery without chemotherapy (398 days). In addition, cats with FMCs in early stage (I or II) had longer OST than cats in advanced stages. Further, through multivariate analyses, the histological grade was found to be significantly associated with a survival of two years. Cats with FMCs at high grade were most likely to have a mean or median OST of less than one year. In summary, stage, grade and the size of tumor were all prognostic factors, in which histological grade was found to be the only significant factor in cats with mammary carcinomas through multivariate analysis.

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“…The overall survival time can vary significantly depending on the tumor size [1, 4–6], World Health Organization stage [5, 6], histologic grade [1], tumor subtype [1], nuclear pleomorphism [1] and lymphovascular invasion [1, 5, 6]. Increased expression of vascular endothelial growth factor, estrogen receptor (ER), progesterone receptor, AKT [7], epidermal growth factor receptor 2 (HER-2) [8, 9], cyclooxygenase-2 [10, 11], Ki-67 [5, 12, 13] and p53 mutations [14, 15] have been investigated to identify prognostic molecular markers of FMTs, but only a few markers have entered clinical use. Therefore, a more appropriate therapeutic target is needed to improve the understanding and biological characterization of FMTs and therapeutic development.…”

Section: Introductionmentioning

confidence: 99%

Significance of sphingosine kinase 1 expression in feline mammary tumors

et al. 2019

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Background Sphingosine kinase 1 (SPHK1) is an enzyme that converts pro-apoptotic ceramide and sphingosine into anti-apoptotic sphingosine-1-phosphate. There is growing evidence that SPHK1 activation promotes oncogenic transformation, tumor growth, chemotherapy resistance, and metastatic spread. High SPHK1 expression has been associated with a poor prognosis in several human cancers. Results In the present study, the expression level of SPHK1 was examined in feline mammary tumor (FMT) specimens, and the IHC expression level of SPHK1 was associated with the histological grade of FMTs. IHC analysis of 88 FMT cases revealed that the expression level of SPHK1 was upregulated in 53 tumor tissues (60.2%) compared to adjacent mammary tissues. SPHK1 expression in FMTs was significantly associated with histological grade, presence of lymphovascular invasion, and estrogen receptor negativity. Treatment of primary FMT cells with SPHK1 inhibitors reduced cell viability, indicating that SPHK1 acts to promote FMT cell survival. These results indicate that SPHK1 may play an important role in FMTs and may be a therapeutic target in cats with FMT. Conclusions SPHK1 over-expression in breast cancer tissues is associated with a poor prognosis in humans. SPHK1 over-expression in more aggressive FMTs provides support for a potential role of SPHK1 inhibitors for the treatment of FMTs. Targeting SPHK1 has potent cytotoxic effects in primary FMT cells. These findings suggest that further examination of the role SPHK1 plays in FMTs will pave the way for the investigation of SPHK1 inhibitors in future clinical applications. Electronic supplementary material The online version of this article (10.1186/s12917-019-1883-z) contains supplementary material, which is available to authorized users.

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Rate of Apoptosis in Feline Mammary Tumors is not Predictive of Postsurgical Survival

Cited by 11 publications

References 28 publications

Feline Invasive Mammary Carcinomas: Prognostic Value of Histological Grading

Feline Invasive Mammary Carcinomas: Prognostic Value of Histological Grading

With Surgical Removal or Adjuvant Chemotherapy Increase the Two-Year Survival and Associated Clinicopathologic Factors in Cats With Mammary Carcinomas

Significance of sphingosine kinase 1 expression in feline mammary tumors

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