Multiparametric survival analysis of histological stage and proliferative activity in feline mammary carcinomas

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

doi:10.1016/s0034-5288(02)00042-5

Cited by 33 publications

(47 citation statements)

References 30 publications

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“…It was evident in this and previous studies, however, that survival times in affected cats are variable, with postsurgical survival extending for years rather than months in many cases. 19,29,36 Findings of this study support the use of modified EE grading systems or a novel grading system to improve the prognostic value of histologic grading for feline mammary carcinoma.…”

Section: Discussionmentioning

confidence: 57%

“…26 Although feline mammary carcinomas tend to be biologically aggressive, survival times can vary significantly. 19,29,36 Prognosis in affected cats has been shown previously to be influenced by tumor diameter, 14,16,36,38,39 World Health Organization (WHO) stage and modified WHO stage, 14,34 extent of surgery, 16,25 and histologic grade. 4,34 The Elston and Ellis (EE) histologic grading system (also known as the Nottingham Grading System) has been widely adopted by veterinary investigators for the grading of feline mammary carcinoma.…”

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confidence: 99%

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Prognostic Value of Histologic Grading for Feline Mammary Carcinoma

et al. 2014

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Feline mammary carcinoma is highly malignant and generally associated with a poor prognosis, although studies suggest the range of survival times in affected cats is broad. Histologic grading of these tumors is achieved using the Elston and Ellis system, originally developed for human breast cancer. In cats, however, classification using this method has variable prognostic value. Therefore, objectives of this study were (1) to evaluate the Elston and Ellis grading system for feline mammary carcinoma in a predominantly spayed population and (2) to determine whether modification of this system or development of a novel system improved the prognostic value of histologic grading. Survey data and histologic features for 108 carcinomas from 97 cats were analyzed with respect to overall survival. Elston and Ellis grading failed to correlate significantly with overall survival. Using multivariable analysis, lymphovascular invasion, nuclear form, and mitotic count each demonstrated independent prognostic significance (P ¼ .008, <.001, and .004, respectively). Modifications of the Elston and Ellis system and a novel grading system were proposed based on these results; all showed significant correlation with overall survival (P < .001). Median survival times were 27, 29, or 31 months for grade I; 14, 12, or 14 months for grade II; and 13, 5, or 8 months for grade III carcinomas using the mitotic-modified Elston and Ellis, the revised Elston and Ellis, or the novel grading system, respectively. Based on this retrospective study, adoption of the species-specific systems as proposed here may improve the prognostic value of histologic grading for feline mammary carcinoma.

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Section: Discussionmentioning

confidence: 57%

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Prognostic Value of Histologic Grading for Feline Mammary Carcinoma

et al. 2014

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“…5 In veterinary medicine, although the Ki-67 index has been investigated as a prognostic factor in FMC, few data are available on how the Ki-67 index correlates with lower survival. 23,32,37 Furthermore, the evaluation of cell proliferation by Ki-67 immunostaining has not been subject to standardization of protocols. The lack of clear indication on a cutoff level explains why no values have been validated for FMC.…”

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Ki-67 as a Prognostic Factor in Feline Mammary Carcinoma

et al. 2015

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Ki-67 is a nuclear protein and a proliferation marker frequently used in establishing the prognosis for breast cancer patients. To investigate the prognostic value of the Ki-67 proliferation index in female cats with mammary carcinoma, a prospective study was conducted with 96 animals. The Ki-67 index of primary tumors (n ¼ 96) was initially determined, and whenever possible, the Ki-67 index of regional lymph node metastasis (n ¼ 38) and distant metastasis (n ¼ 16) was also estimated. The optimal cutoff value for the Ki-67 index was determined by univariate and multivariate analysis. Ki-67 indices 14% were detected in 72.9% (70 of 96) of the tumors. Tumors with a Ki-67 index 14% were significantly associated with large size (P ¼ .022), poor differentiation (P ¼ .009), presence of necrotic areas (P ¼ .008), estrogen receptor-negative status (P < .0001), fHER2-negative status (P ¼ .003), and shorter overall survival (P ¼ .012). Moreover, Ki-67 expression in the primary tumor was strongly and positively correlated with both regional metastasis (P < .0001; r ¼ 0.83) and distant metastasis (P < .0001; r ¼ 0.83), and was significantly higher in distant metastases when compared with the primary tumor (P ¼ .0009). A similar correlation was also observed between regional and distant metastasis (P < .0001; r ¼ 0.75). On the basis of the above results, the authors propose the adoption of the 14% value as the optimal cutoff for Ki-67 to identify tumors with high risk of disease progression.Keywords feline mammary carcinoma, Ki-67 proliferation index, prognostic factor, cutoff value Feline mammary carcinomas (FMCs) are among the most prevalent tumors in cats, with an incidence that can reach 40% of all tumor cases in this species. 23,39,42 Contrary to those of humans and dogs, 85% to 93% of feline mammary tumors are considered malignant, and the most common histotypes are the tubular, papillary, solid, and cribriform carcinomas. 39 Feline mammary tumors may metastasize to the regional lymph nodes, lungs, and liver, as well as other organs. Although some studies correlate age, tumor size, presence of regional metastasis, and malignancy grade with overall survival (OS), 19,37,43 still scarce information is available regarding the proliferation index of FMC. Based on this scenario, additional prognostic and predictive factors may provide useful insights into tumor biology to achieve a more efficient therapy and a better follow-up of the affected female cats.Ki-67 is a protein found only in growing, dividing cells. It is expressed in all cell cycle phases, except in the resting phase (G0). With an intranuclear localization, the expression levels of Ki-67 are low during the G1 and S phases, rapidly increase during the G2 phase, and reach a peak in mitosis. This well-defined expression pattern makes the Ki-67 antigen a good proliferation marker, very useful and reliable in the prognosis of human breast cancer. 9,45 Several studies of women demonstrated that high Ki-67 expression is a poor prognostic indicator of 5-year rec...

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“…(Gilberston et al 1983). Ce système a été modifié pour être transposé au carcinome mammaire chez la chatte et correspond maintenant à la seule gradation histologique (Preziosi et al 2002) En médecine humaine, une invasion lymphovasculaire augmente, très significativement et respectivement de 1,6 et 5,1 fois, le risque de décès des patientes dont le cancer est de stade pT1N0M0 ou pT2N0M0 (5) (Rakha et al 2012): le risque de mortalité déduit de la présence de LVI est équivalent à celui résultant d'une augmentation de la taille de la tumeur (pT1 à pT2) (Rakha et al 2012). Il semble ainsi que l'apport pronostique de l'embolisation lymphovasculaire soit particulièrement crucial pour les carcinomes mammaires sans métastase ganglionnaire ni métastase à distance ; la LVI peut donc être utilisée pour stratifier, au sein du groupe N0M0, les carcinomes à risque de progression et de mortalité faible ou élevé, comme le préconise le consensus de St Gallen (Goldhirsch et al 2007).…”

Section: Perspectives Concernant La Valeur Pronostique De L'embolisatunclassified

“…Il est alors nécessaire de connaître les facteurs pronostiques afin de prévenir le devenir du patient et de mettre en place un plan thérapeutique adapté. Ceux utilisés dans le pronostic du cancer du sein sont également connus dans l'espèce féline : la taille tumorale (MacEwen et al 1984 ;Ito et al 1996 ;Viste et al 2002 ;Millanta et al 2005 a;Seixas et al 2011), la présence ou non de métastases ganglionnaires ou à distance (Weijer et al 1983 ;Ito et al 1996 ;Seixas et al 2011, Zapulli et al 2014, le type et le grade histologique du carcinome (Weijer et al 1983 ;Ito et al 1996 ;Castagnaro et al 1998 ;Millanta et al 2002 ;Seixas et al 2011 ;Segonzac, 2013 ;Zapulli et al 2014), le caractère complet de l'exérèse chirurgicale (Weijer et al 1983), le score d'expression du facteur de croissance épidermique de type 2 (HER2) (Millanta et al 2005b ;Rasotto et al 2011), l'expression des récepteurs des oestrogènes et de la progestérone (Millanta et al 2005b ;Millanta et al 2006) et l'invasion lymphovasculaire (Seixas et al 2011 ;Preziosi et al 2002 ;Tanabe et al 2002 ;Sarli et al 2003;Zapulli et al 2014).…”

Section: Introductionunclassified

Emboles lymphatiques des carcinomes mammaires invasifs félins : amélioration de leur détection par immunohistochimie et valeur pronostique

Besnard¹

2016

bavf

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Notre étude rétrospective avec suivi clinique de 350 chattes a pour objectifs de déterminer la fréquence de l'embolisation lymphatique et sa corrélation avec les autres caractéristiques du carcinome mammaire invasif félin, de valider un marqueur immunohistochimique d'aide à la mise en évidence des emboles lymphatiques et de déterminer s'il améliore la prédiction pronostique. Nos résultats indiquent que l'invasion lymphovasculaire concerne 41% des carcinomes mammaires, notamment ceux de grande taille et/ou de haut grade et/ou négatifs pour le récepteur à la progestérone. L'embolisation lymphatique est un facteur pronostique fort lié au risque de généralisation métastatique et de décès lié au cancer. Dans près de 8% des cas, les coupes histologiques colorées par l'hémalun-éosine-safran (HES) ne permettent pas de statuer avec certitude sur sa présence. Le marqueur LMO2 (LIM-only domain protein-2), spécifique de l'endothélium lymphatique, permet de reclasser les cas douteux et participe à prédire le risque de décès des chattes à court terme après l'exérèse chirurgicale du carcinome. Mots

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Multiparametric survival analysis of histological stage and proliferative activity in feline mammary carcinomas

Cited by 33 publications

References 30 publications

Prognostic Value of Histologic Grading for Feline Mammary Carcinoma

Prognostic Value of Histologic Grading for Feline Mammary Carcinoma

Ki-67 as a Prognostic Factor in Feline Mammary Carcinoma

Emboles lymphatiques des carcinomes mammaires invasifs félins : amélioration de leur détection par immunohistochimie et valeur pronostique

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