Evaluation of prognostic factors and survival rates in malignant feline mammary gland neoplasms

Abstract

Objectives: The aim of the study was to investigate prognostic factors in feline mammary gland neoplasms, correlating them with overall survival (OS).

Methods: Fifty-six primary malignant mammary gland neoplasms and 16 metastatic lymph nodes from 37 female cats were analyzed. Clinical staging, histologic type and grade, and immunohistochemistry for Ki-67, progesterone and estrogen receptor, human epidermal growth factor receptor type 2 (HER-2), cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) were evaluated. Follow-up was performed in order to correlate prognostic factors with OS.

Results: Lymph node metastasis was found in 35% of cases. Clinical stage III, tubulopapillary carcinomas and histologic grade II cases prevailed in the study. Most neoplasms were positive for hormonal receptors, negative for HER-2 overexpression and presented VEGF overexpression. Immunoreactivity for Ki-67 (P = 0.046) and COX-2 (P = 0.007) was higher in metastases than in primary tumors. COX-2 (P = 0.089), HER-2 (P = 0.012) and histologic grade (P = 0.080) were correlated with OS.

Conclusions and relevance: The data suggest that inhibition of ovarian hormones and COX-2 may represent a therapeutic option for malignant feline mammary gland neoplasms. When evaluating disease progression, COX-2 scores and Ki-67 index should be analyzed in primary tumors and metastases. Histologic grade, HER-2 status and COX-2 scores were found to have a direct influence on OS. Prognostic factors allow for a better understanding of disease outcome in a condition that is characterized by a poor prognosis. The present work highlights the need for further studies on endocrine therapy and COX-2 inhibitors, which could influence OS.

Figure 1

Histopathological and immunohistochemical analysis of malignant feline mammary gland neoplasms. (a) Feline lymph node. Regional metastasis composed of epithelial cells (*). Hematoxylin and eosin (HE), × 40. (b) Feline mammary gland. Tubulopapillary carcinoma presenting an epithelial proliferation in a tubular and papillary pattern. HE, × 40. (c) Feline mammary gland. Cribriform carcinoma presenting an epithelial proliferation in a cribriform pattern. HE, × 40. (d) Feline mammary gland. Tubulopapillary carcinoma presenting neoplastic Ki-67-immunoreactive epithelial cells stained in brown (nuclei) (arrows). Polymeric detection system anti-Ki-67, counterstained with Harris’s hematoxylin (HH), × 60. (e) Feline mammary gland. Tubulopapillary carcinoma presenting neoplastic estrogen receptor (ER)-immunoreactive epithelial cells stained in brown (nuclei) (arrows). Polymeric detection system anti-ER, counterstained with HH, × 60. (f) Feline mammary gland. Tubulopapillary carcinoma presenting neoplastic progesterone receptor-immunoreactive epithelial cells stained in brown (nuclei) (arrows). Polymeric detection system anti-PR, counterstained with HH, × 60

Figure 2

Immunohistochemical analysis of malignant feline mammary gland neoplasms. (a) Feline mammary gland. Tubulopapillary carcinoma presenting neoplastic human epidermal growth factor receptor type 2 (HER-2)-immunoreactive score 1+ epithelial cells stained in brown (membrane). Polymeric detection system anti-HER-2, counterstained with Harris’s hematoxylin (HH), × 40. (b) Feline mammary gland. Tubulopapillary carcinoma presenting neoplastic HER-2-immunoreactive score 3+ epithelial cells stained in brown (membrane polymeric detection system anti-HER-2), counterstained with HH, × 40. (c) Feline mammary gland. Tubulopapillary carcinoma presenting neoplastic low cyclooxygenase (COX)-2-immunoreactive epithelial cells stained in brown (cytoplasm). Polymeric detection system anti-COX-2, counterstained with HH, × 40. (d) Feline mammary gland. Tubulopapillary carcinoma presenting neoplastic high COX-2-immunoreactive epithelial cells stained in brown (cytoplasm). Polymeric detection system anti-COX-2, counterstained with HH, × 40. (e) Feline mammary gland. Tubulopapillary carcinoma presenting neoplastic vascular endothelial growth factor (VEGF)-immunoreactive score 1 epithelial cells stained in brown (cytoplasm). Polymeric detection system anti-VEGF, counterstained with HH, × 40. (f) Feline mammary gland. Tubulopapillary carcinoma presenting neoplastic VEGF-immunoreactive score 3 epithelial cells stained in brown (cytoplasm). Polymeric detection system anti-VEGF, counterstained with HH, × 40

Figure 3

Overall survival curves for 20 queens according to cyclooxygenase (COX)-2 immunohistochemical staining. Thirteen cats had low COX-2 score neoplasms and seven had high COX-2 score neoplasms (P = 0.089)

Figure 4

Overall survival curves for 18 queens according to human epidermal growth factor receptor type 2 (HER-2) immunohistochemical staining. Thirteen cats had HER-2 neoplasms with a score of 1+; three cats had HER-2 neoplasms with a score of 2+; and two cats had HER-2 neoplasms with a score of 3+ neoplasms (P = 0.012)

Figure 5

Overall survival curves for 19 female cats according to histologic grade. Five queens had grade I neoplasms; eight had grade II neoplasms; and six had grade III neoplasms (P = 0.080)