Molecular portrait-based correlation between primary canine mammary tumor and its lymph node metastasis: possible prognostic-predictive models and/or stronghold for specific treatments?

Abstract

Background: This study aimed to evaluate the relationship between the molecular phenotype of the primary mammary tumor and its related lymph node metastasis in the dog to develop prognostic-predictive models and targeted therapeutic options.

Results: Twenty mammary tumor samples and their lymph node metastases were selected and stained by immunohistochemistry with anti-estrogen receptor (ER), -progesterone receptor (PR), -human epidermal growth factor receptor 2 (c-erbB-2), -cytokeratin 5/6 (CK 5/6), -cytokeratin 14 (CK14), -cytokeratin 19 (CK 19) and -protein 63 (p63) antibodies. Four phenotypes (luminal A, luminal B, c-erbB2 overexpressing and basal-like) were diagnosed in primary tumors and five (luminal A, luminal B, c-erbB-2 overexpressing, basal-like and normal-like) in the lymph node metastases. Phenotypic concordance was found in 13 of the 20 cases (65%), and seven cases (35%) showed discordance with different lymph node phenotypic profile from the primary tumor.

Conclusions: The phenotype of the primary tumor assumes a predictive-therapeutic role only in concordant cases, meaning that both the primary tumor and its lymph node metastasis should be evaluated at the same time. A treatment plan based only on the primary tumor phenotype could lead to therapeutic failures if the phenotype of the lymph node metastasis differs from that of the primary tumor.

Figure 1

Luminal A phenotype: concordant and discordant cases. Line 1: Luminal A concordant case with ER+ and c-erbB-2– (1A, 1B) in the primary tumor and ER+, cerbB-2–, CK14– (1C, 1D, 1E) in the lymph node metastases. Line 2: Discordant case with luminal A phenotype PR+, c-erbB-2– (2A, 2B) in the mammary tumor and progression to basal-like phenotype PR–, c-erbB-2–, CK14+ (2C, 2D, 2E) in the respective nodal metastasis. Line 3: Discordant case presenting in the primary mammary carcinoma luminal A phenotype ER+, c-erbB-2– (3A, 3B) and normal-like phenotype ER–, cerbB-2–, CK5/6– (200x) (3C, 3D, 3E) in the lymph node. 400x.

Figure 2

Luminal B phenotype: concordant and discordant cases. Line 1: Luminal B concordant case with PR+ and c-erbB-2+ (1A, 1B) in theprimary neoplasia and PR+, cerbB-2+, CK14+ (1C, 1D, 1E) in the lymph node metastases. Line 2: Discordant case showing luminal B phenotype PR+, c-erbB-2+ (2A, 2B) in the primary tumor becoming c-erbB-2 overexpressing phenotype in the lymph node PR–, c-erbB-2+, CK5/6+ (2C, 2D, 2E). Line 3: Discordant case with luminal B phenotype ER+, c-erbB-2+ (3A, 3B) in the mammary tumor and progression to basal-like phenotype ER–, c-erbB-2–, CK 14+ (3D, 3E, 3F) in the respective nodal metastasis. Line 4: Discordant case presenting in the primary mammary carcinoma luminal A phenotype ER+, c-erbB-2– (4A, 4B) and normal-like phenotype PR–, cerbB-2–, p63– (4D, 4E, 4F) in the lymph node. 400x.

Figure 3

C-erbB-2 overexpressing phenotype: concordant case. PR–, c-erbB-2+ (1A, 1B) in mammary tumor and PR–, c-erbB-2+, p63– (200x) (2C, 2D, 2E) in the respective lymph node metastasis. 400x.

Figure 4

Basal-like phenotype: concordant case. ER–, c-erbB-2–, CK5/6+ (1A, 1B, 1C) in mammary neoplasia and PR–, c-erbB-2–, CK 14+ (2C, 2D, 2E) in the lymph node metastasis. 400x.