Lymphatic and Blood Vessels in Basal and Triple-negative Breast Cancers

Characteristics And Prognostic Significance

Rabab AA Mohammed; Ian O Ellis; Ali M Mahmmod; E Claire Hawkes; Andrew R Green; Emad A Rakha; Stewart G Martin

Disclosures

Mod Pathol. 2011;24(6):774-785. 

In This Article

Results

Vascular Characteristics in Basal vs Non-basal Tumour Types and in Triple-negative vs Non-triple-negative Groups

Basal-like and Non-basal-like Tumours Clinicopathological characteristics were compared between the basal-like and the non-basal-like groups. Tumours of the basal-like phenotype were characterised by larger tumour size, high grades and negativity for ER and PR. The associations between the clinicopathological characteristics of the basal-like subtypes, prognosis and difference from luminal subtypes have been the subject of many studies and are reported and discussed in detail elsewhere.[3,5,7,35–37]

Lymph-vessel density in the total study population ranged between 0.00 and 10.57/mm2, with a mean of 2.2±0.16 and a median of 1.43. The lymph-vessel density in the basal group was 2.2±0.16 compared with 1.64±0.14 in the non-basal group with no significant difference (P=0.227). Microvessel density in the total study population ranged from 1 to 6.7, with a mean of 2.73±0.08 and a median of 2.7. Microvessel density was significantly higher in the basal (3.73±0.08) than in the non-basal group (2.60±0.08) (P=0.017). Vascular invasion was detected in 53 (27%) of basal-like specimens and in 21% of non-basal specimens with no significant difference between the two (P=0.159, Table 2). In 50 of the 53 basal-like specimens, invasion was lymphatic vascular invasion, in 2 specimens, the vascular invasion was blood vascular invasion, and in one specimen, there were both lymphatic and blood vascular invasion. In non-basal cases, vascular invasion was detected in 41 of 200 (21%) cases, all of which were lymphatic vascular invasion with no blood vascular invasion being detected.

Triple-negative and Non-triple-negative Tumours The mean lymph-vessel density in the triple-negative group was 2.01±0.16 compared with 1.82±0.09 in the triple-negative group, with no significant difference between the two (P=0.212). Microvessel density was significantly higher in the triple-negative group (3.1±0.12) than in the NT group (2.58±0.06) (P <0.001, Table 3). Vascular invasion was detected in 26 specimens in the triple-negative group, 24 were lymphatic vascular invasion (without blood vascular invasion) and 2 were blood vascular invasion (without lymphatic vascular invasion). Vascular invasion was detected in 73 of 334 (22%) specimens in the non-triple-negative group; 72 of 73 were lymphatic vascular invasion and 1 of 73 was lymphatic vascular invasion with associated blood vascular invasion. The frequency of vascular invasion was higher in the triple-negative group (26%) than (22%) in the non-triple-negative group; however, this was not statistically significant (P=0.359).

Lymph-vessel Density, Microvessel Density and Vascular Invasion in Basal and Triple-negative Phenotypes and their Association with Clinicopathological Characteristics

Basal-like Tumours Basal specimens were categorised into two groups according to the median lymph-vessel density (1.43). There were no significant associations with tumour size, grade or hormonal status or with any of the clinicopathological criteria. Specimens were also categorised into two groups based on the median microvessel density (2.7), 87 (43%) falling into the high microvessel-density category. Such specimens were significantly associated with tumour sizes >1.5 cm (P=0.001), poor differentiation (high grades) (P <0.001), negative ER (P <0.001) and negative PR status (P=0.008). No significant association was detected in relation to recurrence (P=0.138), distant metastasis (P=0.129) or death from the disease (P=0.191, Table 4).

The presence of vascular invasion (both lymphatic and blood vascular invasion) was significantly associated with tumour sizes >1.5 cm (P=0.001), ER-negative specimens (P=0.002), development of recurrence (P=0.045), distant metastasis (P=0.021) and death from the disease (P=0.016, Table 5).

A study for correlations between high lymph-vessel density, high microvessel density and the presence of vascular invasion was conducted to determine whether there were any relationships between the three vascular characteristics in basal-like samples. High lymph-vessel density was not associated with high microvessel density (P=0.116), but was significantly associated with the presence of vascular invasion (P<0.0001). No significant association was found between high microvessel density and the presence of vascular invasion (P=0.533).

Triple-negative Tumours The same analysis was repeated with the triple-negative group, neither lymph-vessel density, microvessel density nor vascular invasion was associated with any clinicopathological features, patient age, tumour size or tumour grade.

Survival Analysis of Lymph-vessel Density, Microvessel Density and Vascular Invasion in Basal-like and Triple-negative Groups

Basal-like Tumours High lymph-vessel density, high microvessel density and the presence of vascular invasion were analysed with 20-year follow-up data using the log-rank test and Kaplan–Meier survival curves. Neither high lymph-vessel density nor high microvessel density was associated with overall survival (P=0.343 and P=0.133, respectively) or with disease-free interval (P=0.628 and P=0.181, respectively).

However, vascular invasion was significantly associated with reduced overall survival and shorter disease-free interval (Figure 2). The 20-year overall survival rate was 55% in specimens having vascular invasion compared with 73% in specimens negative for vascular invasion (P=0.012). Similarly, the 20-year disease-free interval was 25% with the presence of vascular invasion compared with 49% in the absence of vascular invasion (P=0.046, Table 6). In multivariate analysis of vascular invasion for overall survival, tumour grade (P=0.01) and vascular invasion (P=0.044) retained significance. Tumour size and oestrogen receptor status were of borderline significance (P=0.050 and P=0.055, respectively, Table 7). Multivariate analysis for disease-free interval using the same variables showed no significance.

Figure 2.

Survival analysis of vascular invasion (VI), microvessel density (MVD) and lymphatic vessel density (LVD) using Kaplan–Meier survival curves in the basal group. The presence of VI is significantly associated with shorter OS (P=0.012) and with shorter disease-free interval (P=0.046). MVD and LVD have no significant associations with either disease-free interval or overall survival.

Triple-negative Tumours The same analyses, as described above, were conducted on the triple-negative group. Similar to the basal-like group, neither high lymph-vessel density nor high microvessel density was associated with reduced survival (P=0.486 and P=0.865, respectively) or with reduced disease-free interval (P=0.668 and P=0.607, respectively). The presence of vascular invasion was significantly associated with overall survival (P <0.001), but not with disease-free interval (P=0.176, Table 8 and Figure 3). In multivariate analysis, vascular invasion retained significance (P=0.010), whereas size and grade did not (P=0.156 and P=0.997, respectively).

Figure 3.

Survival analysis of vascular invasion (VI), microvessel and lymphatic vessel density using Kaplan–Meier survival curves in the triple-negative group. The presence of VI is significantly associated with shorter overall survival (P=0.001) but not with disease-free interval (P=0.176). Microvessel and lymphatic vessel density have no significant associations with either disease-free interval or overall survival.

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