The present study is the first multicenter project regarding associations between DCE MRI and clinically relevant histopathological features in BC.
Previously, the role of DCE MRI was analyzed systematically in prostate cancer, glioma, and squamous cell carcinoma of the head and neck region. In prostate cancer, it was shown that Ktrans values were significantly higher for high-grade versus low-grade lesions . Furthermore, Kep correlated positively with mean blood vessel count and mean vessel area . In glioma, Ktrans and Ve values of grade 2 tumors were significantly lower than those of grade 3 . Moreover, Ktrans and Ve significantly correlated with the KI 67 index . Finally, Ktrans showed a significant positive correlation with VEGF expression in high grade gliomas (r = 0.505, P < 0.001) . Also in head and neck squamous cell carcinomas DCE MRI can predict relevant histopathological features. So far, Ktrans correlated well with expression of Ki 67 and Ve with the mean microvessel diameter .
In BC, only few studies reported data about associations between DCE MRI and histopathology. The published results are promising. For instance, it has been shown that parameters of DCE MRI were different in tumors with different hormone receptor expression and grade. So far, grade 3 cancers had higher Ktrans and Kep values in comparison to grade 1 lesions [12, 13]. Mean Ve was lower in tumors with a high histologic grade than in tumors with a low histologic grade . Regarding expression of hormone receptors, triple negative BC showed higher Ktrans and Kep, but lower Ve values than luminal BC . Furthermore, Ve correlated inversely with HER 2 expression .
Our data showed that HER 2 rich BC had lowest Ktrans and Ve values in comparison to other subtypes. Furthermore, triple negative BC had highest Ktrans values. However, as shown, values of DCE MRI overlapped significantly and, therefore, cannot be used for prediction of hormone receptor status in BC in clinical practice.
Furthermore, our data indicated that DCE MRI parameters did not reflect tumor grade in BC.
Another important aspect in BC is expression of proliferation marker KI 67. It is well known that high expression of KI 67 is associated with a greater risk of death compared with lower expression rates . Therefore, prediction of proliferation potential of BC based on imaging is very important. According to previous reports, parameters of DCE MRI are associated with KI 67 index. However, the reported data are controversial [12, 13, 21, 23]. For example, Kang et al. showed that carcinomas with high expression KI 67 showed statistically significant higher Kep values in comparison to BC with low expression of KI 67 and Ktrans and Ve values did not differ between the tumors . Liu et al. found that only Ktrans correlated with KI 67 . Koo et al. did not observed statistically significant associations between DCE MRI values and KI 67 . Finally, Kim et al. observed significant relationships between Ktrans, Kep and KI 67, but not between Ve and KI 67 . Moreover, the previous studies used different thresholds of KI 67 expression for distinguishing tumors with low and high proliferation activity, namely 15% , 10% , and 5% . In one study two threshold values, 5% and 15% were analyzed . This fact relativizes the reported results. According to a large meta analysis based on data of 64,196 patients, the optimal KI 67 cut-off is 25% .
In the present work, KI 67 correlated statistically significant with all DCE MRI parameters. The strongest correlation was observed with Ktrans (r = 0.44, p = 0.0001). However, the optimal threshold of Ktrans to discriminate BC with high (> 25%) and low (< 25%) expression of KI 67 yielded a relatively low sensitivity (75.5%) and specificity (73.0%), as well as low accuracy (74.0%). Also, this applied for several alternate thresholds of KI 67 expression ranging from 10–50%.
Another important clinical question is, if imaging features of primary tumors can predict occurrence of nodal and/or distant metastases. Previously, it has been indicated that some MRI features of BC were associated with occurrence of nodal metastases . Regarding DCE MRI, presumably, perfusion parameters of primary tumor may be able to predict occurrence of lymph node metastases. In fact, BC with lymphovascular space invasion (LVSI) had higher Ktrans and Kep than tumors without LVSI . Our results, however, did not confirm this hypothesis. Although DCE MRI parameters of BC differed between N0 vs N + stages, all of them overlapped significantly. Therefore, parameters of DCE MRI obtained from primary tumors cannot be used for prediction of nodal stage in BC.
The present multicenter study is the largest to date. However, there are some limitations to address. The involved patients were investigated on different MR scanners with different technical parameters like field strength and other technical parameters. Furthermore, one center acquired patients with BC retrospectively with appropriate bias. Our sample consist predominantly on invasive ductal carcinomas. Therefore, this study could not compare DCE MRI values between different tumor types. Presumably, other types like lobular or mucinous carcinomas may have different DCE MRI parameters than ductal carcinomas.