Abstract
Colorectal carcinoma (CRC) is the third most common cancer. Likewise, it is a disease that has a long survival if it is prematurely detected. However, more than 50% of patients will develop metastases, mainly in the liver (LM-CRC), throughout the evolution of their disease, which accounts for most CRC-related deaths. Treatment it is certainly a controversial issue, since it has not been shown to increase overall survival in the adjuvant setting, although it does improve disease free survival (DFS). Moreover, current chemotherapy combinations are administered based on data extrapolated from primary tumors (PT), not considering that LM-CRC present a very particular tumor microenvironment that can radically condition the effectiveness of treatments designed for a PT. The liver has a particular histology and microenvironment that can determine tumor growth and response to treatments: double blood supply, vascularization through fenestrated sinusoids and the presence of different mesenchymal cell types, among other particularities. Likewise, the liver presents a peculiar immune response against tumor cells, a fact that correlates with the poor response to immunotherapy. All these aspects will be addressed in this review, putting them in the context of the histological growth patterns of LM-CRC, a particular pathologic feature with both prognostic and predictive repercussions.
Highlights
Colorectal carcinoma (CRC) is the third most frequent tumor in the world and the second in Europe
In liver metastases from CRC (LM-CRC), curative surgery is the treatment of choice if it is performed in specialized centers
This means that the cancer-associated fibroblasts (CAFs) of a primary tumor may present different characteristics to the CAFs of a liver lesion [7,8] in the same patient, and therapies designed against colonic CAFs may not be efficient enough over hepatic CAFs
Summary
Colorectal carcinoma (CRC) is the third most frequent tumor in the world and the second in Europe. Despite the fact that many retrospective studies have identified poor prognostic factors such as tumor size or number of lesions [4], none of them provide enough information to take surgical decisions This fact highlights the need for new prognostic factors to select the best therapeutic approach for each patient. Even considering possible therapeutic strategies focused on stromal cells, we must bear in mind that fibroblasts demonstrate certain topographic differentiation [6] This means that the CAFs of a primary tumor may present different characteristics to the CAFs of a liver lesion [7,8] in the same patient, and therapies designed against colonic CAFs may not be efficient enough over hepatic CAFs. On the other hand, liver metastases have displayed a unique histologic feature, a histologic growth pattern (HGP) [9], that will be described in more detail (Figure 1). We will elucidate the relevance of the different cell types that shape up the liver microenvironment, the way in which they are structured, the altered immune response and the clinical and therapeutic consequences that can be derived from them
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