Biological and Prognostic Significance of the Morphological Types and Vascular Patterns in Colorectal Liver Metastases (CRLM)

Abstract

Patients with encapsulated colorectal liver metastases (CRLM) have a better prognosis than those without a capsule. The reason for the encapsulation is unknown. Hypoxia inducible factor-1α (HIF-1α) increases tumor angiogenesis and tumor tissue expression is associated with reduced survival. Our aim was to determine whether the good prognosis of encapsulated CRLM is associated with reduced HIF-1α expression by the cancer.The study selected only patients who had not undergone neoadjuvant chemotherapy prior to a potentially curative hepatectomy for CRLM. From 30 selected patients, serial sections were cut from a single randomly selected metastasis. Morphology was assessed following H&E staining. Tumor hypoxia, vascular endothelial growth factor (VEGF), proliferation, and microvascular density (MVD) were assessed by immunostaining for HIF-1α and carbonic anhydrase-9 (CA-9), VEGF, Ki67, and cluster of differentiation-31, respectively. MVD was calculated in the vascular hot spots. Pathology was reported without clinical outcome information. Actual long-term survival was recorded.Thirteen (43%) of the cancers were encapsulated CRLM containing glands which were large, complex, and cribriform. Thirteen (43%) were infiltrative CRLM and their glands were small, closely packed, and rounded with vessels in the interglandular fibrous tissue with no capsule; 3 (10%) had a mixed picture. Encapsulated CRLM had a higher expression of HIF-1α (58% vs 8%, P = 0.03), CA-9 (42% vs 0%, P = 0.04), and VEGF (92% vs 25%, P = 0.02). MVD was lower in the encapsulated CRLM group (37 mm2 vs 143 mm2, P < 0.001). The median follow-up was 115 months. The encapsulated CRLM group had a better overall and 5-year survival (relative hazard: 0.58, P = 0.057 and hazard ratio: 0.52, P = 0.044).There are 2 main morphological appearances of CRLM which have very different long-term survival following liver resection surgery. The morphology is associated with differences in expression of HIF-1α, CA-9, VEGF, and angiogenesis.

Growth patterns of colorectal cancer liver metastases and their impact on prognosis: a systematic review

“…We found that in addition to the four studies in which the desmoplastic pattern was a separate parameter, a ‘mixed’ pattern was reported independently of the three main patterns in a further three studies, 14 15 44 and independently of the desmoplastic and replacement patterns in a fourth. 28 Frequencies for a mixed pattern were 18.6% 15 and 17.6% 14 in two larger cohorts and 10% 28 and 41.4% 44 in two smaller ones. Intralesional heterogeneity was also reflected indirectly in some studies that did not quantify this feature, stating that heterogeneity was ‘uncommon’, 31 or that ‘usually’ or ‘in most of the cases’, only one growth pattern was present.…”

Pathological factors and prognosis of resected liver metastases of colorectal carcinoma: implications and proposal for a pathological reporting protocol

“…reported that patients with a thick fibrous pseudocapsule (number of collagen bundles ≥10) had better 5‐year survival than patients with a thin fibrous pseudocapsule (number of collagen bundles <10) or no fibrous pseudocapsule (88% versus 64% and 31%, respectively, P < 0.001). Other studies have reported comparable results, noting that the absence of a tumour pseudocapsule was associated with worse survival and higher recurrence . Only one study has failed to demonstrate the prognostic significance of a tumour pseudocapsule .…”

“…Other studies have reported comparable results, noting that the absence of a tumour pseudocapsule was associated with worse survival and higher recurrence. 63,75,[81][82][83][84][85] Only one study has failed to demonstrate the prognostic significance of a tumour pseudocapsule. 38 Recently, Fernand ez-Aceñero et al 70 reported an association between regression grade and the presence of a pseudocapsule after neoadjuvant chemotherapy (P = 0.009).…”

Differential regulation of extracellular matrix proteins in three recurrent liver metastases of a single patient with colorectal cancer

“…TGFI inhibits the transforming growth factor β (TGF-β) signaling pathway, which plays a crucial role in fibrotic events as reported previously [ 28 ]. In line with the poor prognosis and lower overall survival rates reported for non-encapsulated CRLM [ 29 ], the upregulation of TGFI may be a hint towards a higher malignancy of the third and also last CRLM of the patient before he succumbed to the disease. Furthermore, in M3 in contrast to M1 and M2, we also observed a downregulation of laminin subunit beta-2 (LAMB2), decorin (DCN) and coagulation factor XIII A chain (F13A1), which are said to be associated with good prognosis in CRC (Fig.…”