Histopathological Growth Pattern, Proteolysis and Angiogenesis in Chemonaive Patients Resected for Multiple Colorectal Liver Metastases

Abstract

The purpose of this study was to characterise growth patterns, proteolysis, and angiogenesis in colorectal liver metastases from chemonaive patients with multiple liver metastases. Twenty-four patients were included in the study, resected for a median of 2.6 metastases. The growth pattern distribution was 25.8% desmoplastic, 33.9% pushing, and 21% replacement. In 20 patients, identical growth patterns were detected in all metastases, but in 8 of these patients, a second growth pattern was also present in one or two of the metastases. In the remaining 4 patients, no general growth pattern was observed, although none of the liver metastases included more than two growth patterns. Overall, a mixed growth pattern was demonstrated in 19.3% of the liver metastases. Compared to metastases with pushing, those with desmoplastic growth pattern had a significantly up-regulated expression of urokinase-type plasminogen activator receptor (P = 0.0008). Angiogenesis was most pronounced in metastases with a pushing growth pattern in comparison to those with desmoplastic (P = 0.0007) and replacement growth pattern (P = 0.021). Although a minor fraction of the patients harboured metastases with different growth patterns, we observed a tendency toward growth pattern uniformity in the liver metastases arising in the same patient. The result suggests that the growth pattern of liver metastases is not a random phenomenon.

The morphological growth patterns of colorectal liver metastases are prognostic for overall survival

“…[1][2][3][4] The desmoplastic growth pattern is consistent with high proteolytic activity. 4,5 Although the morphological categorization described by Vermeulen et al 3 has been recognized in various studies, the prognostic significance remains controversial. Van den Eynden et al 3 identified pushing growth as an independent predictor of poor 2-year survival, whereas Nagashima et al 6 found a detrimental effect of an infiltrative tumor margin similar to the replacement pattern.…”

“…Metastases with mixed-type margins have been reported earlier, but guidelines for cut-off point and categorization have not yet been published. [1][2][3][4] In previous studies, little intra-and inter-observer variability was found for Vermeulen's procedure. 1,2,4 After consensus readings by two observers (KN and BV) of 20 cases, one observer (KN) assessed all sections.…”

The Multifaceted Role of the Microenvironment in Liver Metastasis: Biology and Clinical Implications

“…Different histologic patterns in the tumor-liver interface of solid tumors were described by Terayama and colleagues (94) and Vermeulen and colleagues (95), based on microscopic examination of hematoxylin and eosin and Gordon Sweet's silver (reticulin) staining. This assessment is reproducible (95,96). Figure 2 summarizes the characteristics of each of the growth patterns.…”

“…Namely, in patients with multiple liver metastases, one growth pattern generally predominates (95,96,98). Furthermore, the growth patterns depend on the tissue of origin of the primary tumor (94,95,99).…”

“…Furthermore, the growth patterns depend on the tissue of origin of the primary tumor (94,95,99). In liver metastases of CRC, all 3 growth patterns are observed at different proportions, depending on the study population (95)(96)(97). On the other hand, liver metastases of breast cancer have a preponderance of replacement growth pattern (98), and this growth pattern is also prevalent in liver metastases of other adenocarcinoma histiotypes such as pancreatic and urothelial carcinoma (Vermeulen et al, unpublished observation; discussed in ref.…”