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

Abstract

Colorectal metastases in the liver grow according to three histological patterns: a pushing pattern, a replacement pattern, and a desmoplastic pattern. The objective of the current study was to explore the prognostic significance of these three growth patterns for survival. The study included 217 consecutive patients, liver resected between 2007 and 2011 due to hepatic metastases from colorectal adenocarcinoma. The growth patterns were assessed on archival hematoxylin and eosin-stained tissue sections. In 150 metastases, the density of the immune cell infiltrate at the tumor periphery was judged by a semi-quantitative method. The prevalence of the pushing-type, the desmoplastic-type, and the replacement-type was 33%, 32%, and 11%, respectively; 24% of the metastases displayed a mixed pattern. Kaplan-Meier analysis and Cox regression demonstrated a prognostic significance of the growth patterns (P ¼ 0.0006, log-rank test), as the replacement pattern appeared as an independent predictor of poor overall survival. For patients with replacement growth, the hazard of death was 2-2.5 times higher than for patients with pushing growth (P ¼ 0.004, cox regression) or mixed growth (P ¼ 0.01), and nearly four times higher than for patients with desmoplastic growth (Po0.0001). The negative prognostic effect of the replacement growth pattern was even more pronounced after adjusting for tumor size. Desmoplastic growth corresponded with small tumor size, dense lymphocytic infiltration and a more favorable prognosis. Eventually, the growth patterns may contribute to a histology-based prognostic biomarker for patients with colorectal liver metastases. Modern Pathology (2014) 27, 1641-1648; doi:10.1038/modpathol.2014.4; published online 23 May 2014Keywords: colorectal cancer; growth pattern; histopathology; liver; metastasis; prognosis; survival During the last 5-10 years, major advances have been made in both the medical and surgical treatment of liver metastases from colorectal carcinoma. The number of patients who undergo liver resection with curative intent has therefore increased significantly. However, so far, little is known on the biological, clinical, and histopathological features that determine prognosis after hepatic resection. The revised and more active treatment strategy has thus fostered a demand for new and better prognostic and predictive markers that can be used for selecting the right treatment regimen for each patient. For primary colorectal cancer, the malignant transformation from adenoma to carcinoma is by now very well described; far less described are the events that govern the progression of metastases in the liver. A greater understanding of the diverse infiltration mechanisms of the metastases, including the intricate interaction with the hepatic microenvironment, might lead to new prognostic and therapeutic prospects.Vermeulen et al 1 identified three histological growth patterns for colorectal liver metastases, suggesting biological differences: (i) a pushing growth pattern, in which the metastasis e...

Resection Margin and Survival in 2368 Patients Undergoing Hepatic Resection for Metastatic Colorectal Cancer

“…Brunner et al 21 revealed that a compact growth pattern (confined by a capsule) was associated with both higher R0 rate and improved survival. A similar observation was noted by Nielsen et al 8 who identified an infiltrative growth pattern as an independent predictor of poor survival, whereas favorable prognosis was correlated with a desmoplastic growth pattern, in which a fibrous rim separates the metastasis from the liver parenchyma. It is noteworthy that both studies 8,21 reported that the compact growth pattern (confined by a capsule) was associated with an increased lymphocytic infiltrate at the tumor margin , which is a recognized favorable prognostic factor in colorectal cancer.…”

“…A similar observation was noted by Nielsen et al 8 who identified an infiltrative growth pattern as an independent predictor of poor survival, whereas favorable prognosis was correlated with a desmoplastic growth pattern, in which a fibrous rim separates the metastasis from the liver parenchyma. It is noteworthy that both studies 8,21 reported that the compact growth pattern (confined by a capsule) was associated with an increased lymphocytic infiltrate at the tumor margin , which is a recognized favorable prognostic factor in colorectal cancer. 22–25 Thus, a confounding effect can be attributed to the capsule subtype of tumor growth pattern, which was proposed as a mechanical and chemical barrier to local invasion by tumor cells.…”

“…This definition may be influenced by the tumor growth pattern as it has been demonstrated that growth pattern correlates with both R1 resection rate and survival 8 . Furthermore, it has been reported that 95% and 70% of microsatellite lesions, when present, are located within 1cm and 2mm from the tumor margin, respectively.…”

Inflammation and uPAR-Expression in Colorectal Liver Metastases in Relation to Growth Pattern and Neo-adjuvant Therapy

“…A mix of two or three GPs is categorised as mixed GP. Patients resected for liver metastases with a desmoplastic GP have a superior survival in comparison to patients resected for liver metastases with a pushing, replacement or mixed growth pattern [18,19]. The aim of this study was to investigate the correlation between GP and specific immune-relevant markers in the immediate tumour surroundings, specifically by evaluating the infiltration of macrophages and T cells and the urokinase-type plasminogen activation receptor (uPAR).…”

Positive Margins After Resection of Metastatic Colorectal Cancer in the Liver: Back to the Drawing Board?

“…Recent data has supported that idea that growth patterns are probably relevant and may explain the link between margins and outcome. 4,5 The debate has certainly not been laid to rest.…”