Clinical implications and mechanism of histopathological growth pattern in colorectal cancer liver metastases

Table 1 Studies on stratification value of histopathological growth pattern in colorectal cancer liver metastasis

Year	Factors	Prediction	Distribution of HGPs	Ref.
Survival stratification
2018-2019	dHGP and rHGP (based on radiomics)	dHGP vs rHGP and mixed HGP: longer PFS (no detail)	119 patients: dHGP (206 lesions), rHGP (140 lesions)	Wei et al[43]
2004-2019	Pushing GP and infiltrative GP	Infiltrative GP vs pushing GP: Worse OS (50.2 mo vs 92 mo) and DFS (10.5 mo vs 21.5 mo), higher intrahepatic recurrence (75% vs 20%)	266 patients: Infiltrative (n = 182, 68.4%) and pushing (n = 84, 31.6%)	Jayme et al[16]
2005-2017	dHGP and non-dHGP group; metabolic-clinical risk score	dHGP vs non-dHGP: Longer 5 yr OS (83.3% vs 34.3%) and 10 yr OS (62.5% vs 22.8%) and DFS (14.4 mo vs 8.3 mo)	108 patients: dHGP (26, 20%), non-dHGP (38, 35%)	Bohlok et al[23]
2000-2015	dHGP and non-dHGP; positive resection margins (R1) and negative resection margins(R0)	Non-dHGP vs dHGP: worse OS (50 mo vs 80 mo), higher risk of positive resection margins (76.6% vs 23.4%)	1302 patients: dHGP (305, 23%) and non-dHGP (997, 77%); R1 (170, 13%) and R0 (1132, 87%)	Nierop et al[9]
2004-2017	dHGP and non-dHGP, clinical risk score, the immunoscore	dHGP vs non-dHGP: Higher immunoscore (51.9% vs 33%), longer relapse free survival (32 mo vs 12 mo) and OS (not reached vs 40 mo)	166 patients: dHGP (54, 32.5%), non-dHGP (112, 67.5%)	Liang et al[4]
2012-2017	Expanding GP, infiltrating GP; low tumor budding score, and Crohn's disease-like response	Expanding GP in primary CRC: dHGP liver metastasis and better OS (no detail); infiltrating GP in primary carcinoma: rHGP liver metastasis and worse OS (no detail)	29 patients; primary CRC: expanding GP (11, 37.9%) and infiltrating GP (18, 62.1%); liver metastasis: dHGP (15, 51.7%) and rHGP (14, 48.2%)	Wu et al[19]
2000-2015	dHGP and non-dHGP	dHGP vs non-dHGP: More liver-limited disease recurrence (43% vs 31%); less frequently experience multi-organ recurrence (19% vs 34%)	690 patients: dHGP (173, 25%) and non-dHGP (517, 75%)	Nierop et al[17]
2000-2009	Infiltrative and pushing tumor margin	Infiltrative margin vs pushing margin: poorer 5 yr DFS (20.2% vs 40.5%)	91 patients: infiltrative margin (54, 59.3%) and pushing margin (37, 40.7%)	Pinheiro et al[12]
2007-2011	dHGP, rHGP, pHGP, mixed HGP	rHGP vs dHGP, pHGP and mixed HGP: Poorer OS (22.8 mo vs > 60 mo, 44.2 mo and 40.3 mo)	217 patients: pHGP(33%), dHGP(32%), rHGP(11%) and mixed HGP(24%)	Nielsen et al[8]
1997-2005	dHGP, rHGP, pHGP, mixed HGP	pHGP vs dHGP, rHGP and mixed HGP: Poorer 2 yr OS (43.8% vs 72.5%, 70.2%, and 54.3%)	205 patients: pHGP (15.6%), dHGP (34.6%), rHGP (27.8%) and mixed HGP (17.6 %)	Van den Eynden et al[13]
Therapy response stratification
2000-2016	dHGP and non-dHGP	Non-dHGP: Superior response to adjuvant systemic chemotherapy on improving OS and DFS but only in patients that were not treated with chemotherapy	1236 patients; 580 not pretreated patients (46.9%): dHGP (91, 15.6%) and non-dHGP (489, 84.4%); 656 pretreated patients (53.1%), dHGP (189, 28.8%) and non-dHGP (467, 71.2%).	Buisman et al[27]
2000-2015	dHGP and non-dHGP	dHGP vs non-dHGP: Better 5-year PFS (50% vs 19%) and 5 yr OS (70% vs 37%) but only in chemo-naive patients with resecting CRCLM	732 patients; in the chemo-naive patient cohort (n = 367), dHGP (68, 19%) and non-dHGP (299, 81%); in the neoadjuvantly treated patient cohort (n = 365), dHGP (109, 30%) and non-dHGP (256, 70%)	Galjart et al[6]
2010-2013	dHGP, rHGP, pHGP, mixed HGP	pHGP: Worse OS and DFS; significantly associated with Oxaliplatin-based chemotherapy	110 patients: pHGP (33, 30%), dHGP (23, 21%), rHGP (19, 18%) and mixed HGP (34, 31%)	Falcao et al[11]

HGP: Histopathological growth pattern; GP: Growth pattern; dHGP: Desmoplastic histopathological growth pattern; rHGP: Replacement histopathological growth pattern; pHGP: Pushing histopathological growth pattern; OS: Overall survival; DFS: Disease-free survival; PFS: Progression-free survival.

Table 2 Characteristics of desmoplastic histopathological growth pattern and replacement histopathological growth pattern in colorectal cancer liver metastasis

Aspects	dHGP	rHGP
Morphology	Sharp desmoplastic rim separating tumor cells from adjacent liver	Ill-defined border; Tumor cells replace normal hepatocytes along with the architecture of liver plate
Invasion pattern	Expanding and mild	Infiltrative and aggressive
Immune phenotype	Abundant	Desert
Vascularization	Angiogenesis	Non-angiogenesis (vessel co-option)
Organ-specific	No, widely appears in brain, lung and liver	Yes, only appears in liver
Therapy response	Superior response	Inferior response and drug resistance
Clinical outcome	Longer OS, DFS and PFS	Poorer survival and high recurrence

dHGP: Desmoplastic histopathological growth pattern; rHGP: Replacement histopathological growth pattern; OS: Overall survival; DFS: Disease-free survival; PFS: Progression-free survival.