Histopathological growth patterns as a candidate biomarker for immunomodulatory therapy

Dam, Pieter-Jan van; Daelemans, Sofie; Ross, Elizabeth L.; Waumans, Yannick; Laere, Steven Van; Latacz, Emily; Steen, R. Van De; Pooter, Christel De; Kockx, Mark; Dirix, Luc; Vermeulen, Peter B.

doi:10.1016/j.semcancer.2018.01.009

Cited by 49 publications

(51 citation statements)

References 48 publications

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“…16 , who also demonstrated similar pNEN characteristics being associated with tumour grading and poor prognosis. Furthermore, similar histology-dependent variations in the immune profile have also been reported in several other cancers 17–21 . Our results seemed to similarly reflect an association between cancer differentiation and immune profile.…”

Section: Discussionsupporting

confidence: 78%

Profiling the Tumour Immune Microenvironment in Pancreatic Neuroendocrine Neoplasms with Multispectral Imaging Indicates Distinct Subpopulation Characteristics Concordant with WHO 2017 Classification

Takahashi

Kojima

Suzuki

et al. 2018

Sci Rep

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We successfully determined the difference of immune microenvironments between pNENs and pancreatic ductal adenocarcinomas (PDACs), and the histology-dependent variability among pNENs using multispectral fluorescent imaging system. Tumour tissue samples including 52 pNENs and 18 PDACs were investigated. The tumour-infiltrating lymphocytes (TILs), their PD-1 and PD-L1 expression in the pNENs were comprehensively and quantitatively analysed and were subsequently compared with those in PDACs. A principal component analysis revealed that the tissue immune profile is related to tumour histology, with distinct groups being observed for NETs, NECs, and PDACs. While NECs and some PDACs had hot immune microenvironments with abundant TILs, NETs had a cold immune microenvironment with few TILs. Moreover, in NETs, the numbers of intraepithelial PD-1high T cells and PD-L1high Type-II macrophages were elevated according to the grade. Univariate analysis revealed that lymph node metastasis, grade, stage, PD-1high T cells, and PD-L1high Type-II macrophages were predictors for recurrence-free survival (RFS), while grade and PD-1high T cells were prognostic factors for overall survival (OS). We also showed that PD-1high T cells and PD-L1high Type-II macrophages were associated with worse outcome in pNENs. Our results support the WHO 2017 tumour classification criteria, which distinguish between G3 NETs and NECs.

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Section: Discussionsupporting

confidence: 78%

Profiling the Tumour Immune Microenvironment in Pancreatic Neuroendocrine Neoplasms with Multispectral Imaging Indicates Distinct Subpopulation Characteristics Concordant with WHO 2017 Classification

Takahashi

Kojima

Suzuki

et al. 2018

Sci Rep

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“…Again, similar observations have been reported for angiotropic tumours [ 23 ]. Beyond the intrinsic changes in the tumour and stroma observed in replacement metastases, an effective immune response in patients with dHGP also might contribute to the difference in survival outcomes between these two HGPs [ 5 , 25 ]. Brunner et al demonstrated that capsule formation in dHGP strongly correlates with high levels of peri-tumour infiltration of CD4+, CD45RO+ and CD8+ cells [ 5 ].…”

Section: Discussionmentioning

confidence: 99%

Angiogenic desmoplastic histopathological growth pattern as a prognostic marker of good outcome in patients with colorectal liver metastases

et al. 2019

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Background In patients with resectable colorectal liver metastases (CRLM), distinct histopathological growth patterns (HGPs) develop at the interface between the tumour and surrounding tissue. The desmoplastic (d) HGP is characterised by angiogenesis and a peripheral fibrotic rim, whereas non-angiogenic HGPs co-opt endogenous sinusoidal hepatic vasculature. Evidence from previous studies has suggested that patients with dHGP in their CRLM have improved prognosis as compared to patients with non-desmoplastic HGPs. However, these studies were relatively small and applied arbitrary cut-off values for the determination of the predominant HGP. We have now investigated the prognostic effect of dHGP in a large cohort of patients with CRLM resected either with or without neoadjuvant chemotherapy. Methods All consecutive patients undergoing a first partial hepatectomy for CRLM between 2000 and 2015 at a tertiary referral centre were considered for inclusion. HGPs were assessed in archival H&E stained slides according to recently published international consensus guidelines. The dHGP was defined as desmoplastic growth being present in 100% of the interface between the tumour and surrounding liver. Results In total, HGPs in CRLMs from 732 patients were assessed. In the chemo-naive patient cohort ( n = 367), the dHGP was present in 19% ( n = 68) and the non-dHGP was present in 81% ( n = 299) of patients. This dHGP subgroup was independently associated with good overall survival (OS) (HR: 0.39, p < 0.001) and progression-free survival (PFS) (HR: 0.54, p = 0.001). All patients with any CRLM with a non-dHGP had significantly reduced OS compared to those patients with 100% dHGP, regardless of the proportion of non-dHGP (all p values ≤ 0.001). In the neoadjuvantly treated patient cohort ( n = 365), more patients were found to express dHGP ( n = 109, 30%) (adjusted odds ratio: 2.71, p < 0.001). On univariable analysis, dHGP was associated with better OS (HR 0.66, p = 0.009) and PFS (HR 0.67, p = 0.002). However, after correction for confounding by means of multivariable analysis no significant association of dHGP with OS (HR 0.92, p = 0.623) or PFS (HR 0.76, p = 0.065) was seen. Conclusions The current study demonstrates that the angiogenic dHGP in CRLM resected from chemo-naive patients acts as a strong, positive prognostic marker, unmatched by any other prognosticator. This observation warrants the evaluation of the clinical utility of HGPs in prospective clinical trials. Electronic supplementary material The online version of this article (10.1007/s1045...

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“…Post hoc analysis of the EORTC 40,983 trial demonstrated beneficial progression free survival in patients with elevated preoperative CEA levels (> 5 ng/ml) [15]. Furthermore, multiple previous studies have shown that the survival of patients with non-dHGP tumors is worse [11,12,16,17]. Also, non-dHGP (and especially the replacement-type of growth) is associated with several aggressive biological characteristics such as high histological grade, lack of inflammation, and increased cancer cell motility [11,12,16,17].…”

Section: Discussionmentioning

confidence: 99%

Histopathological growth patterns as biomarker for adjuvant systemic chemotherapy in patients with resected colorectal liver metastases

Buisman

Stok

Galjart

et al. 2020

Clin Exp Metastasis

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Adjuvant systemic chemotherapy (CTx) is widely administered in patients with colorectal liver metastases (CRLM). Histopathological growth patterns (HGPs) are an independent prognostic factor for survival after complete resection. This study evaluates whether HGPs can predict the effectiveness of adjuvant CTx in patients with resected CRLM. Two main types of HGPs can be distinguished; the desmoplastic type and the non-desmoplastic type. Uni- and multivariable analyses for overall survival (OS) and disease-free survival (DFS) were performed, in both patients treated with and without preoperative chemotherapy. A total of 1236 patients from two tertiary centers (Memorial Sloan Kettering Cancer Center, New York, USA; Erasmus MC Cancer Institute, Rotterdam, The Netherlands) were included (period 2000–2016). A total of 656 patients (53.1%) patients received preoperative chemotherapy. Adjuvant CTx was only associated with a superior OS in non-desmoplastic patients that had not been pretreated (adjusted hazard ratio (HR) 0.52, 95% confidence interval (CI) 0.37–0.73, p < 0.001), and not in desmoplastic patients (adjusted HR 1.78, 95% CI 0.75–4.21, p = 0.19). In pretreated patients no significant effect of adjuvant CTx was observed, neither in the desmoplastic group (adjusted HR 0.83, 95% CI 0.49–1.42, p = 0.50) nor in the non-desmoplastic group (adjusted HR 0.96, 95% CI 0.71–1.29, p = 0.79). Similar results were found for DFS, with a superior DFS in non-desmoplastic patients treated with adjuvant CTx (HR 0.71, 95% CI 0.55–0.93, p < 0.001) that were not pretreated. Adjuvant CTx seems to improve OS and DFS after resection of non-desmoplastic CRLM. However, this effect was only observed in patients that were not treated with chemotherapy.

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Histopathological growth patterns as a candidate biomarker for immunomodulatory therapy

Cited by 49 publications

References 48 publications

Profiling the Tumour Immune Microenvironment in Pancreatic Neuroendocrine Neoplasms with Multispectral Imaging Indicates Distinct Subpopulation Characteristics Concordant with WHO 2017 Classification

Profiling the Tumour Immune Microenvironment in Pancreatic Neuroendocrine Neoplasms with Multispectral Imaging Indicates Distinct Subpopulation Characteristics Concordant with WHO 2017 Classification

Angiogenic desmoplastic histopathological growth pattern as a prognostic marker of good outcome in patients with colorectal liver metastases

Histopathological growth patterns as biomarker for adjuvant systemic chemotherapy in patients with resected colorectal liver metastases

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