Tumour budding with and without admixed inflammation: two different sides of the same coin?

Abstract

Background:Tumour budding is an adverse prognostic indicator in colorectal cancer (CRC). Marked overall peritumoural inflammation has been associated with favourable outcome and may lead to the presence of isolated cancer cells due to destruction of invading cancer cell islets.Methods:We assessed the prognostic significance of tumour budding and peritumoural inflammation in a cohort of 381 patients with CRC applying univariate and multivariate analyses.Results:Patients with high-grade budding and marked inflammation had a significantly better outcome compared with patients with high-grade budding and only mild inflammation. Outcome in these cases, however, was still worse compared with cases with low-grade budding, in which the extent of peritumoural inflammation had no further prognostic effect.Conclusions:Tumour budding proved to be a powerful prognostic variable in patients with CRC. Scattering of invading cancer cell islets by marked overall peritumoural inflammation seems to have a minor role.

A novel prognostic model for tongue squamous cell carcinoma based on the characteristics of tumour and its microenvironment: iBD score

“…It has been reported that tumour budding was associated with parameters of TME and was an independent adverse prognostic factor in CRC and breast cancer . Max et al . combined analysis of tumour budding and inflammatory cell reaction in CRC and found that the inflammation element could stratify cases with high‐grade budding into two distinct prognostic groups, but had a minor role in cases with low‐grade budding.…”

“…It has been reported that tumour budding was associated with parameters of TME and was an independent adverse prognostic factor in CRC 28 and breast cancer. 30 Max et al 31 combined analysis of tumour budding and inflammatory cell reaction in CRC and found that the inflammation element could stratify cases with high-grade budding into two distinct prognostic groups, but had a minor role in cases with low-grade budding. Earlier reports in breast cancer have shown that there was a weaker peritumoural inflammatory infiltrate, as measured by KM grade in patients with high-grade tumour budding, and an association between tumour budding and increased amount of TSP.…”

Tumor Budding: The Name is EMT. Partial EMT.

“…However, there are certain situations when it is particularly difficult to decide, in routine H&E staining, whether a bud-looking structure is actually a bud. These situations include: (i) abundant inflammatory infiltrate at the invasive front, which makes it hard to distinguish between real buds and activated lymphocytes and histiocytes; (ii) abundant stromal reaction at the invasive front, which makes it hard to distinguish between real buds and stromal cells; (iii) fragmentation of tumor glands induced by abundant inflammatory infiltrate, which gives them a bud-looking appearance (in fact tumor budding is inversely correlated with the intensity of inflammation [ 32 ]); (iv) retraction artifacts around fragmented tumor glands, which gives them a bud-looking appearance; and (v) fragments of tumor tissue surrounded by an abundant mucinous extracellular matrix, which gives them a bud-looking appearance. For (i) and (ii), where H&E staining cannot easily distinguish between real buds and other structures, a cytokeratin immunostaining should be used.…”

“…, the intensity of tumor budding, which best separates them into prognostic categories, followed by appropriate therapeutic decisions. Many reports tended to favor the cutoff = 10 buds [ 16 , 19 , 20 , 25 , 32 , 36 ], with some reports having relied on either the Kaplan-Meier plots themselves [ 20 ] or receiver operating characteristic curves with survival as the endpoint, which were constructed based on a subset of the patients and run for calibration [ 36 ]. Other studies, however, chose this value arbitrarily or based on previous publications [ 16 , 19 , 25 ].…”

Validation of the International Tumor Budding Consensus Conference 2016 recommendations on tumor budding in stage I-IV colorectal cancer

“…Key aspects of this proposal (hot-spot, 20x magnification and 0,785 mm2) were adopted by the Japanese Society for Cancer of the Colon and the Rectum (JSCCR) prior to the ITBCC, and routine reporting of tumor budding in pT1 tumors according to this method has been performed since 2009 [21] . Indeed, this system has been used in studies including large Japanese patient cohorts with pT1 CRC [11,22] and by others with slight variations, such as an adapted HPF size of 0.95mm 2 [23][24][25]. However, a standardized consensus approach such as provided by the ITBCC guidelines is essential for tumor budding to be validated, to compare study results and ultimately be used as a biomarker in routine diagnostics.…”