Differential clinical impacts of tumour budding evaluated by the use of immunohistochemical and haematoxylin and eosin staining in stage II colorectal cancer

Abstract

Aims The aim of this study was to clarify the quantitative and qualitative differences in tumour budding identification between haematoxylin and eosin (H&E) staining and immunohistochemical (IHC) staining for cytokeratin, and to estimate the respective clinical impacts in stage II colorectal cancer. Methods and results We retrospectively examined 314 surgically resected cases of stage II colorectal cancer, and assessed tumour budding on serial section slides with H&E staining and IHC staining for cytokeratin. Tumour budding counts based on cytokeratin‐stained slides were strongly correlated with those based on H&E‐stained slides, and had higher detection and reproducibility. On the basis of receiver operating characteristic analyses, the optimal cut‐off values of budding counts for relapse‐free survival (RFS) were 7 and 16 in a ×200 microscopic field with H&E and IHC staining, respectively. With these cut‐off values, tumour budding based on H&E staining had a significant correlation with RFS (80.3% and 93.2% of 5‐year RFS in the high‐budding group and the low‐budding group, respectively), and similar results were observed for IHC staining (79.9% and 91.7%, respectively). The Akaike Information Criterion value for RFS with H&E staining was favourable as compared with that with IHC staining. Conclusions Tumour budding counts based on cytokeratin‐stained slides showed higher detection and better reproducibility, but did not have as satisfactory clinical impacts as those based on H&E staining.

Immunohistochemical‑based molecular subtyping of colorectal carcinoma using maspin and markers of epithelial‑mesenchymal transition

“…For patients with stage II and III CRC, the nuclear expression of maspin has been demonstrated to predict sensitivity to 5-fluorouracil and levamisole (9,12,22). In addition to the findings of the present study, it can be postulated that patients with MSS-CRCs diagnosed with stage II or III, with high-grade budding and nuclear maspin predominance, involving mainly mesenchymal-type CRCs, may be responders in the case of adjuvant chemotherapy (21). On the other hand, patients with mesenchymal-type CRCs may benefit from anti-EMT-associated agents, which are currently being tested in clinical trials (4,23).…”

“…The present study demonstrated the potential prognostic value of tumor buds, high-grade budding indicating lower OS, decreased disease-free and relapse-free survival, and association with advanced tumor stages and the nuclear localization of maspin (6,8,10,20,21).…”

Interobserver Variability in the Assessment of Tumor Budding in pT 3/4 Colon Cancer: Improvement by Supporting Immunohistochemistry?

“…In conclusion, the results indicate that the general use of supporting cytokeratin staining is not superior to the ITBCC assessment criteria. Other studies comparing cytokeratin(only)-based assessments to H & E-based assessments demonstrated non superiority according to the prognostic value as well [12,13]. Small epithelial structures are straightforward to recognize on cytokeratin, but an elaborate study of experts has shown that the assessment of individual tumor buds using cytokeratin immunohistochemistry has just a moderate level of interobserver agreement, which indicates the issue with cytokeratin staining [14].…”

miR‑451 suppresses the malignant characteristics of colorectal cancer via targeting SAMD4B

“…Staining. The IHC assays were performed as described by Yamadera et al (30). In brief, the implanted xenograft tumor tissues were excised and fixed with 4% paraformaldehyde for 24 h at room temperature, dehydrated using a graded alcohol series of 60, 70, 80, 90, 95 and 100% ethanol and finally embedded in paraffin.…”