Tumor Budding Detection by Immunohistochemical Staining is Not Superior to Hematoxylin and Eosin Staining for Predicting Lymph Node Metastasis in pT1 Colorectal Cancer

Okamura, Takuma; Shimada, Yasuhiro; Nogami, Hitoshi; Kameyama, Hitoshi; Kobayashi, Takashi; Kosugi, Shin‐ichi; Wakai, Toshifumi; Ajioka, Yoichi

doi:10.1097/dcr.0000000000000567

Cited by 27 publications

(27 citation statements)

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“…The standard cut‐off values of budding counts (5 and 10 in a ×200 microscopic field) have been determined on H&E‐stained slides . Conversely, the method for evaluation of budding counts based on IHC staining has been controversial . The cut‐off values were arbitrarily determined in some studies, whereas some studies have proposed cut‐off values of 8, 16 and 25 for stage I, I/II and I/II/III CRC, respectively, on the basis of ROC analyses .…”

Section: Discussionmentioning

confidence: 99%

“…1,3,26 Conversely, the method for evaluation of budding counts based on IHC staining has been controversial. 7,8,[28][29][30] The cutoff values were arbitrarily determined in some studies, whereas some studies have proposed cut-off values of 8, 16 and 25 for stage I, I/II and I/II/III CRC, respectively, on the basis of ROC analyses. 7,8,28 These data indicate that appropriate cut-off values depend on cancer stages and staining procedures; therefore, we considered that study methodology-specific cut-off values determined by the use of ROC curves were required.…”

Section: Discussionmentioning

confidence: 99%

“…Tumour budding has generally been evaluated by haematoxylin and eosin (H&E) staining, but does not always show favourable reproducibility. Recent reports have suggested that immunohistochemical (IHC) staining for cytokeratin has the potential to improve the objective diagnosis of tumour budding over detection based on H&E staining, because cytokeratin is a component of the cancer cell cytoskeletons, and IHC staining for cytokeratin highlights cancer cells in the stroma . Okamura et al .…”

Section: Introductionmentioning

confidence: 99%

“…Recent reports have suggested that immunohistochemical (IHC) staining for cytokeratin has the potential to improve the objective diagnosis of tumour budding over detection based on H&E staining, because cytokeratin is a component of the cancer cell cytoskeletons, and IHC staining for cytokeratin highlights cancer cells in the stroma. [7][8][9] Okamura et al 8 reported that the j values describing interobserver agreement on tumour budding were 0.44 and 0.66 for H&E and cytokeratin staining respectively. However, tumour budding detected with IHC staining was inferior to that detected with H&E staining in terms of predicting lymph node metastasis in pT1 CRC.…”

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

et al. 2019

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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confidence: 99%

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

et al. 2019

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“…However, Okamura et al claimed that keratin immunohistochemistry was not superior to HE for predicting lymph node metastasis in early colorectal cancer [36]. The optimal method for the evaluation of tumor budding, including the superiority of keratin immunohistochemistry to HE, in early oral tongue carcinoma should be explored in future studies.…”

Section: Discussionmentioning

confidence: 99%

Predictive Significance of Tumor Depth and Budding for Late Lymph Node Metastases in Patients with Clinical N0 Early Oral Tongue Carcinoma

Hori

Kubota

Yokose

et al. 2017

Head and Neck Pathol

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Construction and validation of artificial intelligence pathomics models for predicting pathological staging in colorectal cancer: Using multimodal data and clinical variables

Tan,

Liu,

Xue

et al. 2024

Cancer Medicine

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ObjectiveThis retrospective observational study aims to develop and validate artificial intelligence (AI) pathomics models based on pathological Hematoxylin–Eosin (HE) slides and pathological immunohistochemistry (Ki67) slides for predicting the pathological staging of colorectal cancer. The goal is to enable AI‐assisted accurate pathological staging, supporting healthcare professionals in making efficient and precise staging assessments.MethodsThis study included a total of 267 colorectal cancer patients (training cohort: n = 213; testing cohort: n = 54). Logistic regression algorithms were used to construct the models. The HE image features were used to build the HE model, the Ki67 image features were used for the Ki67 model, and the combined model included features from both the HE and Ki67 images, as well as tumor markers (CEA, CA724, CA125, and CA242). The predictive results of the HE model, Ki67 model, and tumor markers were visualized through a nomogram. The models were evaluated using ROC curve analysis, and their clinical value was estimated using decision curve analysis (DCA).ResultsA total of 260 deep learning features were extracted from HE or Ki67 images. The AUC for the HE model and Ki67 model in the training cohort was 0.885 and 0.890, and in the testing cohort, it was 0.703 and 0.767, respectively. The combined model and nomogram in the training cohort had AUC values of 0.907 and 0.926, and in the testing cohort, they had AUC values of 0.814 and 0.817. In clinical DCA, the net benefit of the Ki67 model was superior to the HE model. The combined model and nomogram showed significantly higher net benefits compared to the individual HE model or Ki67 model.ConclusionThe combined model and nomogram, which integrate pathomics multi‐modal data and clinical‐pathological variables, demonstrated superior performance in distinguishing between Stage I–II and Stage III colorectal cancer. This provides valuable support for clinical decision‐making and may improve treatment strategies and patient prognosis. Furthermore, the use of immunohistochemistry (Ki67) slides for pathomics modeling outperformed HE slide, offering new insights for future pathomics research.

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Tumor Budding Detection by Immunohistochemical Staining is Not Superior to Hematoxylin and Eosin Staining for Predicting Lymph Node Metastasis in pT1 Colorectal Cancer

Abstract: Tumor budding detected by CAM5.2 staining was not superior to hematoxylin and eosin staining for predicting lymph node metastasis in pT1 colorectal cancer.

Cited by 27 publications

References 31 publications

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

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

Predictive Significance of Tumor Depth and Budding for Late Lymph Node Metastases in Patients with Clinical N0 Early Oral Tongue Carcinoma

Construction and validation of artificial intelligence pathomics models for predicting pathological staging in colorectal cancer: Using multimodal data and clinical variables

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