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

Martin, Benedikt; Mayr, N. Patrick; Ihringer, Regina; Schäfer, Eva-Maria; Jakubowicz, Elżbieta; Anthuber, Matthias; Schenkirsch, Gerhard; Schaller, Tina; Märkl, Bruno

doi:10.3390/diagnostics10090730

Cited by 4 publications

(2 citation statements)

References 18 publications

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“…Investigations of the tumor border configuration (as defined by Jass) indicated suboptimal interobserver agreement [ 6 ]. Tumor budding might also have considerable interobserver variability [ 15 , 29 , 42 , 43 ]. However, the tumor–stroma ratio indicated a similarly low interobserver variability as SARIFA, and the assessment was also relatively simple and quick (<2 min) [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Stroma AReactive Invasion Front Areas (SARIFA)—A New Easily to Determine Biomarker in Colon Cancer—Results of a Retrospective Study

Martin

Grosser

Kempkens

et al. 2021

Cancers

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Many studies have used histomorphological features to more precisely predict the prognosis of patients with colon cancer, focusing on tumor budding, poorly differentiated clusters, and the tumor–stroma ratio. Here, we introduce SARIFA: Stroma AReactive Invasion Front Area(s). We defined SARIFA as the direct contact between a tumor gland/tumor cell cluster (≥5 cells) and inconspicuous surrounding adipose tissue in the invasion front. In this retrospective, single-center study, we classified 449 adipose-infiltrative adenocarcinomas (not otherwise specified) from two groups based on SARIFA and found 25% of all tumors to be SARIFA-positive. Kappa values between the two pathologists were good/very good: 0.77 and 0.87. Patients with SARIFA-positive tumors had a significantly shorter colon-cancer-specific survival (p = 0.008, group A), absence of metastasis, and overall survival (p < 0.001, p = 0.003, group B). SARIFA was significantly associated with adverse features such as pT4 stage, lymph node metastasis, tumor budding, and higher tumor grade. Moreover, SARIFA was confirmed as an independent prognostic indicator for colon-cancer-specific survival (p = 0.011, group A). SARIFA assessment was very quick (<1 min). Because of low interobserver variability and good prognostic significance, SARIFA seems to be a promising histomorphological prognostic indicator in adipose-infiltrative adenocarcinomas of the colon. Further studies should validate our results and also determine whether SARIFA is a universal prognostic indicator in solid cancers.

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Section: Discussionmentioning

confidence: 99%

Stroma AReactive Invasion Front Areas (SARIFA)—A New Easily to Determine Biomarker in Colon Cancer—Results of a Retrospective Study

Martin

Grosser

Kempkens

et al. 2021

Cancers

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“…For histological evaluation, H&E staining was done to observe the colonic histology differences by the method of Martin B [27]. Moreover, the H&E results were observed 1.…”

Section: Morphological and Histological Evaluationmentioning

confidence: 99%

Analysis of Colorectal Carcinogenesis Paradigm between Cold Constitution and Heat Constitution: Earlier ECM Collagen Deposition

Nong

Liang

Xing

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Colorectal cancer (CRC) is a common malignant tumor around the world. Studying the unique constitution of CRC patients is conducive to the application of personalized medical treatment for CRC. The most common types of constitution in CRC are cold and heat constitution. A previous study has suggested that the malignant progression in cold and heat constitution CRC are different; however, the mechanism remains unclear. The tumor microenvironment (TME) is likely to vary with each individual constitution, which may affect the tumor growth in different constitutions. The extracellular matrix (ECM), the most important component of TME, plays a critical role in disease progression and outcome in patients with CRC. Moreover, collagen, the major component of the ECM, determines the main functional characteristics of ECM and tissue fibrosis caused by collagen deposition, which is one of the signs of CRC malignant progression. This study aimed to explore the mechanisms leading to different colorectal carcinogenesis paradigms between the cold constitution and heat constitution within the context of ECM collagen deposition. We established the CRC rat models and enrolled 30 CRC patients with cold and heat constitution. The collagen-related parameters were detected by using Sirius red staining combined with polarized light microscope, and expressions of collagen (COL I and COL III) and lysyl oxidase (LOX and LOXL2) were determined using immunohistochemistry, while the mRNA levels of COL1A1, COL3A1, LOX, and LOXL2 were measured by qRT-PCR. We found that a higher degree of collagen deposition in the cold-constitution group. The results suggest cold and heat constitution may affect the colorectal carcinogenesis paradigm by influencing the early collagen deposition in colon tissue. The study may provide an effective idea for clinicians to improve the prognosis of CRC patients with different constitutions.

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Immunohistochemical analysis of tumor budding in stage II colon cancer: exploring zero budding as a prognostic marker

Pihlmann Kristensen,

Korsgaard,

Timm

et al. 2024

Virchows Arch

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Tumor budding, a biomarker traditionally evaluated using hematoxylin and eosin (H&E) staining, has gained recognition as a prognostic biomarker for stage II colon cancer. Nevertheless, while H&E staining offers valuable insights, its limitations prompt the utilization of pan-cytokeratin immunohistochemistry (IHC). Consequently, this study seeks to evaluate the prognostic significance of tumor budding using IHC in a contemporary cohort of stage II colon cancer patients, aiming to deepen our understanding of this critical facet in cancer prognosis. We conducted a retrospective, population-based cohort study including 493 patients with stage II colon cancer and evaluated tumor budding using IHC, following the H&E-based guidelines proposed by the International Tumor Budding Consensus Conference Group. Correlation between H&E-based and IHC-based tumor budding was assessed using a four-tiered scoring system that included a zero budding (Bd0) category. Survival analyses explored the prognostic significance of tumor budding assessed by IHC and H&E. As expected, IHC-based tumor budding evaluation yielded significantly higher bud counts compared to H&E (p < 0.01). Interestingly, 21 patients were identified with no tumor budding using IHC. This was associated with significantly improved recurrence-free survival (HR = 5.19, p = 0.02) and overall survival (HR = 4.47, p = 0.04) in a multivariate analysis when compared to tumors with budding. The Bd0 category demonstrated a 100% predictive value for the absence of recurrence. In conclusion, IHC-based tumor budding evaluation in stage II colon cancer provides additional prognostic information. The absence of tumor budding is associated with a favorable prognosis and may serve as a potential marker for identifying patients with no risk of recurrence.

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

Cited by 4 publications

References 18 publications

Stroma AReactive Invasion Front Areas (SARIFA)—A New Easily to Determine Biomarker in Colon Cancer—Results of a Retrospective Study

Stroma AReactive Invasion Front Areas (SARIFA)—A New Easily to Determine Biomarker in Colon Cancer—Results of a Retrospective Study

Analysis of Colorectal Carcinogenesis Paradigm between Cold Constitution and Heat Constitution: Earlier ECM Collagen Deposition

Immunohistochemical analysis of tumor budding in stage II colon cancer: exploring zero budding as a prognostic marker

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