Tumor Budding Is an Independent Adverse Prognostic Factor in Pancreatic Ductal Adenocarcinoma

Abstract

Tumor budding is a well-established adverse prognostic factor in colorectal cancer. However, the significance and diagnostic reproducibility of budding in pancreatic carcinoma requires further study. We aimed to assess the prognostic significance of tumor budding in pancreatic ductal adenocarcinoma, determine its relationship with other clinicopathologic features, and assess interobserver variability in its diagnosis. Tumor budding was assessed in 192 archival cases of pancreatic ductal adenocarcinoma using hematoxylin and eosin (H&E) sections; tumor buds were defined as single cells or nonglandular clusters composed of <5 cells. The presence of budding was determined through assessment of all tumor-containing slides, and associations with clinicopathologic features and outcomes were analyzed. Six gastrointestinal pathologists participated in an interobserver variability study of 120 images of consecutive tumor slides stained with H&E and cytokeratin. Budding was present in 168 of 192 cases and was associated with decreased overall survival (P=0.001). On multivariable analysis, tumor budding was prognostically significantly independent of stage, grade, tumor size, nodal status, lymphovascular invasion, and perineural invasion. There was substantial agreement among pathologists in assessing the presence of tumor budding using both H&E (K=0.63) and cytokeratin (K=0.63) stains. The presence of tumor budding is an independent adverse prognostic factor in pancreatic ductal carcinoma. The assessment of budding with H&E is reliable and could be used to better risk stratify patients with pancreatic ductal adenocarcinoma.

Tumor budding in intestinal-type gastric adenocarcinoma is associated with nodal metastasis and recurrence

“…Multiple series have shown that increased tumor budding is associated with lymph node metastasis, distant metastasis, and recurrence in colorectal adenocarcinomas [15,16]. Similar studies have also shown a similar relationship in adenocarcinomas of the ampulla [21], esophagus [22,23], and pancreas [24]. However, very little research has been performed evaluating tumor budding in GAC [18,25,26].…”

“…Because all cases were reviewed concurrently in our study, no assessment of interobserver agreement was practical. Only a subset of the published studies quantifies interobserver variability with kappa values ranging from moderate to very good [15,16,23,24,32,33]. P=0.07).…”

“…Given the wide variety of different methods employed in both colorectal carcinoma and upper gastrointestinal malignancies [15,16,18,21,22,24] that provide largely compatible results, it is reasonable to hypothesize that a single standardized method could be applied to carcinomas throughout the luminal gastrointestinal tract. Another potential pitfall in the assessment of tumor budding assessment is the need to ensure an acceptable level of interobserver variability.…”

High-Grade Tumor Budding Stratifies Early-Stage Cervical Cancer with Recurrence Risk

“…Morphologically, tumor budding is defined as the presence of single tumor cells or isolated small clusters of tumor cells (up to 5 tumor cells) scattered in the stroma at the invasive front; it represents a type of local diffusely infiltrative growth and occurs when tumor cells detach from the invasive tumor margin and migrate into the surrounding stroma. Tumor budding has frequently been observed in several types of solid tumors, including colorectal cancer [12], esophageal carcinoma [13], pancreatic carcinoma [14, 15], breast cancer [16, 17], lung carcinoma [18, 19], and endometrial carcinoma [20]; tumor budding has been recognized as an aggressive indicator and an adverse prognostic factor [12–20]. Moreover, as a result of its significant prognostic value, tumor budding is recommended by the International Union against Cancer for inclusion in the pathological report of colorectal cancer as an additional prognostic factor [21].…”

Tumour budding in pancreatic cancer revisited: validation of the ITBCC scoring system

“…Especially in aggressive PDAC, the invasive tumour margin includes the presence of de‐differentiated carcinoma cells detached from the main tumour and showing signs of epithelial–mesenchymal transition (EMT), identified histologically as ‘tumour budding’ (BD) . Recent studies have confirmed that an increasing number of tumour buds has a significant adverse impact on patient survival and have identified BD as an independent prognostic factor in PDAC . All these studies provided evidence for an improved prognostic stratification of PDAC patients based on the assessment of BD.…”