title: Tumor Budding Detection by Immunohistochemical Staining is Not Superior to Hematoxylin and Eosin Staining for Predicting Lymph Node Metastasis in pT1 Colorectal Cancer.
abstract: BACKGROUND
  Tumor budding is recognized as an important risk factor for lymph node metastasis in pT1 colorectal cancer. Immunohistochemical staining for cytokeratin has the potential to improve the objective diagnosis of tumor budding over detection based on hematoxylin and eosin staining. However, it remains unclear whether tumor budding detected by immunohistochemical staining is a significant predictor of lymph node metastasis in pT1 colorectal cancer.
  
  
  OBJECTIVE
  The purpose of this study was to clarify the clinical significance of tumor budding detected by immunohistochemical staining in comparison with that detected by hematoxylin and eosin staining.
  
  
  METHODS
  This was a retrospective study.
  
  
  METHODS
  The study was conducted at Niigata University Medical & Dental Hospital.
  
  
  METHODS
  We enrolled 265 patients with pT1 colorectal cancer who underwent surgery with lymph node dissection.
  
  
  METHODS
  Tumor budding was evaluated by both hematoxylin and eosin and immunohistochemical staining with the use of CAM5.2 antibody. Receiver operating characteristic curve analyses were conducted to determine the optimal cutoff values for tumor budding detected by hematoxylin and eosin and CAM5.2 staining. Univariate and multivariate analyses were performed to identify the significant factors for predicting lymph node metastasis.
  
  
  RESULTS
  Receiver operating characteristic curve analyses revealed that the cutoff values for tumor budding detected by hematoxylin and eosin and CAM5.2 staining for predicting lymph node metastases were 5 and 8. On multivariate analysis, histopathological differentiation (OR, 6.21; 95% CI, 1.16-33.33; p = 0.03) and tumor budding detected by hematoxylin and eosin staining (OR, 4.91; 95% CI, 1.64-14.66; p = 0.004) were significant predictors for lymph node metastasis; however, tumor budding detected by CAM5.2 staining was not a significant predictor.
  
  
  CONCLUSIONS
  This study was limited by potential selection bias because surgically resected specimens were collected instead of endoscopically resected specimens.
  
  
  CONCLUSIONS
  Tumor budding detected by CAM5.2 staining was not superior to hematoxylin and eosin staining for predicting lymph node metastasis in pT1 colorectal cancer.
authors.affiliation: 1 Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan 2 Department of Surgery, Niigata Cancer Center Hospital, Niigata, Japan 3 Division of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Okamura
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Shimada
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nogami
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kameyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Kosugi
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Wakai
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ajioka
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D004396:Coloring Agents; D004801:Eosine Yellowish-(YS); D005260:Female; D006416:Hematoxylin; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000378:metabolism*; D016015:Logistic Models; D008197:Lymph Node Excision; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D012372:ROC Curve; D012189:Retrospective Studies
chemical_list: D015415:Biomarkers; D014408:Biomarkers, Tumor; C400901:CAM 5.2 antigen; D004396:Coloring Agents; D007633:Keratins; D004801:Eosine Yellowish-(YS); D006416:Hematoxylin