title: Immunohistochemically demonstrated lymph node micrometastasis and prognosis in patients with gallbladder carcinoma.
abstract: OBJECTIVE
  To investigate whether immunohistochemically demonstrated lymph node micrometastasis has a survival impact in patients with advanced gallbladder carcinoma (pT2-4 tumors).
  
  
  BACKGROUND
  The clinical significance of immunohistochemically detected lymph node micrometastasis recently has been evaluated in various tumors. However, few reports have addressed this issue with regard to gallbladder carcinoma.
  
  
  METHODS
  A total of 1476 lymph nodes from 67 patients with gallbladder carcinoma (pN0, n = 40; pN1, n = 27) who underwent curative resection were immunostained with monoclonal antibody against cytokeratins 8 and 18. The results were correlated with clinical and pathologic features and with patient survival.
  
  
  RESULTS
  Lymph node micrometastases were detected immunohistochemically in 23 (34.3%) of the 67 patients and in 37 (2.5%) of the 1476 nodes examined. Of the 37 nodal micrometastases, 21 (56.8%) were single-cell events, and the remaining 16 were clusters. Five micrometastases were detected in the paraaortic nodes. Clinicopathologic features showed no significant associations with the presence of lymph node micrometastases. Survival was worse in the 27 patients with pN1 disease than in the 40 with pN0 disease (5-year survival; 22.2% vs. 52.6%, P = 0.0038). Similarly, survival was worse in the 23 patients with micrometastasis than in the 44 without micrometastasis (5-year survival; 17.4% vs. 52.7%, P = 0.0027). Twenty-eight patients without any lymph node involvement had the best prognosis, whereas survival for the 11 patients with both types of metastasis was dismal. The grade of micrometastasis (single-cell or cluster) had no effect on survival. The Cox proportional hazard model identified perineural invasion, lymph node micrometastasis, and microscopic venous invasion as significant independent prognostic factors.
  
  
  CONCLUSIONS
  Lymph node micrometastasis has a significant survival impact in patients with pN0 or pN1 gallbladder carcinoma who underwent macroscopically curative resection. Extensive lymph node sectioning with keratin immunostaining is recommended for accurate prognostic evaluation for patients with gallbladder carcinoma.
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Sasaki
authors.forename: Masato
authors.initials: M
authors.lastname: Nagino
authors.forename: Tomoki
authors.initials: T
authors.lastname: Ebata
authors.forename: Koji
authors.initials: K
authors.lastname: Oda
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Arai
authors.forename: Hideki
authors.initials: H
authors.lastname: Nishio
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nimura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000175:diagnosis* / Q000401:mortality / Q000556:secondary*; D005260:Female; D005706:Gallbladder Neoplasms / Q000401:mortality / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000032:analysis*; D008198:Lymph Nodes / Q000737:chemistry*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D007633:Keratins