title: Clinicopathologic and molecular correlations of necrosis in the primary tumor of patients with renal cell carcinoma.
abstract: BACKGROUND
  The presence of histologic necrosis in the primary tumor of patients with renal cell carcinoma (RCC) has been suggested to be an important predictor of survival. The authors investigated the relation of tumor necrosis to other clinicopathologic factors known to be important prognostic indicators for patients with RCC.
  
  
  METHODS
  The records of 311 patients undergoing treatment for RCC were evaluated for basic clinicopathologic information including TNM classification, nuclear grade, Eastern Cooperative Oncology Group (ECOG) performance status (PS), disease recurrence, and survival. The presence and extent of histologic necrosis of the primary tumors was recorded and correlated with clinicopathologic factors, carbonic anhydrase IX and Ki-67 expression, disease recurrence, and survival.
  
  
  RESULTS
  The presence of necrosis in the primary tumor of patients with RCC compared with patients with RCC without necrosis was associated with higher T classification (P < 0.0001), the presence of lymph node disease (P = 0.009), the presence of metastases (P < 0.0001), higher grade (P < 0.0001), greater mean tumor size (P < 0.0001), an ECOG PS score > or = 1 (P = 0.007), higher University of California-Los Angeles Integrated Staging System (UISS) category (P < 0.0001), and higher Ki-67 expression (P < 0.0001). The extent of necrosis in the primary tumor was associated with the presence of lymph node disease (P = 0.009) and the presence of metastases (P < 0.0001), and correlated with higher T classification (sigma = 0.31, P < 0.0001), poorer ECOG PS (sigma = 0.18, P = 0.002), higher grade (sigma = 0.33, P < 0.0001), greater tumor size (sigma = 0.40, P < 0.0001), higher UISS category (sigma = 0.37, P < 0.0001), and higher Ki-67 staining (sigma = 0.32, P < 0.0001). Patients with the presence of necrosis in the primary tumor demonstrated a lower 5-year disease-specific survival compared with patients without necrosis in the primary tumor (36% vs. 75%; P < 0.0001). Multivariate analysis demonstrated that T classification (P < 0.0001), distant metastases (P < 0.0001), and ECOG PS (P < 0.0001) were independent predictors of DSS, whereas the presence of necrosis was not (P = 0.1100). Substratification into localized and metastatic disease demonstrated that the presence of necrosis was an independent predictor of survival in patients with localized (P = 0.025), but not metastatic (P = 0.44), disease. The extent of necrosis was not an independent predictor of survival (P > 0.05). Patients with the presence of necrosis in the primary tumor had a lower 5-year disease recurrence-free rate compared with patients without the presence of necrosis (62% vs. 92%, P < 0.0001).
  
  
  CONCLUSIONS
  The presence of necrosis in the primary tumor was associated with adverse prognostic factors such as high T classification, presence of lymph node disease and metastases, high grade, large tumor size, and poor ECOG PS. The extent of necrosis was found to be associated with the presence of lymph node disease and metastases and correlated with higher T classification, higher grade, greater tumor size, poorer ECOG PS, and higher UISS category. The presence of this histologic variant was an independent predictor of poor survival in patients with localized, but not metastatic, disease. In addition, Ki-67 expression served as a valuable surrogate marker for the presence of histologic tumor necrosis.
authors.affiliation: Department of Urology, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, California 90095-1738, USA.
authors.forename: John S
authors.initials: JS
authors.lastname: Lam
authors.forename: Oleg
authors.initials: O
authors.lastname: Shvarts
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Said
authors.forename: Allan J
authors.initials: AJ
authors.lastname: Pantuck
authors.forename: David B
authors.initials: DB
authors.lastname: Seligson
authors.forename: Michael E
authors.initials: ME
authors.lastname: Aldridge
authors.forename: Matthew H T
authors.initials: MH
authors.lastname: Bui
authors.forename: Xueli
authors.initials: X
authors.lastname: Liu
authors.forename: Steve
authors.initials: S
authors.lastname: Horvath
authors.forename: Robert A
authors.initials: RA
authors.lastname: Figlin
authors.forename: Arie S
authors.initials: AS
authors.lastname: Belldegrun
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002256:Carbonic Anhydrases / Q000378:metabolism; D002291:Carcinoma, Papillary / Q000378:metabolism / Q000473:pathology* / Q000556:secondary; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000473:pathology; D009367:Neoplasm Staging; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011379:Prognosis; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D009419:Nerve Tissue Proteins; D002256:Carbonic Anhydrases