title: Assessment of microvessel density and carbonic anhydrase-9 (CA-9) expression in rectal cancer.
abstract: OBJECTIVE
  The mechanism by which neoplasias respond to hypoxia determines their biological behavior and prognosis. Understanding the biology of tumors under hypoxic conditions is crucial for the development of anti-angiogenic therapy. Using the largest cohort of rectal adenocarcinomas to date, this study aimed to assess microvessel density (MVD) and carbonic anhydrase-9 (CA-9) expression and to correlate the results with recurrence and cancer-specific survival.
  
  
  METHODS
  Patients (n=101) who underwent surgery for rectal adenocarcinoma without previous neoadjuvant therapy or metastatic disease were selected. MVD and CA-9 expression were assessed immunohistologically by using the CD34 antibody and the MN/CA9 M75 antibody, respectively. In a multifactorial analysis, the results were correlated with tumor stage, recurrence rate, and long-term survival.
  
  
  RESULTS
  MVD was higher with increased T- and N-stages (p<0.01) and associated positively with poor survival (hazard ratio (HR) 1.3 per 10 vessel increase, p<0.01). CA-9 was expressed in 73% of cancers. Negative lymph node status correlated with CA-9 positivity (p<0.05), reflected in a higher rate of CA-9 positivity in earlier Dukes' stages (p<0.05). CA-9 positivity across tumor node metastasis (TNM) stages approached significance (Stage I/II: 80% CA-9 positive vs. 20% CA-9 negative; Stage III: 63% CA-9 positive vs. 37% negative, p=0.051). A trend was seen towards better cancer-specific survival in patients with CA-9 positive carcinomas (HR 0.51, p=0.07) on univariate analysis.
  
  
  CONCLUSIONS
  MVD was higher in more advanced T- and N-stages and may be used as a determinant of survival in patients with rectal adenocarcinomas. CA-9 expression was seen more often in earlier Dukes' stages, possibly representing an early tumor hypoxic response. CA-9 expression by adenocarcinoma cells may confer long-term survival advantage in surgically treated rectal cancer.
authors.affiliation: Department of Surgery, St Mark's Hospital, Harrow, Middlesex, UK.
authors.forename: S
authors.initials: S
authors.lastname: Rasheed
authors.forename: A L
authors.initials: AL
authors.lastname: Harris
authors.forename: P P
authors.initials: PP
authors.lastname: Tekkis
authors.forename: H
authors.initials: H
authors.lastname: Turley
authors.forename: A
authors.initials: A
authors.lastname: Silver
authors.forename: P J
authors.initials: PJ
authors.lastname: McDonald
authors.forename: I C
authors.initials: IC
authors.lastname: Talbot
authors.forename: R
authors.initials: R
authors.lastname: Glynne-Jones
authors.forename: J M A
authors.initials: JM
authors.lastname: Northover
authors.forename: T
authors.initials: T
authors.lastname: Guenther
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply* / Q000201:enzymology* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000368:Aged; D000951:Antigens, Neoplasm / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000032:analysis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D055806:Microvessels / Q000473:pathology*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D012004:Rectal Neoplasms / Q000098:blood supply* / Q000201:enzymology* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D012008:Recurrence; D018570:Risk Assessment; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases