title: The expression of CYP2W1 in colorectal primary tumors, corresponding lymph node metastases and liver metastases.
abstract: BACKGROUND
  Metastatic disease is a major cause of death in patients with colorectal cancer (CRC). We have previously investigated expression of an orphan cytochrome P450 (CYP) enzyme, CYP2W1, and found high expression in about one third of colorectal tumors. CYP2W1 has proven to metabolize duocarmycin analogs into cytotoxic substances, compounds that in xenografts of CRC cells expressing CYP2W1 completely inhibit tumor growth. This study was designed to evaluate whether the enzyme is expressed in primary CRC and corresponding metastases.
  
  
  METHODS
  Samples from primary tumors, corresponding lymph node metastases and liver metastases from 96 patients were collected and analyzed by immunohistochemistry. Data regarding patient's demographics, tumor characteristics and survival were also collected.
  
  
  RESULTS
  Out of 96 patients, 25 (26%) had high CYP2W1 expression in the primary tumor and 46 (48%) showed high levels in the liver metastasis. In total 59 patients had lymph node metastases, and 31% of them had high CYP2W1 expression. When comparing the expression in primary tumor with that of the first liver metastasis, the increase in expression was statistically significant (p = 0.005).
  
  
  CONCLUSIONS
  High CYP2W1 expression is seen in 26% of primary CRC and in 48% of corresponding liver metastases. This opens possibilities for new targeted therapies to metastatic CRC in the future.
authors.affiliation: Center of Surgical Gastroenterology, Karolinska University Hospital , Stockholm , Sweden.
authors.forename: Kristina
authors.initials: K
authors.lastname: Stenstedt
authors.forename: Marja
authors.initials: M
authors.lastname: Hallstrom
authors.forename: Frida
authors.initials: F
authors.lastname: Lédel
authors.forename: Peter
authors.initials: P
authors.lastname: Ragnhammar
authors.forename: Magnus
authors.initials: M
authors.lastname: Ingelman-Sundberg
authors.forename: Inger
authors.initials: I
authors.lastname: Johansson
authors.forename: David
authors.initials: D
authors.lastname: Edler
mesh_terms: D000368:Aged; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D000072467:Cytochrome P450 Family 2; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000556:secondary*; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis
chemical_list: D003577:Cytochrome P-450 Enzyme System; C509336:CYP2W1 protein, human; D000072467:Cytochrome P450 Family 2