title: Expression of Cathepsin L in tumor cells and tumor-associated macrophages in patients with Ewing sarcoma family of tumors: a pilot study.
abstract: BACKGROUND
  Cysteine protease Cathepsin L is involved in bone remodeling and expressed in activated macrophages. It is highly expressed in metastatic tumor tissue, especially with bone metastases.
  
  
  OBJECTIVE
  We evaluated immunohistochemical expression of Cathepsin L in tumor cells and tumor-associated macrophages (TAMs) in chemo-naive Ewing sarcoma.
  
  
  METHODS
  Retrospective evaluation of archived specimens of Ewing sarcoma.
  
  
  METHODS
  Immunohistochemical staining was performed on archived blocks of chemo-naive patients with Ewing sarcoma treated with uniform chemotherapy at our institute between January 2009 and November 2011.
  
  
  METHODS
  Immunohistochemical expression was co-related with baseline demographics and survival.
  
  
  RESULTS
  During the study period, we had evaluable baseline samples from 62 patients with median age 15 years (range: 2-40); 26 (42%) had metastases. Cathepsin L expression in tumor cells was observed in 8/62 (13%) specimens. None of the baseline clinical characteristics correlated with Cathepsin L expression. Cathepsin L positivity was associated with poor response to neoadjuvant chemotherapy (NACT) (P = 0.05), but did not influence either event-free-survival (EFS) or overall survival. Cathepsin L was expressed in TAMs in all specimens. Grade 3 TAMs (>10 TAMs/high power field) was associated with better response to NACT (P = 0.05). On univariate analysis Grade 3 TAMs predicted superior EFS (median EFS 28.5 months in those with Grade 3 TAMs versus 14.8 months in those with grade ½ TAMs [P = 0.04]).
  
  
  CONCLUSIONS
  Cathepsin L expression by immunohistochemistry was low in our patient cohort, and it did not affect the outcome. In addition, Grade 3 TAMs with Cathepsin L expression was associated with improved EFS.
authors.forename: Bivas
authors.initials: B
authors.lastname: Biswas
authors.forename: Mehar Chand
authors.initials: MC
authors.lastname: Sharma
authors.forename: Asit Ranjan
authors.initials: AR
authors.lastname: Mridha
authors.affiliation: Department of Medical Oncology, Dr. B. R. Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.
authors.forename: Sameer
authors.initials: S
authors.lastname: Bakhshi
mesh_terms: D000293:Adolescent; D000328:Adult; D056668:Cathepsin L / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000737:chemistry*; D008297:Male; D010865:Pilot Projects; D011379:Prognosis; D012189:Retrospective Studies; D012512:Sarcoma, Ewing / Q000473:pathology*; D055815:Young Adult
chemical_list: D056668:Cathepsin L