title: Ras p21 immunostaining in early stage squamous cervical carcinoma: relationship with lymph nodal involvement and 72 kDa-metalloproteinase index.
abstract: BACKGROUND
  Ras p21 expression seems to be associated with aggressiveness of neoplastic growth and metastatic potentially in human solid tumors. In our series of early-stage squamous cervical carcinoma, we evaluated ras p21 expression with respect to lymph nodal involvement; the aim was to analyse the ras p21 immunostaining as potential marker of lymphatic spread, and investigate the relationship between ras p21 expression and 72 kDa-metalloproteinase immunostaining.
  
  
  METHODS
  46 patients with FIGO stage I squamous cell cervical carcinoma, who had undergone primary radical surgery with systematic pelvic and paraaortic lymphadenectomy (Piver's type III) at the Institute of Gynecologic and Obstetrics, Ancona University, were recruited from our series of 59 consecutive cases, and included the study. Any characteristic that could be relevant for prognosis was recorded such as: histologic grade of differentiation, tumor size, lymphatic spread, or adjuvant radiotherapy. Immunohistochemical staining was performed using the avidin-biotin peroxidase complex method (LSAB, Dako, Copenhagen, Denmark). Monoclonal antibody anti-pan ras (Ab-1) (Oncogene Science) and affinity purified rabbit anti-72 kDa-metalloproteinase antibody were used. Positivity for ras p21 was evaluated by semiquantitative analysis, while 72 kDa-metalloproteinase staining was expressed as the percentage of positive cells per 10(3) counted neoplastic cells (index).
  
  
  RESULTS
  The expression of ras p21 was observed in 31 patients (67%) with FIGO stage I squamous cervical carcinoma. No connection was found between ras p21 expression and tumor size (P = 0.2), or histologic grade (P = 0.9), while a significant relationship was observed with respect to lymph nodal status (p = 0.048). By analysing 72 kDa-metalloproteinase immunostaining, ras p21 positive carcinomas showed significantly higher 72 kDa-metalloproteinase index than the negative ones (mean + standard deviation, 23.3% + 7.7% and 13.8% + 5.1% respectively, and P < 0.001).
  
  
  CONCLUSIONS
  Though the relatively small size of our series does not allow any definitive conclusion, a significant relationship between ras p21 expression and risk of lymphatic spread was detected in early-stage cervical carcinoma. ras p21 positivity seems to be an indicator of neoplastic aggressiveness and lymphatic spread, and is associated with significantly higher expression of 72 kDa-metalloproteinase.
authors.affiliation: Instituto di Clinica Ostetrica e Ginecologica, Università degli Studi di Ancona, Italy.
authors.forename: G G
authors.initials: GG
authors.lastname: Garzetti
authors.forename: A
authors.initials: A
authors.lastname: Ciavattini
authors.forename: G
authors.initials: G
authors.lastname: Lucarini
authors.forename: G
authors.initials: G
authors.lastname: Goteri
authors.forename: M D
authors.initials: MD
authors.lastname: Nictolis
authors.forename: C
authors.initials: C
authors.lastname: Romanini
authors.forename: G
authors.initials: G
authors.lastname: Biagini
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008666:Metalloendopeptidases / Q000378:metabolism*; D008875:Middle Aged; D015689:Oncogene Protein p21(ras) / Q000378:metabolism*; D012189:Retrospective Studies; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D008666:Metalloendopeptidases; D015689:Oncogene Protein p21(ras)