RAS P21 IMMUNOSTAINING IN EARLY-STAGE SQUAMOUS CERVICAL-CARCINOMA - RELATIONSHIP WITH LYMPH NODAL INVOLVEMENT AND 72-KDA-METALLOPROTEINASE INDEX

Background: ras p21 expression seems to be associated with aggressiven ess of neoplastic growth and metastatic potentiality in human solid tu mors. In our series of early-stage squamous cervical carcinoma, we eva luated 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 ms p21 expre ssion and 72 kDa-metalloproteinase immunostaining. Patients and Method s: 46 patients with FIGO stage I squamous cell cervical carcinoma, who had undergone primary radical surgery with systematic pelvic and para aortic lymphadenectomy (Fiver's type III) at the Institute of Gynecolo gic and Obstetrics, Ancona University, were recruited from our series of 59 consecutive cases, and included the study. Any characteristic th at could be relevant for prognosis was recorded such as: histologic gr ade of differentiation, tumor size, lymphatic spread or adjuvant radio therapy. Immunohistochemical staining was performed using the avidin-b iotin peroxidase complex method (LSAB, Dako, Copenhagen, Danmark). Mon oclonal antibody anti-pan ras (Ab-l) (Oncogene Science) and affinity p urified rabbit anti-72 kDa-metalloproteinase antibody were used Positi vity for ms p21 was evaluated by semiquantitative analysis; while 72 k Da-metalloproteinase staining was expressed as the percentage of posit ive cells per 10(3) counted neoplastic cells (index). Results: The exp ression of ras p21 was observed in 31 patients (67%) with FIGO stage I squamous cervical carcinoma. No connection was found between ms p21 e xpression and tumor size (P=0.2), or histologic grade (P=0.9) while a significant relationship was observed with respect to lymph nodal stat us (p=0.048). By analysing 72 kDa-metalloproteinase immunostaining, ra s p21 positive carcinomas showed significantly higher 72 kDa-metallopr oteinase index than the negative ones (mean + standard deviation, 23.3 % + 7.7% and 13.8% + 5.1% respectively, and P<0.001). Conclusions: Tho ugh the relatively small size of our series does not allow any definit ive conclusion, a significant relationship between ms p21 expression a nd risk of lymphatic spread was detected in early-stage cervical carci noma. ras p21 positivity seems to be an indicator of neoplastic aggres siveness and lymphatic spread and is associated with significantly hig her expression of 72 kDa-metalloproteinase.