CD44 isoform 6 (CD44v6) is a prognostic indicator of the response to neoadjuvant chemotherapy in cervical carcinoma

Objective. The clinical efficacy of neoadjuvant chemotherapy (NAC) in disti nct groups of cervical cancer patients has been well documented, but parame ters at the cellular level regulating the different responsiveness to this treatment have not been adequately explored. Method. A series of 21 patients with stage Ib and IIa bulky cervical carcin omas were treated by preoperative NAC with three courses of cisplatin, epir ubicin, etoposide, and bleomycin prior to radical hysterectomy, and subsequ ently followed up for a mean of 52.3 months. Biopsies taken prior to NAG an d operative specimens were subjected to immunohistochemical (IHG) staining for alpha -catenin, beta -catenin, E-cadherin, and CD44 isoform 6 (CD44v6), to uncover the role of adhesion molecules as determinants of the response to NAG and disease outcome. Results. Seven of the twenty-one (33.3%) women died of the disease; adenosq uamous (n = 4 cases) histology (RR 4.50, 95% CI 1.85-10.68) and lymph node involvement (RR 6.00, 95% CI0.42-85.26) were significant determinants of no nsurvival. All 21 carcinomas were human papillomavirus DNA positive. The fa ctors predicting the response to NAC in univariate analysis were: GD44v6 ex pression in the pre-NAG and post-NAG samples (P = 0.00056 and P = 0.00336, respectively). In multiple logistic regression analysis, the factors with i ndependent predictive value for response to NAC were GD44v6 expression prio r to (P = 0.0099) and after (P = 0.0470) NAG. In univariate survival analys is, the most significant (P < 0.001) predictors of recurrence-free survival (RFS) were age and number of lymph nodes removed. In multivariate survival analysis, the independent predictor for RFS was only histological type (P = 0.0064). Overall survival (OS) was predicted in a Cox model by recurrence (P = 0.0033), CD44v6 expression after NAG (P = 0.013), and patient's age ( P = 0.039). Conclusions. These data indicate that GD44v6 is involved in the response to NAG, and eventually in disease outcome. This implicates that the assessmen t of CD44v6 expression might help in selecting patients who are likely to r espond to NAG, i.e., women with significantly reduced CD44v6 expression in their tumors before treatment. Noteworthy, the response to NAG did not pred ict a favorable disease outcome, (C) 2001 Academic Press.