title: CD44 isoform 6 (CD44v6) is a prognostic indicator of the response to neoadjuvant chemotherapy in cervical carcinoma.
abstract: OBJECTIVE
  Theclinical efficacy of neoadjuvant chemotherapy (NAC) in distinct groups of cervical cancer patients has been well documented, but parameters at the cellular level regulating the different responsiveness to this treatment have not been adequately explored.
  
  
  METHODS
  A series of 21 patients with stage Ib and IIa bulky cervical carcinomas were treated by preoperative NAC with three courses of cisplatin, epirubicin, etoposide, and bleomycin prior to radical hysterectomy, and subsequently followed up for a mean of 52.3 months. Biopsies taken prior to NAC and operative specimens were subjected to immunohistochemical (IHC) 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 NAC and disease outcome.
  
  
  RESULTS
  Seven of the twenty-one (33.3%) women died of the disease; adenosquamous (n = 4 cases) histology (RR 4.50, 95% CI 1.85-10.68) and lymph node involvement (RR 6.00, 95% CI 0.42-85.26) were significant determinants of nonsurvival. All 21 carcinomas were human papillomavirus DNA positive. The factors predicting the response to NAC in univariate analysis were: CD44v6 expression in the pre-NAC and post-NAC samples (P = 0.00056 and P = 0.00336, respectively). In multiple logistic regression analysis, the factors with independent predictive value for response to NAC were CD44v6 expression prior to (P = 0.0099) and after (P = 0.0470) NAC. In univariate survival analysis, 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 NAC (P = 0.013), and patient's age (P = 0.039).
  
  
  CONCLUSIONS
  These data indicate that CD44v6 is involved in the response to NAC, and eventually in disease outcome. This implicates that the assessment of CD44v6 expression might help in selecting patients who are likely to respond to NAC, i. e., women with significantly reduced CD44v6 expression in their tumors before treatment. Noteworthy, the response to NAC did not predict a favorable disease outcome.
authors.affiliation: Department of Obstetrics and Gynecology, St. Orsola-Malpighi Hospital, Bologna, Italy. SCOSTA@MED.UNIBO.IT
authors.forename: S
authors.initials: S
authors.lastname: Costa
authors.forename: P
authors.initials: P
authors.lastname: Terzano
authors.forename: A
authors.initials: A
authors.lastname: Bovicelli
authors.forename: A
authors.initials: A
authors.lastname: Martoni
authors.forename: B
authors.initials: B
authors.lastname: Angelelli
authors.forename: D
authors.initials: D
authors.lastname: Santini
authors.forename: C
authors.initials: C
authors.lastname: Ceccarelli
authors.forename: P
authors.initials: P
authors.lastname: Lipponen
authors.forename: M
authors.initials: M
authors.lastname: Erzén
authors.forename: S
authors.initials: S
authors.lastname: Syrjänen
authors.forename: K
authors.initials: K
authors.lastname: Syrjänen
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000276:immunology / Q000601:surgery; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001761:Bleomycin / Q000008:administration & dosage; D015820:Cadherins / Q000378:metabolism; D018196:Carcinoma, Adenosquamous / Q000188:drug therapy / Q000276:immunology / Q000601:surgery; D002945:Cisplatin / Q000008:administration & dosage; D003598:Cytoskeletal Proteins / Q000378:metabolism; D018572:Disease-Free Survival; D015251:Epirubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D007044:Hysterectomy; D007150:Immunohistochemistry; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D015996:Survival Rate; D015534:Trans-Activators; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000601:surgery; D051178:alpha Catenin; D051176:beta Catenin
chemical_list: D014408:Biomarkers, Tumor; C112697:CD44v6 antigen; C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D006023:Glycoproteins; D018960:Hyaluronan Receptors; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D001761:Bleomycin; D015251:Epirubicin; D005047:Etoposide; D002945:Cisplatin