Relevant Role of Di-Fucosylated Ley Antigen in the Outcome of Locally Advanced Cervical Squamous Cell Carcinoma Patients Treated with Cisplatin Regimen

Zwenger Ao,Leone Jp ,Vallejo Ct ,Pérez Je ,Mac Donnell ,Julieta Leone ,Domínguez Me ,Julián Iturbe ,G Grosman ,Bernardo Amadeo Leone

doi:10.4172/2161-1025.1000156

Abstract

Background: Several mechanisms are involved in the development of resistance to therapy in LACSCC. Studies have shown that CD44 and Lewis Y antigen (LeY) form a complex that is associated with chemoresistance, tumor invasion and metastasis. We assessed the role of CD44 and LeY in the outcome of LACSCC patients (pts) treated with different chemotherapy regimens. Methods: A total of 126 LACSCC pts FIGO stages IIB-IVA were selected from GOCS databases: 74 pts included in three different prospective phase II trials in the neoadjuvant setting (vinorelbine, docetaxel, ifosfamide-vinorelbinecisplatin) and 52 pts treated with standard radio-chemotherapy based in cisplatin (RCBC). Clinical data at baseline, disease free survival (DFS) and overall survival (OS) were recorded. Univariate and multivariate Cox models were employed. Results: Median age was 45.6 years (range: 24.9 - 80.5). Sixty-three and 47 tumors were CD44+ and LeY+, respectively. Expansive growth tumors showed a higher grade (p=.0024), mitotic index (p=.0505), tumoral necrosis (p=.0191), LeY+ (p=.0034) and CD44+/LeY+ co-expression (p=.0334). CD44+ cells were present in 91.3% of those with local recurrence (p=.0317). Advanced stage was associated with LeY+ tumors (p=.0057). Pts treated with RCBC had worse DFS and OS when their tumors expressed LeY antigen (p=.0083 and p=.0137, respectively). Pre-treatment hemoglobin level, FIGO stage and tumor response remained the most significant prognostic factors in Cox regression. Conclusions: In our cohort of LACSCC pts, the co-expression of CD44+/LeY+ was not associated with worse outcome. However, in the subgroup of pts receiving RCBC, LeY expression was correlated with shorter DFS and OS.

Highlights

Cervical cancer is one of the most frequent malignancies in women and a considerable cause of morbidity and mortality
The aim of this study is to evaluate the role of CD44 and Lewis Y antigen (LeY) antigen in the outcome locally advanced cervical squamous cell carcinoma (LACSCC) patients
Univariate analysis showed that hemoglobin level lower than 115 mg/dl, advanced stages, expansive tumoral pattern, treatment and poor response by UICC criteria were related with worse disease free survival (DFS) and overall survival (OS)

Summary

Introduction

Cervical cancer is one of the most frequent malignancies in women and a considerable cause of morbidity and mortality. Each year approximately 500,000 women around world are diagnosed with invasive cervical cancer and more than half of them die from their disease. Eighty percent of these deaths occur in developing countries. The development of resistance to chemo- or radio-therapy involves multiples mechanisms in locally advanced cervical squamous cell carcinoma (LACSCC). One of them could be the presence of a subpopulation of cells with regenerative abilities under cytotoxic stress Such cancer stem or clonogenic cells tend to repopulate tumors during the course of chemo- or radiotherapy [2,3]. We assessed the role of CD44 and LeY in the outcome of LACSCC patients (pts) treated with different chemotherapy regimens

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