ABSTRACT
BACKGROUND: Several mechanisms are involved in the development of resistance to therapy in locally advanced cervical squamous cell carcinoma (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 treated with different chemotherapy regimens. METHODS: 126 LACSCC patients at FIGO stages IIB-IVA were selected from the GOCS database: 74 patients included in 3 different prospective phase II trials in the neoadjuvant setting (vinorelbine, docetaxel, ifosfamide-vinorelbine-cisplatin) and 52 patients treated with standard radiochemotherapy based on 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. Tumors with expansive growth showed higher grade (p = 0.0024), mitotic index (p = 0.0505), tumor necrosis (p = 0.0191), LeY+ (p = 0.0034) and CD44+/LeY+ coexpression (p = 0.0334). CD44+ cells were present in 91.3% of patients with local recurrence (p = 0.0317). Advanced stage was associated with LeY+ tumors. Patients treated with RCBC had worse DFS and OS when their tumors expressed LeY (p = 0.0083 and p = 0.0137, 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 patients, the coexpression of CD44 and LeY was not associated with worse outcome. However, in the subgroup of patients receiving RCBC, LeY expression was correlated with shorter DFS and OS.
Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/immunology , Cisplatin/therapeutic use , Lewis Blood Group Antigens/immunology , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/immunology , Adult , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Female , Humans , Lewis Blood Group Antigens/genetics , Neoplasm Staging , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/pathologyABSTRACT
BACKGROUND: Several studies in solid tumors have shown that expression of excision repair cross-complementation group 1 (ERCC1) and class III ß-tubulin (TUBB3) can predict response to chemoradiotherapy and might be prognostic factors. We assessed the role of ERCC1 and TUBB3 expressions as predictive and prognostic factors in locally advanced cervical squamous cell carcinoma (LACSCC) patients treated with different neoadjuvant regimens. METHODS: ERCC1 and TUBB3 were detected in 88 patients with LACSCC by immunohistochemical analysis. Sixty-two patients were included in 3 different prospective trials and grouped as follows: vinorelbine or docetaxel (group A, n = 44) and ifosfamide-vinorelbine-cisplatin (group B, n = 18). Both groups were compared with standard cisplatin chemoradiotherapy (group C, n = 26). Clinical data at baseline, disease-free survival (DFS) and overall survival (OS) were also collected. Univariate and multivariate Cox models were used to analyze the risk factors. RESULTS: Thirty-five patients (39.8%) and 18 (20.5%) had high ERCC1 and TUBB3 expression, respectively. Both proteins were overexpressed in tumors with unfavorable characteristics. High ERCC1 was associated with advanced FIGO stage (p = 0.034) and progressive disease (49% vs. 28%). Poor DFS (p = 0.021) and OS (p = 0.005) were observed in group C patients with high ERCC1 expression. Multivariate analysis showed that ERCC1 expression, FIGO stage and pretreatment hemoglobin level were significant prognostic factors (p = 0.002, p = 0.008 and p = 0.005, respectively). CONCLUSIONS: ERCC1 expression could be a predictive and prognostic factor in LACSCC patients who receive cisplatin monotherapy. Conversely, TUBB3 had no impact on survival in patients treated with antimicrotubule agents.
Subject(s)
Carcinoma, Squamous Cell/metabolism , DNA-Binding Proteins/analysis , Endonucleases/analysis , Neoplasm Proteins/analysis , Tubulin/analysis , Uterine Cervical Neoplasms/metabolism , Adult , Aged , Antineoplastic Agents, Alkylating/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Brachytherapy , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/therapy , Chemoradiotherapy , Cisplatin/administration & dosage , Cisplatin/therapeutic use , Clinical Trials, Phase II as Topic , DNA-Binding Proteins/biosynthesis , Disease Progression , Disease-Free Survival , Endonucleases/biosynthesis , Female , Gene Expression Regulation, Neoplastic , Humans , Hysterectomy , Ifosfamide/administration & dosage , Kaplan-Meier Estimate , Mesna/administration & dosage , Middle Aged , Neoplasm Proteins/biosynthesis , Palliative Care , Prognosis , Radiotherapy, Adjuvant , Tubulin/biosynthesis , Uterine Cervical Neoplasms/mortality , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/therapy , Vinblastine/administration & dosage , Vinblastine/analogs & derivatives , VinorelbineABSTRACT
La incidencia de carcinomas en 700 colecistectomías fue de 5,4%. Se estudió la mucosa adyacente al tumor en 21 preparados histológicos correspondientes a carcinomas invasivos de la vesícula. Las lesiones proliferativas vecinas al tumor fueron 14 hiperplasias con displasia, 8 carcinomas in situ y 7 hiperplasias epiteliales. Se discute la posibilidad de que estas lesiones proliferativas se originen a partir de la litiasis y de la colecistitis crónica. En la mucosa se producen alteraciones progresivas donde las hiperplasias desarrollarían cambios atípicos que podrían concluir en un carcinoma. Por lo tanto estas lesiones pueden ser consideradas potencialmente neoplásicas
Subject(s)
Aged , Middle Aged , Humans , Gallbladder Neoplasms/surgery , Gallbladder/pathology , Cholecystectomy , HyperplasiaABSTRACT
La incidencia de carcinomas en 700 colecistectomías fue de 5,4%. Se estudió la mucosa adyacente al tumor en 21 preparados histológicos correspondientes a carcinomas invasivos de la vesícula. Las lesiones proliferativas vecinas al tumor fueron 14 hiperplasias con displasia, 8 carcinomas in situ y 7 hiperplasias epiteliales. Se discute la posibilidad de que estas lesiones proliferativas se originen a partir de la litiasis y de la colecistitis crónica. En la mucosa se producen alteraciones progresivas donde las hiperplasias desarrollarían cambios atípicos que podrían concluir en un carcinoma. Por lo tanto estas lesiones pueden ser consideradas potencialmente neoplásicas (AU)
