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Prognostic Significance Of COX-2、 Ki-67、 Cyclin A、 P27 And Chemoradiation In Patients With Esophageal Squamous Cell Carcinoma

Posted on:2012-05-09Degree:DoctorType:Dissertation
Country:ChinaCandidate:J X HuangFull Text:PDF
GTID:1224330368491174Subject:Digestive science
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PartⅠPrognostic significance of COX-2、Ki-67、cyclin A、p27 in patients with esophageal squamous cell carcinomaObjective: The aim of this study was to observe the correlation of the expression of the molecular markers cyclooxygenase-2(COX-2), Ki-67, cyclin A, p27, clinicopathological features and survival in patients with esophageal squamous cell carcinoma (ESCC), to assess the additional prognostic value of these proteins for them.Methods: To be selected for this retrospective study, all specimens were obtained from patients who had not received chemotherapy or radiotherapy prior to surgical resection. Five cases were Stage I, 38 cases were Stage II, 26 cases were StageⅢ, and 9 cases were StageⅣ. The expression levels of COX-2, Ki-67, cyclin A and p27 proteins were studied in a series of 78 primarily resected ESCC samples by immunohisto -chemistry method. Cox proportional hazards model was used to analyze the association of the clinicopathologic variables and biomarkers (cyclin A and Ki-67, p27 and COX-2 expression) with metastases free survival and overall survival. Variables significantly associated with survival in univariate Cox models were included into multivariate Cox model. The results were quantified by calculating hazard ratios (HR) with 95% confidence intervals (95% CI). Survival curves were calculated using Kaplan-Meier method and the differences between the curves were determined with log-rank test.Results: A total of 78 specimens were included in this study. Expression of COX-2 was observed in 43(55.1%)cases, and high levels of expression of Ki-67, p27 and cyclin A were observed in 57(73.0%), 33(42.3%), 43(55.1%) cases, respectively. The survival rate of three years was 49.7%. On univariate survival analysis, more advanced tumor stage, mediastinal lymph node involvement, systemic dissemination, the level of expression of COX-2, Ki-67, cyclin A and p27 were found to be associated with survival (all P value<0.05); but no difference in the survival rate was observed between different sexes, with different locations of cancer, age, differentiation. Multifactorial survival analysis revealed that only mediastinal lymph node involvement, overexpression of cyclin A and low p27 expression were associated with the survival of the patients (HR=2.83, 4.7, 2.99, respectively; P=0.025, 0.042, 0.005, respectively). For 3-year Kaplan-Meier estimates significant survival differences (positive versus negative) included: lymph node involvement (18% versus 65%), p27 (70.7% versus 34.5%), and cyclin A (29.6% versus 74.5%), P value<0.05.Conclusions: Mediastinal lymph node involvement, the immunohistochemical expression of cell proliferation markers cyclin A and p27 may be used as independent prognostic factors for patients with ESCC, whereas neither COX-2 nor Ki-67 is of prognostic value.PartⅡResponses of esophageal squamous cell carcinoma to chemoradiotherapy and prognostic factors: a report of 77 casesObjective: This study was to observe the responses of esophageal squamous cell carcinoma (ESCC) to chemoradiotherapy, and to analyze its probable prognostic factors.Methods: A retrospective analysis of 77 ESCC patients treated with chemoradiotherapy between 2004 and 2008 in The People’s Hospital of Taizhou was performed with documentation of treatment given, toxicities recorded, and follow-up and outcome data. Those deemed unsuitable for surgery on the grounds of performance status, bulky local disease or personal choice received chemoradiotherapy. ESCC were confirmed histologically or pathologically. Of the 77 patients, 48 cases were treated with﹤2 cycles of chemotherapy together with radiotherapy, 23 cases were treated with≥2 cycles of chemotherapy together with radiotherapy, 6 cases were treated with chemotherapy alone. Survival curves were calculated using Kaplan-Meier method and the differences between the curves were determined with log-rank test. Variables significantly associated with survival in univariate Cox models were included into multivariate Cox model. The results were quantified by calculating hazard ratios (HR) with 95% confidence intervals (95% CI).Results: The response rate of 77 patients was 79.2% (61/77). The median survival time was 17 months. 1- year,2-year and 3-year survival rates were 68.1%、36.3%、23.8%, respectively. The median survival time in patients with≥2 cycles of chemotherapy together with radiotherapy group was significant longer than the patients with﹤2 cycles of chemotherapy together with radiotherapy group and chemotherapy alone group (35 months、13 months and 8 months, respectively, P﹤0.05); for three groups, 1- year survival rates were 78.7%、60.2% and 34.5% (P﹤0.05), respectively, 3-year survival rates were 34.6%、22.6% and 0 (P﹤0.05) , respectively. Univariate analysis indicated that the location of tumor, mediastinal lymph node metastasis and systemic dissemination, the scheme of treatment and short-term efficacy were significant prognostic factors(P﹤0.05); but no difference in the survival rate was observed between different sexes, age. Multifactorial survival analysis suggested that only mediastinal lymph node involvement and systemic dissemination were associated with the survival of the patients (HR=2.48,2.71, respectively; 95%CI=1.227~5.027, 1.341~5.459, respectively; P﹤0.05,P﹤0.01, respectively).Conclusions: The response rate may be significantly higher in patients with≥2 cycles of chemotherapy together with radiotherapy group than in patients with﹤2 cycles of chemotherapy together with radiotherapy group and chemotherapy alone group. Mediastinal lymph node involvement and systemic dissemination may be used as independent prognostic factors for patients with esophageal squamous cell carcinoma after chemoradiotherapy treatment.
Keywords/Search Tags:Cyclooxygenase - 2, Cyclin A, P27, Esophageal neoplasm, Prognosis, Esophageal neoplasm, Chemotherapy, Radiotherapy, Efficacy, Prognostic factors
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