| Objective:Recently, neoadjuvant chemotherapy (NACT) followed by radical surgery hysterectomy plus pelvic lymph node dissection has emerged as a valid alternative in treating the locally advanced cervical cancer. However, not all patients can benefit from the NACT. Many cell biological markers have been studied in relation to survival and/ or response to chemotherapy, especially the apoptotic proteins. The 4 apoptosis proteins, Smac, Survivin, XIAP and Omi/HtrA2 have been demonstrated to induce sensitivity or resistance to chemotherapy in a variety of cancers except cervical carcinoma. The aim of this study was to evaluate the significance of Smac, Survivin, XIAP and Omi/HtrA2 protein expression to predict response to neoadjuvant chemotherapy and prognostic significance of these protein expressions in cervical cancer patients.Methods:From January 2004 to November 2013,73 patients diagnosed with FIGO stage IB-IIA cervical carcinoma at Cancer Hospital of Chinese Academy of Medical Sciences for whom receive a neoadjuvant platinum-based chemotherapy were included in the study. In the present study, immunohistochemistry was used to confirm the 4 apoptosis proteins, Smac, Survivin, Omi/HtrA2 and XIAP in pre- and post-chemotherapy tissues from chemotherapy-response and non-response cervical cancer patients. Two pathologists scored the results independently based on the intensity of staining and the extent of expression.Results:52 patients were identified as chemotherapy-response and 21 were non-response. The distribution of some clinical-pathological elements, including age, pathologic grade, pathology type etc, has no statistical difference between two groups (P>0.05, respectively). This study found that the expression of Survivin is statistically higher, while that of Omi/HtrA2 is significantly lower in the nonresponse group than that in the response group (P= 0.016, P=0.018). However, the tumor expression of Smac and XIAP did not display any significant differences between two groups (P>0.05). In the non-response group, expression of Smac and Omi/HtrA2 was increased (P=0.017, P=0.035), but Survivin was decreased after exposure to chemotherapy (P=0.025). No correlation was observed between the expression levels of Smac, Survivin and Omi/HtrA2 and the clinical factors, including age, FIGO grade, pathology type etc (P>0.05), however, the study found XIAP was correlated with Differentiation(P=0.027). What’s more, the expression of Smac and Omi/HtrA2 is positive correlation in cervical cancer tissues (r=0.293, P=0.003). In the study, median survival period of patients was 65 months, during the follow-up period, total 31 cases developed recurrence and 26 died of recurrence. The 2-year OS rates is 78.6% and 2-year PFS rate is 75.7%. Survival analysis revealed that chemo-sensitivity was an independent prognostic factor for OS and PFS of cervical cancer patients ((P=0.020, P=0.047).Conclusions:The present study indicated that the low-expression of Survivin, and the high-expression of Omi/HtrA2 in response-chemotherapy cervical carcinoma suggest significantly increased chemo-sensitivity in cervical cancer. Anti-apoptotic protein and pro-apoptotic protein take an important role in the progress of chemotherapy, and Smac may had a cooperative relation with Omi/HtrA2, which led to carcinogenesis and chemotherapy resistance. chemo-sensitivity has been an important prognostic factor for cervical cancer patients.Objective:To approach the clinical-pathological characteristics, treatment modalities and prognosis of patients with double primary carcinoma of endometrial carcinoma and colorectal carcinoma, and compare it with the patients with Lynch syndrome.Methods:The clinicopathologic and follow-up data of 34 cases with double primary carcinoma of endometrial carcinoma and colorectal carcinoma treated in Cancer Hospital of Chinese Academy of Medical Sciences from Jan.1991 to Dec.2012, were reviewed and analyzed retrospectively, and review the studies about Lynch syndrome.Result:The median age of 34 patients was 51.5 years old (ranging from 39 to 76), the median period between two cancers is 50 months.22 cases (64.7%) had at least one first-degree relative who had tumor and 8 cases had two first-degree relatives who had tumor. The pathological results indicated that 79.4%(27/34)was endometrioid adenocarcinoma and 55.9%(19/34) was colorectal adenocarcinoma. In 34 cases,33 of them were treated by surgical operation,17 patients with endometrial carcinoma and 19 with colorectal carcinoma received further adjuvant treatment of chemotherapy and (or) radiotherapy after operation, the median follow-up period was 49 months (range from 8 to 218 months),11 died due to tumor,22 survive and 1 lost, among the survivors,14 survive without tumor and 8 survive with tumor.2-year survival rate was 84.3% and 5-year survival rate was 63.1%.Conclusion:The age of diagnosed in patients with double primary carcinoma of endometrial carcinoma and colorectal carcinoma is earlier than that of sporadic ones; a part of the cases has a cancer family history and the survival is similar to that of sporadic colorectum carcinoma; Some patients with double primary carcinoma of endometrial carcinoma and colorectal carcinoma can be diagnosed with Lynch syndrome. |
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