Part â… :Preliminary Study Of Serum MicroRNAs Related To The Sensitivity To Concurrent Chemoradiotherapy In Advanced Cervical Squamous Cell Carcinoma Part â…¡:Clinical Analysis Of 32 Cases With Neuroendocrine Carcinoma Of The Uterine Cervix In Early-Stage

Part IPreliminary study of serum microRNAs related to the sensitivity to concurrent chemoradiotherapy in advanced cervical squamous cell carcinoma[Background and Objectives] Cervical carcinoma is one of the most common female malignancies worldwide. In China, a developing country, cervical carcinoma occupies the first place of three female reproductive malignancies. Based on some strong evidence, concurrent chemoradiotherapy (CCRT) was estsblished as the standard treatment for patients with advanced cervical carcinoma, instead of previous simple radiotherapy. In clinical practice, we found that patients had similar clinic-pathological factors may response differently to CCRT. Obviously the intrinsic sensitivity of tumor plays a key role. MicroRNA (miRNA) is a class of non-coding small single-stranded RNA, involved in the initiation and development of different tumors, and its role in sensitivity to chemoradiotherapy draws more and more attention. Our previous studies are based on cervical cancer tissues. MicroRNA microarray analysis showed that 170 microRNAs expressed significantly differently in tumor tissue of cervical carcinoma between radioresistant group and radiosensitive group. Combined with the prediction analysis of target gene and literature review, six microRNAs were chosen to be the targets for distinction of radioresistant group and radiosensitive group. The six microRNAs were miR-101, miR-125a-5p, miR-365, miR-886-3p, miR-1285 and miR-492, of which, the former four were upregulated in radioresistant group, and the other two were downregulated. Hierarchical cluster analysis showed that the six microRNAs can well separate radioresistant group and radiosensitive group. In recent years, the theory of circulating microRNA has been developing rapidly. Blood specimens are easy to obtain and convenience to clinical application. This study aims at identify serum microRNAs are related to CCRT sensitivity, and lay the foundation for further study of serum tumor makers for CCRT sensitivity and potential targets for therapy.[Materials and Methods] Cervical squamous cell carcinoma patients in FIGO stage Ⅱb-Ⅳa treated with CCRT between January,2014 and April,2014 in Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences. The serum samples of the patients were collected before treatment. Based on the sensitivity differences to CCRT, sensitive and resistant groups were separated, and each group has ten patients with well-balanced clinical-pathologic features. Total microRNAs were extracted, and TaqMan Real-time PCR microRNA Array was used to identify differentially expressed microRNAs correlated with CCRT sensitivity between the two groups. RQ manager 1.2 and Data Asist V2.0 software was used to analyse the chip. Then quantitative polymerase chain reaction was used to verify the expression defferentions of microRNAs selected in the microRNA Array in a larger sample size(17 cases from sensitive group, and 22 cases from resistant group).[Results] MicroRNA chips expression analysis showed that three microRNAs expressed differentially significantly (fold change>2, and P<0.05) between the two groups. They are miR-136 (downregulated in resistant group), miR-152 (upregulated in resistant group) and miR-206 (upregulated in resistant group). Verified results in a larger sample size showed that miR-136 (downregulated in resistant group) and miR-206 (upregulated in resistant group) were obviously different between the two groups. The difference was statistically significant (P<0.05)[Conclusion] Serum miR-136 and miR-206 might be associated with CCRT sensitivity. The lower expression of miR-136 and higher expression of miR-206 in serum might indicate CCRT resistance in cervical cancer.Part IIClinical analysis of 32 cases with neuroendocrine carcinoma of the uterine cervix in early-stage disease[Objective] To investigate the survival and recurrence data after treatment in neuroendocrine carcinoma of the uterine cervix(NECUC) with stage Ⅰb～Ⅱa, and to analyse its prognostic factors.[Methods] Thirty-two cases of primary NECUC in early-stage disease treated from Jan.2005 to Dec.2013 at Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences were reviewed, and their data of clinicopathologic characteristics were collected and analysed. The median age was 37 years(range,23-57 years). The distribution by International Federation of Gynecology and Obstetrics (FIGO) clinical stage:19 stage Ⅰ b1,10 stage Ⅰ b2,1 stage Ⅱa1,2 stage Ⅱa2.Pathologic types: 22 cases of small cell carcinoma,1 case of atypical carcinoid,9 cases of mixed carcinoma. The diameter of cervical tumor:12 cases≥4 cm,20 cases< 4cm. All patients underwent radical hysterectomy and pelvic±para-aortic lymphadenectomy, and 15 cases of them were preserved unilateral or bilateral ovaries. Pathologic examination showed that 25 cases with cervical deep stromal thickness≥1/2,21 cases with lymph-vascular space invasion (LVSI), and 18 cases with pelvic and (or) para-aortic lymph nodes involvement. Ten cases were performed neoadjuvant chemotherapy (range,1～3 cycles), all patients received postoperative chemotherapy (range,3～6 cycles),and 15 patients were treated with radiotherapy after surgery. The follow-up data were updated on Jul.2014. The median follow-up time was 18 months (range,7～71 months). A retrospective analysis was conducted to analyse the survival and recurrence data, and to explore the prognostic factors of NECUC.[Results] Thirteen patients died during the follow-up period. The cumulative progression-free survival (PFS) of 2 and 5 years were 54.2% and 38.1%, and the estimated median PFS was 29 months. The cumulative overall survival (OS) of 2 and 5 years were 56.1% and 44.9%, and the estimated median OS was 31 months. Fourteen cases had recurrence, and the median recurrence time was 9 months (range,3-30 months). Recurrent or metastatic sites:2 cases in pelvis,4 cases in liver,3 cases in lung, 3 cases in adrenal glands,3 cases in bones,2 cases in brain,1 case in pancreas,1 case in lymph nodes of para-aorta and neck, and 3 cases had metastasis in two or more organs. Thirteen cases with recurrence died of disease, and another one is alive with disease. The univariate analysis showed that lesion size of the cervix and FIGO stage are significant prognostic factors (P<0.01), while age, tumor components, deep invasion in cervical stromal, LVSI, pelvic and (or) para-aortic lymph nodes involvement, neoadjuvant chemotherapy, adjuvant radiotherapy and preserving ovaries were not significantly associated with prognosis (all P>0.05).[Conclusions] The prognosis of NECUC in early-stage is poor and the lesion size of the cervix and FIGO stage are prognostic factors.