Clinical Significance Of Micrometastasis Detection In Lymph Nodes Of Patients With Early-stage Cervical Cancer

ObjectiveLymph nodes status is a major determinant of diseases recurrence after patients undergo extensive abdominal hysterectomy and bilateral pelvic lymphadenectomy for cervical cancer. A proportion of patients without lymph node metastasis developed recurrence, suggesting the presence of occult micrometastasis. The purpose of this study is to assess the feasibility of HPV16/18, the specific marker of cervical cancer, and telomerase, the specific marker of tumor, detection of lymph node micrometastasis from cervical cancer and to determine their clinical significance.MethodsPrimary tumors and lymph nodes which were conventional pathological diagnosis show negative metastasis, dissected from sixty-one patients who have been performed extensive abdominal hysterectomy and bilateral pelvic lymphadenectomy with the early cervical cancer between 2005 and 2007 in Department of Obstetrics and Gynecology, Anhui Provincial Hospital. The positive and negative control groups are lymph nodes which were conventional pathological diagnosis show metastasis dissected from 13 cases of patients with the early cervical cancer and from 15 cases of patients with the benign gastrohelcoma, respectively. All specimens were re-examined copies of HPV16/18 using FQ-PCR and telomerase using PCR-ELISA, respectively. And we used immunohistochemical staining using monoclonal antibody cytokeratin 19 as the standard of lymph node micrometastasis to evaluate the clinical significance of combination of detecting HPV16/18 using FQ-PCR and telomerase using PCR-ELISA in negative pathological lymph nodes.Results1. By immunohistochemical staining using monoclonal antibody cytokeratin 19, lymph nodes micrometastases were observed in 11 of 61 patients, of which, 9 cases of HPV16/18-DNA positive and 10 cases of telomerase positive, respectively.2. When combination of detecting HPV16/18 using FQ-PCR and telomerase using PCR-ELISA, lymph nodes micrometastases were observed in 17 of 61 patients, of which, HPV16/18-DNA and telomerase were all positive in 12 cases, and in the remaining 5 cases only HPV16/18-DNA or telomerase were positive. In 13 cases of lymph nodes which were conventional pathological diagnosis show metastasis dissected from patients with the early cervical cancer, HPV16/18 and telomerase were all positive, however, in 15 cases of lymph nodes from patients with the benign gastrohelcoma, none was detected the two molecules. Positive rate of micrometastasis of combination of detecting HPV16/18 using FQ-PCR and telomerase using PCR-ELISA is higher than that of detecting CK19 using immunohistochemistry(χ2=4.17, p<0.05). And there is direct correlation of telomerase and HPV16/18-DNA in lymph nodes of cervical cancer(r=0.61,p <0.01).3. Copies of HPV16/18-DNA in lymph nodes metastasis pathologically are higher than in lymph nodes detected positive micrometastasis (104.79±0.62 vs 103.38±0.78), while less than in primary tumor (106.65±0.79) (p <0.01).4. Telomerase activity in lymph nodes metastasis pathologically are higher than in lymph nodes nonmetastasis detected positive micrometastasis (0.31±0.08 vs 0.43±0.15), while less than in primary tumor (0.74±0.29) (p <0.05; p <0.01).5. When compared with immunohistochemical staining using monoclonal antibody cytokeratin 19 which was used for detecting lymph node micrometastasis, we obtained the result that the sensitivity and negative predictive value of combination of detecting HPV16/18 using FQ-PCR and telomerase using PCR-ELISA is higher than that of only one.6. The incidence of micrometastasis was correlated with clinical stage, primary tumor size, invasion of myometrium and parametrium, but no correlated with year, tumor cell type and histological differentiation (p <0.05).ConclusionOur study suggested that the detection of HPV16/18 using FQ-PCR and telomerase using PCR-ELISA are capable of identifying micrometastases in lymph nodes missed by routine hematoxylin and eosin (HE) staining with cervical cancer, and combination of detecting the two molecules is more available. Microetastases detection in negative lymph node of cervical cancer may be recommended to direct adjuvant therapy after operative and predict prognosis.