Local lymphocytes and nitric oxide synthase in the uterine cervical stroma of patients with grade III cervical intraepithelial neoplasia

OBJECTIVES: Precancerous and cancerous cells can trigger an immune response that may limit tumor development and can be used as a prognostic marker. The aims of the present study were to quantify the presence of B and T lymphocytes, macrophages and cells expressing inducible nitric oxide synthase (iNOS) in the cervical stroma of women with grade III cervical intraepithelial neoplasia (CIN III) or in the intratumoral and peritumoral tissue of women with stage I invasive carcinoma. METHODS: Cervical tissue specimens were obtained from 60 women (20 each from control tissues, CIN III and invasive carcinomas). The average ages in the control, CIN III and invasive groups were 43.9 (± 4.3), 35.5 (± 9.5), and 50 (± 11.2) years, respectively. The specimens were immunohistochemically labeled with antibodies to identify T lymphocytes (CD3), cytotoxic lymphocytes (CD8), B lymphocytes (CD20), macrophages (CD68) and iNOS. We evaluated the markers in the stroma above the squamocolumnar junction (control), at the intraepithelial lesion (CIN cases), and in the nfiltrating tumor. Two independent observers performed the immunohistochemical analysis. RESULTS: T lymphocytes, B lymphocytes, macrophages and iNOS were present more frequently (P<0.05) in the stroma of peritumoral invasive tumors compared to the controls and intratumoral invasive cancer samples. CD3+ and CD20+ lymphocytes were present more frequently in CIN III patients compared to samples from patients with intratumoral invasive cancer (P<0.05). CONCLUSION: High numbers of T and B lymphocytes, macrophages and iNOS-expressing cells in the peritumoral stroma of the invasive tumors were observed. Cell migration appeared to be proportional to the progression of the lesion.

Management of Patients with CIN III and Positive Margins After Cervical Conization / 대한산부인과학회잡지

OBJECTIVE: To evaluate conservative management of patients with cervical intraepithelial lesion, grade III (CIN III) and positive resection margins after cervical conization. METHODS: We reviewed records of 64 patients undergoing cervical conization revealing CIN III with positive resection margins between January 1997 and December 1999. Thirty-three (51.5%) patients underwent conization only and thirty-one (48.5%) underwent conization and subsequent hysterectomy. These patients were followed up with a Pap smear every 3-6 months and then persistence and recurrence were determined in each group. The sites of incomplete excision and HPV infection at cone and residual lesion at hysterectomy specimen were evaluated. RESULTS: Thirty-one of 33 patients receiving conservative management and all 31 patients receiving subsequent hysterectomy had negative Pap smear (P=0.262). In the group of the conservative management, one case of 11 patients with extension to the endocervical margin had positive Pap smear (P=0.577). One of 17 cases with HPV infection and one of 10 cases with negative HPV testing had positive cytology (P=0.630). In the group of subsequent hysterectomy, nine cases (42.86%) of 21 patients with extension to endocervical margin and two (22.22%) of 9 patients with extension to exocervical margin had residual lesion in hysterectomy specimen (P=0.258). Only one (8.33%) of 12 cases with positive HPV and five (50%) of 10 patients with negative HPV had residual lesion (P=0.043). CONCLUSION: Patients with CIN III and positive resection margins after cervical conization can be followed appropriately with serial cytology. Endocervical margin involvement and HPV infection were not statistically significant predictors of residual lesion, persistence and recurrence in our patients.