Optimal sampling devices for liquid-based procedure in screening for cervical cancer: comparison between cotton stick/Cytobrush and Cervex-Brush.

OBJECTIVE: To find an appropriate sampling device for a liquid-based procedure in the population screening for cervical cancer, focusing on bleeding at sampling and the amount of cells smeared. METHODS AND MATERIALS: 1,000 consecutive women who underwent primary screening were studied. The specimens were obtained with the cotton stick/Cytobrush® method in the first 500 cases or with the Cervex-Brush® in the following 500 subjects, and were processed using the Thinlayer Advanced Cytology Assay System (TACAS™) following the manufacturer's instructions. RESULTS: (1) Bleeding at cellular sampling using the cotton stick/Cytobrush and Cervex-Brush methods occurred in 1.2 and 8.8% of the cases, respectively (p < 0.0001). (2) The incidences of cells obtained with the two methods which covered the whole area, <1/2 and ≥1/4, and <1/4 of the observation fields were 55.4 versus 62.2% (p < 0.05), 14.6 versus 9.4% (p < 0.05), and 2.0 versus 4.0% (p < 0.05), respectively. (3) The incidences of endocervical or metaplastic cells obtained with ≥500 and <10 were 34.6 versus 20.0% (p < 0.01) and 9.4 versus 18.4% (p < 0.01), respectively. In cases of cells covering <1/4, incidences with <10 were 0 and 0.6% (n = 3), respectively. (4) Detection rates of abnormal cytology were 3.4 and 5.2% (n.s.), including atypical squamous cells of undetermined significance in 2.4 and 3.2%. CONCLUSIONS: The cotton stick/Cytobrush is superior to the Cervex-Brush as a cellular sampling device for the TACAS liquid-based procedure.

Liquid-based preparation for endometrial cytology--usefulness for predicting the prognosis of endometrial carcinoma preoperatively.

BACKGROUND: The authors evaluated the applicability and usefulness of immunocytochemical staining for cyclin A, p53, estrogen receptor alpha (ER-alpha), and progesterone receptor B (PR-B) as a preoperative prognostic indicators for endometrial carcinoma using endometrial cytology with the liquid-based cytology (LBC) method. METHODS: Cytologic specimens from 44 patients who had endometrial carcinoma were prepared with the LBC method. The results of immunocytochemical and immunohistochemical staining for cyclin A, p53, ER-alpha, and PR-B were compared with clinicopathologic parameters and prognosis. RESULTS: Patients who had positive results for cyclin A and p53 and negative results for ER-alpha and PR-B appeared to have unfavorable clinicopathologic characteristics, such as high-grade histology, advanced clinical stage, lymphovascular space involvement (LVSI), and deeper myometrial invasion (MI), and had a poor prognosis. In contrast, patients who had positive results for ER-alpha and PR-B, and negative results for cyclin A and p53 had favorable characteristics, such well differentiated tumor, early clinical stage, negative LVSI, and less MI, and had a good prognosis. Immunostaining results from cytologic specimens obtained in the clinic and at surgery and from histologic specimens obtained at surgery were correlated positively. CONCLUSIONS: Consistent specimens that were prepared using the LBC method facilitated multiple immunocytochemical analyses. Endometrial cytology with the LBC method was useful for predicting the prognosis of patients with endometrial carcinoma before therapy.

Significance of matrix metalloproteinase-7 [correction of matrix metalloproteinase-2], -11 and tissue inhibitor of metalloproteinase-1 expression in normal, hyperplastic and neoplastic endometrium.

BACKGROUND: Matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) are key factors in the degradation of extracellular matrix and basement membranes. This study aimed to examine the expressions of MMP-7 and -11 and TIMP-1 in normal, hyperplastic and neoplastic endometrium and their correlation to clinicopathologic factors. PATIENTS AND METHODS: Tissue samples of 40 normal endometria, 20 endometrial hyperplasias and 120 endometrial endometrioid adenocarcinomas were used for the study. Immunohistochemical staining for MMP-7 and -11 and TIMP-1 protein was performed on formalin-fixed and paraffin-embedded tissue samples. These expressions were represented as incidence of expression. RESULTS: MMP-7 was highly expressed in the glands of the basal and functional layers during the proliferative and menstrual phases. MMP-11 expression in the gland of the basal layer and the stroma of the functional layer fluctuated during the menstrual cycle. TIMP-1 was highly expressed in the late secretory and menstrual phases. MMP-7 was expressed at significantly higher levels in endometrial hyperplasia than normal endometrium, whereas MMP-11 was expressed at lower levels. In endometrial adenocarcinoma, MMP-7, MMP-11 and TIMP-1 were expressed at the same levels as in hyperplasia. MMP-7 expression in endometrial carcinoma was correlated with myometrial invasion and estrogen receptor expression. The expression of MMP-7 in the adjacent stroma was associated with a poor prognosis. CONCLUSION: MMP-7, MMP-11 and TIMP-1 expression may be regulated by the menstrual cycle, and related to the degradation and remodeling of the normal endometrium. MMP-7 expression might be a prognostic factor in endometrial carcinoma.

Phase II study of radiation therapy combined with weekly nedaplatin in locally advanced uterine cervical carcinoma: Kitasato Gynecologic Radiation Oncology Group (KGROG 0501).

In order to evaluate the safety and efficacy of chemoradiotherapy using nedaplatin for locally advanced uterine cervical carcinoma in Japanese patients, we have started a single-institute phase II trial. Eligibility criteria include: (i) pathologically proven squamous cell carcinoma or adenocarcinoma, (ii) clinical FIGO stage Ib, IIa, or IIb with bulky tumor (> 40 mm) or pelvic lymph node swelling, or (iii) clinical FIGO stage IIIa, IIIb and IVa, (iv) no para-aortic lymph node swelling. A combination of external beam radiation and high dose rate intracavitary irradiation is given. Nedaplatin (30 mg/m2) is intravenously infused on a weekly basis for five times. The primary endpoint is 3-year overall survival, and the secondary endpoints are tumor response, 2-year overall survival, 3-year progression-free survival, acute adverse events, protocol treatment compliance, and late adverse events. We plan to recruit 45 patients within 3 years.

High expression of skp2 correlates with poor prognosis in endometrial endometrioid adenocarcinoma.

PURPOSE: Skp2 interacts with the degradation of cyclin-dependent kinase inhibitor p27. This study aimed to investigate the correlation of skp2 expression with the expression of p27 and other cell cycle regulators, and clinicopathological parameters in endometrial endometrioid adenocarcinoma. METHODS: Tissue samples of 136 endometrioid adenocarcinomas, in addition to 20 endometrial hyperplasias and 20 normal endometria, were immunohistochemically stained for skp2. The expression was represented as a labeling index (LI), which indicates the percentage of positive nuclei. RESULTS: Skp2 staining was localized in the nuclei of the glandular cells of the proliferative phase endometrium, and endometrial hyperplasia and carcinoma cells. Skp2 expression was increased significantly in those of higher histological grade. The high level of skp2 expression was significantly correlated with the presence of lymph node metastasis and lymph-vascular space involvement. The LI of skp2 in endometrial carcinoma was significantly correlated with that of p27, Ki-67, cdk2, cyclin A, cyclin D1, cyclin E, p53 and PTEN. The high level of skp2 expression (LI> or =20%) was significantly correlated with the patients' poor survival. CONCLUSIONS: The skp2 level might have increased due to p27 accumulation and may be a good indicator of proliferative activity and poor prognosis.

Aspiration cytology of malignant fibrous histiocytoma after radiation therapy for carcinoma of the uterine cervix: a case report.

BACKGROUND: Cytologic reports on malignant fibrous histiocytoma (MFH) following radiation therapy for carcinoma of the uterine cervix are very rare. CASE: A 59-year-old woman presented with slowly increasing pain in the left hip joint. Eight years earlier, she had received radiotherapy at a dosage of 5,000 cGy to the whole pelvis for carcinoma of the uterine cervix. An osteolytic lesion of the pelvic bone was revealed on computed tomography, and a hard tumor was palpable in the left pelvic cavity. Fine needle aspiration (FNA) of the tumor via the left vaginal wall obtained 0.5 mL of yellow fluid consisting of markedly anaplastic and pleomorphic giant cells. Frequent multinucleation and mitoses were observed, although no atypical spindle cells were observed. Immunocytochemistry disclosed vimentin reactivity. An open biopsy of the tumor revealed the histologic and immunohistochemical features of MFH arising in the pelvic cavity. CONCLUSION: FNA of the pelvic lesion via the vaginal wall revealed an MFH in the radiation therapy field. This is one of the few reports dealing with FNA cytology of a postradiation sarcoma in the pelvic cavity.

Significance of progesterone receptor-A and -B expressions in endometrial adenocarcinoma.

The progesterone receptor (PR) has two isoforms, A and B, among which PR-B is mainly involved in regulating proliferation of the uterine endometrium. In this study, immunohistochemical analysis was carried out to investigate the correlation of PR-A and -B expressions with cell cycle-regulatory proteins and clinicopathological parameters in endometrial adenocarcinoma. One hundred and forty-one endometrioid adenocarcinomas [76 with well-differentiated (G1), 35 with moderately differentiated (G2) and 30 with poorly differentiated (G3)] were used. Specimens of formalin-fixed and paraffin-embedded tissue were immunohistochemically stained using the high polymer method (HISTOFINE, NICHIREI). The percentage of positive nuclei of tumor cells observed in three high power fields was expressed as a labeling index (LI). PR-B expression significantly occurred more frequently in G1. It was inversely correlated with p53 gene mutation and p53 over expression, and also with clinicopathological variables, including myometrial and lymph-vascular space invasion and the FIGO stage. Patients with negative PR-B had a poorer prognosis than positive cases. PR-A expression was also significantly higher in G1 and was inversely correlated with Ki-67 expression and myometrial invasion, but not with prognosis. PR-A and -B expressions were significantly correlated with biologically malignant potential. Especially, PR-B expression is useful as a prognostic indicator of endometrial adenocarcinoma.