Ex vivo expansion of CD56+ NK and NKT-like lymphocytes from peripheral blood mononuclear cells of patients with ovarian neoplasia.

Methods for ex vivo expansion of natural killer (NK) cells have allowed obtaining enough numbers of human NK cells for clinical trials. However, the evaluation of these methods has been mostly limited to haematological malignancies. This study aimed at evaluating a method for selective expansion of NK cells when applied in peripheral blood mononuclear cells (PBMC) of patients with ovarian neoplasia. PBMC from 13 volunteer patients with ovarian neoplasia, seven benign and six malignant tumours, were cultured in CellGro medium supplemented with anti-CD3 (9-10 initial days), IL-2 and foetal bovine serum for 21 days. The resulting effector cells were evaluated for their phenotype, cytotoxicity and cytokine secretion. PBMC cultures resulted in multiple populations (NK, NKT and T) of effector cells, enriched with CD56(+) lymphocytes. NK cells from patients with benign and malignant ovarian neoplasia were expanded 139.6 ± 63.4 and 82.7 ± 25.3-fold, respectively, being the largest lymphocyte subtype among CD56(+) population. Effector cells expanded from patients with malignant ovarian neoplasia had higher proportion of T lymphocytes and altered cytokine production patterns, characterized by lower INF-γ, TNF-α and higher IL-4, compared with patients with benign ovarian neoplasia. Effector cells were cytotoxic against K562 and OVCAR3 cell lines. Cytotoxicity was significantly higher (P < 0.05) using magnetically separated CD56(+) effector cell fractions compared with CD56-deprived ones. The present study demonstrates the feasibility of the culture system employed to generate effector cells, enriched with CD56(+) lymphocytes, from PBMC of patients with ovarian neoplasia. NK cells were the largest lymphocyte subtype among the CD56(+) population and the main variable among the final effector cell preparation affecting target cell killing.

Stromal cells play a role in cervical cancer progression mediated by MMP-2 protein.

Metalloproteinases, especially metalloproteinase-2 (MMP-2), are known for their role in the degradation of the extracellular matrix. Nevertheless, a thorough understanding of MMP-2 expression in neoplastic lesions of the uterine cervix has yet to be accomplished. This study aimed to analyze the MMP-2 expression in cervical intraepithelial neoplasia III (CIN3) and in cervical squamous cell carcinoma, in tumor cells and adjacent stromal cells. MMP-2 expression was assessed by an immunohistochemical technique. MMP-2 expression was greater in the stromal cells of invasive carcinomas than in CIN3 (p < 0.0001). MMP-2 expression in stromal cells correlates with the clinical stage, gradually increasing as the tumor progresses (p = 0.04). This study corroborates that stromal cells play an important role in tumor invasion and progression, mediated by the progressive enhancement of MMP-2 expression from CIN3 to advanced invasive tumor. The intense MMP-2 expression most probably is associated with poor tumor prognosis.

Correlation between histological criteria and human papillomavirus presence based on PCR assay in cervical biopsies.

UNLABELLED: The aim was to correlate histological findings in cervix lesions to human papillomavirus (HPV), as detected by polymerase chain reaction (PCR). One hundred and seven women with atypical Pap smear were submitted to colposcopic examination, and suspicious images were biopsied. The PCR assay was performed with the primers MY09/11 and GP05/06+ and, as control, the beta-globin gene was amplified. The morphological findings were correlated to HPV positivity: parakeratosis, acanthosis, koilocytotic atypia (KA), binucleation, dyskeratosis, and number of mitoses. From 107 patients, 61 biopsies were taken: 11 chronic cervicitis (CC), 36 cervical intraepithelial neoplasia (CIN) (13 CIN I; 10 CIN II; 13 CIN III), and 14 suggestive for HPV (SHPV). DNA extraction was not possible in eight cases. HPV was found in 35% CC, 77% CIN, and 64% SHPV. The analysis did not indicate any morphological criteria strongly related to HPV. The findings with highest sensitivity for HPV were KA (88.89%) and binucleation (75%), but with low specificity of 29.41 and 52.94%, respectively. The higher predictive positive values (PV+) for HPV were also KA (72.73%) and binucleation (77.14%). Considering KA, dyskeratosis and binucleation together, PV+ was 72.41%. CONCLUSION: Although indicative, none of the studied morphological criteria was always related to PCR virus detection, denoting some limitations for histological diagnosis.

Malignant mixed Mullerian tumor of the uterine cervix with neuroendocrine differentiation.

Malignant mixed Mullerian tumors (MMMTs) are rare neoplasms. We report the clinical, pathologic, and immunohistochemical features of an MMMT primary of uterine cervix. This lesion was composed of a poorly differentiated epithelial component (cytokeratin positive) and a spindle cell component (vimentin positive) with heterologous (myoblastic) differentiation (focal 1A4 positive). There were also cells with neuroendocrine features that expressed S-100 and chromogranin A. Along with a brief review of this amazing neoplasm, some histogenetic concepts relevant to this case are discussed. To our knowledge this is the first report of a malignant mixed Mullerian tumor of the uterine cervix with neuroendocrine differentiation.

Ovarian germ cell cancer: clinicopathologic analysis and outcome of 31 cases.

AIMS: The aim of the study was to evaluate some clinicopathologic characteristics and the outcome of patients with ovarian germ cell cancer (OGCC) treated with cisplatin-based chemotherapy. METHODS: It was a clinical retrospective study. The clinical charts of 31 patients with OGCC assisted at the Department of Obstetrics and Gynecology of the State University of Campinas, Brazil, from January 1986 to June 1997 were reviewed. RESULTS: Ten patients had dysgerminoma and 21 patients nondysgerminomatous tumors. Women with dysgerminoma and nondysgerminomatous tumors did not present differences regarding surgical staging, age, ascites or residual tumor after the initial surgery. Frozen section, performed in 16 patients, showed some discrepancy with paraffin histology diagnosis in 8 patients. Platinum-based chemotherapy was used in 5/10 patients with dysgerminoma and in 17/21 patients with nondysgerminomatous tumors, with a 5-year survival of 100% for the dysgerminoma and 53% for the nondysgerminomatous group. CONCLUSIONS: Women with dysgerminoma and nondysgerminomatous tumors did not present differences regarding clinicopathologic characteristics. The prognosis for patients with dysgerminoma was better than for those with nondysgerminomatous tumors. Frozen section had a high error rate in diagnosing OGCC intraoperatively.