A unique uterine cervical "teratocarcinosarcoma": a case report.

BACKGROUND: Teratocarcinosarcoma (TCS) is a rare aggressive tumor of the nasal cavity and paranasal sinuses and has both epithelial and two or more mesenchymal components. In other organs, 5 cases of ovarian tumors closely resembling TCS have been reported; however, there has been no published case of cervical TCS. Herein, we describe a unique case of cervical tumor that had carcinosarcomatous and teratomatous features, resembling a sinonasal TCS. CASE PRESENTATION: A 45-year-old woman presented to our hospital for evaluation of a cervical lesion. The gynecologist found a large polypoid mass, whose biopsy showed glandular components of probable germ cell origin based on the immunohistochemical features. The patient underwent total hysterectomy with bilateral salpingo-oophorectomy. The cervical polypoid mass was found to consist of both epithelial and mesenchymal tissues, including immature glandular structure resembling fetal enteric tubules, neuroepithelial cells, hyaline cartilage, and rhabdomyosarcoma cells. This tumor was diagnosed as TCS of the uterine cervix. Following the surgery, the patient received radiotherapy and has been free of disease for 13 months. CONCLUSION: This is the first case report of cervical TCS. The tumor is thought to be histogenetically less associated with HPV infection, and its teratomatous components with an absence of cytogenetic abnormalities (including isochromosome 12p (i(12p)) suggest a analogous histogenesis compared to pure mature or immature teratoma.

Coexistence of endometrial mesonephric-like adenocarcinoma and endometrioid carcinoma suggests a Müllerian duct lineage: a case report.

BACKGROUND: Endometrial mesonephric-like adenocarcinomas exhibit classical histologic features of mesonephric carcinoma; however, it remains unclear whether these tumors represent mesonephric (Wolffian) carcinoma or endometrioid (Müllerian) carcinomas that closely mimic mesonephric carcinoma. CASE PRESENTATION: A 32-year-old Japanese primigravida presented with atypical vaginal bleeding. An endometrial biopsy suggested low-grade endometrioid carcinoma, and she was administered medroxyprogesterone acetate. Her tumor recurred 6 years later, and she underwent hysterectomy, salpingo-oophorectomy, and omentectomy, at which point she was diagnosed with mesonephric-like adenocarcinoma of the uterine endometrium. Retrospective pathological review of the initial biopsy confirmed coexisting low-grade endometrioid carcinoma and mesonephric-like adenocarcinoma of the uterine endometrium. On immunohistochemistry, the endometrioid carcinoma component was diffuse positive for estrogen and progesterone receptors but negative for thyroid transcription factor 1. However, the mesonephric-like adenocarcinoma component exhibited a mixture of estrogen receptor- and thyroid transcription factor 1-positive cells within the same glands. CONCLUSIONS: We encountered a patient with coexisting endometrial mesonephric-like adenocarcinoma and low-grade endometrioid carcinoma, which was treated using medroxyprogesterone acetate therapy, resulting in recurrence of mesonephric-like adenocarcinoma alone. These clinicopathological findings support the prevailing notions that mesonephric-like adenocarcinoma is a Müllerian adenocarcinoma exhibiting mesonephric differentiation.

Molecular association of functioning stroma with carcinoma cells in the ovary: A preliminary study.

The cancer stroma serves an important role in tumour behaviours, including invasion, metastasis, and response to chemotherapy. The stroma of ovarian carcinoma is sometimes specialized, with luteinisation and/or hyperthecosis, and is designated as the 'functioning stroma' because it exerts endocrine function and produces sex steroid hormones. In the present study, 14 ovarian cancers with functioning stroma, comprising 7 endometrioid carcinomas and 7 clear cell carcinomas, were analysed to evaluate the molecular association of the functioning stroma with carcinoma cells. The median age of the patients was 67 years (range, 52-85 years); 13 patients were postmenopausal, and one was in perimenopause. Serum oestrogen values ranged from 10 to 129 ng/ml, with a median of 51 ng/ml. Sequence abnormalities in AT-rich interaction domain 1A (ARID1A), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PIK3CA), Kirsten rat sarcoma viral proto-oncogene (KRAS) and phosphatase and tensin homolog (PTEN) were examined in whole tumours. For cancers positive for sequence abnormalities, their localization in carcinoma cells and/or stromal cells was examined. A total of 8 mutations - ARID1A (L2155L), PIK3CA (H1047R), KRAS (Q12V, E31K, Q61L), and PTEN (C105fs*8) - were identified in the whole tumours of 5 patients. Seven of these eight mutations were detected only in carcinoma cells. However, one case of endometrioid carcinoma had a KRAS (E31K) mutation in both carcinoma and stromal cells. In conclusion, although functioning stromal cells of ovarian cancer are usually thought to be non-neoplastic, some may share an origin with carcinoma cells.

Impact of TP53 immunohistochemistry on the histological grading system for endometrial endometrioid carcinoma.

Endometrial endometrioid carcinoma is usually divided into three histological subgroups: grade 1 (G1), grade 2 (G2), and grade 3 (G3). Most cases of endometrial endometrioid carcinoma G1/2 have a favorable prognosis, although some can have unfavorable outcomes, especially when they involve elderly patients, with similarities to endometrioid carcinoma G3 and serous carcinoma. This retrospective study evaluated whether TP53 abnormalities in endometrial endometrioid carcinoma could be used to supplement the current grading system and improve its ability to predict clinical outcomes. Immunohistochemical expression of TP53 was analyzed using tissue microarrays from the surgically resected specimens of 475 patients with endometrial endometrioid carcinoma. Weak or moderate expression was defined as TP53-normal expression, while absent or strongly positive expression was defined as TP53-aberrant expression. The endometrial endometrioid carcinomas had originally been diagnosed as G1 (69%), G2 (18%), and G3 (13%). Univariate analyses revealed that TP53-aberrant expression was associated with poor survival in G1 and G2 cases, but not G3 cases. In addition, age (<60 years vs. ≥60 years) was correlated with TP53-aberrant expression in G1 cases (3% vs. 16%, p = 0.001), but not in G2 or G3 cases. Based on immunohistochemical TP53 expression, the endometrial endometrioid carcinomas were reclassified using a prognostic grading system as high-grade (G1 or G2 with TP53- aberrant expression, and G3 with TP53-normal or -aberrant expression) or low-grade (G1 or G2 with TP53-normal expression). The multivariate analyses revealed that the prognostic grading system (using histological grade and TP53 expression) could independently predict poor progression-free survival (hazard ratio: 2.91, p < 0.001) and overall survival (hazard ratio: 3.62, p < 0.001). Therefore, combining immunohistochemical TP53 expression with the traditional histological grading system for endometrial endometrioid carcinoma may help improve its ability to accurately predict the patient's prognosis.

A tolerance gene for prenylated flavonoid encodes a 26S proteasome regulatory subunit in Sophora flavescens.

Yeast functional screening with a Sophora flavescens cDNA library was performed to identify the genes involved in the tolerant mechanism to the self-producing prenylated flavonoid sophoraflavanone G (SFG). One cDNA, which conferred SFG tolerance, encoded a regulatory particle triple-A ATPase 2 (SfRPT2), a member of the 26S proteasome subunit. The yeast transformant of SfRPT2 showed reduced SFG accumulation in the cells.

Immortalized dendritic cell line with efficient cross-priming ability established from transgenic mice harboring the temperature-sensitive SV40 large T-antigen gene.

The uptake of an antigen and its presentation to specific T cells by dendritic cells (DCs) is a primary event in initiation of humoral and cellular immune responses as well as the induction of cytotoxic T cells (CTLs). DCs are induced by culturing bone marrow cells in the presence of GM-CSF. However, the resulting DCs are short-lived and the culture usually contains CD11c-negative non-DC cells, which adversely affects reproducibility and makes interpretation of the experimental results difficult. Therefore, it would be useful if DCs could be readily immortalized with their functions being retained. In this study we established a novel, immortalized murine DC line with antigen-presenting capacity in vitro as well as an augmenting effect on humoral and cellular immune responses in vivo, utilizing bone marrow cells from transgenic mice harboring the temperature-sensitive SV40 large T-antigen gene. In the presence of GM-CSF, the resulting DC line, termed SVDC, could be continuously subcultured for more than 12 months. When pulsed with OVA alone or OVA-IgG immune complexes via Fcgamma receptors, SVDC augmented OVA-specific T cell proliferation efficiently in vitro, and elicited OVA-specific IgG production in vivo on the adoptive transfer of pulsed SVDC into naive mice. Interestingly, SVDC exhibited significantly high cross-priming ability compared to DCs in a short-term culture, thus leading to their extremely high effectiveness in inducing anti-tumor immunity in vivo. Thus, SVDC is useful for the detailed characterization of antigen presentation, and for research on the various therapeutic benefits of DC vaccination to elicit specific immune responses in immunodeficiencies, infectious diseases and cancer.