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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report the pathological findings of a woman with a sub-acute cerebellar syndrome who had undergone surgery 3 years before for endometrial carcinoma. Both serum and cerebrospinal fluid contained high titres of autoantibodies against the cytoplasm of Purkinje cells that recognized a band of 62 kDa on immunoblotting of neuronal extracted proteins (pattern anti-Yo). No tumour was found despite a full range of gynaecological investigations; the neoplastic marker CA125 was slightly elevated and oligoclonal bands were detected in the cerebrospinal fluid. The patient died from acute myocardial infarction 4 months after developing this syndrome. At autopsy, no macroscopic evidence of tumour was obtained and the brain showed no abnormalities. On microscopic examination of the central nervous system diffuse degeneration of Purkinje cells could be seen throughout the cerebellum. Immunohistochemical analysis showed a CD8 lymphocyte infiltration in the cerebellum and cerebral cortex and diffuse microglial activation throughout the brain. These cells expressed high levels of MHC-II antigens on their cell membranes. The serum autoantibodies reacted with the cytoplasm of the remaining Purkinje cells. The short interval between the onset of symptoms and death of the patient could explain the difference between our findings and those reported in the literature in which no inflammatory infiltrates were detected. The immunohistochemical findings as well as the inflammatory cerebrospinal fluid profile seen in our case seem to support the concept that in paraneoplastic cerebellar degeneration with anti-Yo antibodies, an immune mediated mechanism is responsible for the damage to the cerebellum.
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PMID:Sub-acute cerebellar degeneration with anti-Yo autoantibodies: immunohistochemical analysis of the immune reaction in the central nervous system. 946 Jul 12

Uterine serous papillary carcinoma is a highly aggressive variant of endometrial cancer histologically similar to high grade ovarian cancer. Unlike ovarian cancer, however, it is a chemoresistant disease from onset, with responses to combined cisplatinum-based chemotherapy in the order of 20% and an extremely poor prognosis. In this study, we demonstrate that tumour lysate-pulsed autologous dendritic cells can elicit a specific CD8(+) cytotoxic T lymphocyte response against autologous tumour target cells in three patients with uterine serous papillary cancer. CTL from patients 1 and 2 expressed strong cytolytic activity against autologous tumour cells, did not lyse autologous lymphoblasts or autologous EBV-transformed cell lines, and were variably cytotoxic against the NK-sensitive cell line K-562. Patient 3 CD8(+) T cells expressed a modest but reproducible cytotoxicity against autologous tumour cells only at the time of the first priming. Further priming attempts with PBL collected from patient 3 after tumour progression in the lumboaortic lymph nodes were unsuccessful. Cytotoxicity against autologous tumour cells could be significantly inhibited by anti-HLA class I (W6/32) and anti-LFA-1 MAbs. Highly cytotoxic CD8(+) T cells from patients 1 and 2 showed a heterogeneous CD56 expression while CD56 was not expressed by non-cytotoxic CD8(+) T cells from patient 3. Using two colour flow cytometric analysis of intracellular cytokine expression at the single cell level, a striking dominance of IFN-gamma expressors was detectable in CTL populations of patients 1 and 2 while in patient 3 a dominant population of CD8(+) T cells expressing IL-4 and IL-10 was consistently detected. Taken together, these data demonstrate that tumour lysate-pulsed DC can be an effective tool in inducing uterine serous papillary cancer-specific CD8(+) CTL able to kill autologous tumour cells in vitro. However, high levels of tumour specific tolerance in some patients may impose a significant barrier to therapeutic vaccination. These results may have important implications for the treatment in the adjuvant setting of uterine serous papillary cancer patients with active or adoptive immunotherapy.
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PMID:Induction of tumour-specific CD8(+) cytotoxic T lymphocytes by tumour lysate-pulsed autologous dendritic cells in patients with uterine serous papillary cancer. 1185 27

Metachronous primary malignant tumors of uterine papillary serous carcinoma (UPSC) and non-Hodgkin's lymphoma (NHL) are rare. UPSC is a clinically aggressive and morphologically distinctive variant of endometrial carcinoma. We describe the clinical features of a 63-year-old patient with UPSC that was found 2 years after chemotherapy for malignant lymphoma of neck, stage IV and 5 months after radiation therapy for recurrence. This patient had undergone staging surgery and postoperative radiation for UPSC. One month after completion of radiotherapy, the patient expired due to persistence of the disease. The association between host immunity and UPSC is rarely described in the literature. Immunological profiles of this patient, with compositional changes of natural killer, B, and T cell, dramatically altered the percentage of CD4(+) T cell, CD8(+) T cell, and CD4/CD8 ratio, signifying depressed host immunity. Immunological profile of this patient stressed the issue of depressed host immunity and associated malignancies.
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PMID:Depressed host immunity in a case of metachronous primary uterine papillary serous carcinoma and non-Hodgkin's lymphoma. 1536 Dec 20

Although there are several hypotheses explaining the mechanisms of immune-privileged status of malignant tumor, the exact pathway has yet to be explored. Cyclooxygenase (COX)-2 plays a vital role in prognosis of cancer patients in terms of contribution to neoangiogenesis and apoptosis inhibition; however, the impact of COX-2 in immunomodulation has not been reported. We have evaluated the expression of COX-2 and its impact on infiltration of immune-competent cells into the tumor cell nest in endometrial carcinoma. Tissue specimens from 70 endometrial carcinoma patients who had undergone a curative resection were evaluated for COX-2 expression and host immune status (CD8+ T cells). COX-2 expression was associated with FIGO stage and myometrial invasion, but there was no statistically significant impact. CD8+ T cells within cancer cell nest (Nest CD8) were inversely correlated with the expression level of COX-2 (p = 0.0006). Nest CD8 became an independent predictor of patient survival (Hazard ratio = 10.300, p = 0.0304) in Cox's multivariate analysis. The expression level of COX-2 was found to be a significant predictor of disease relapse in univariate analysis (p = 0.0294) but not in multivariate analysis (p = 0.5949). In conclusion, increased nest CD8 produced a survival advantage in endometrial carcinoma patients. Moreover, tumor-produced COX-2, which reduces the infiltration of CD8+ T cells into cancer cell nests, may allow tumors to avoid immune surveillance.
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PMID:Role of cyclooxygenase-2 in immunomodulation and prognosis of endometrial carcinoma. 1560

Microsatellite instability (MSI) is seen in many cancers and is the result of either a germline or somatic defect in the DNA mismatch repair system. Microsatellite instability is common in endometrial cancers occurring in about 25% of cases with endometrioid histology. Tumor infiltrating lymphocytes (TIL) are more prominent in colorectal cancer cases with MSI. The presence of increased TIL is associated with increased survival in these colorectal cancers, and is suggested as one possible mechanism to explain the increased survival rates in colorectal cancer patients with MSI positive cancers. Some degree of evidence indicates that increased TIL is also predictive of increased survival in endometrial cancer. The relative levels and states of activation of TIL in endometrial cancers with and without MSI has not been explored. Our previous data indicates that global gene expression patterns from MSI and non-MSI endometrial cancers are distinct, however TIL markers were not over-represented on statistically relevant gene lists that distinguish these groups. We further examined these pre-existing microarray data by directly querying transcripts present in the T-cell gene ontology (GO) group. No significant differences were observed between MSI and microsatellite stable (MSS) groups. Finally we directly examined a set of T-cell marker transcripts previously utilized to define increased activated and cytotoxic TIL in MSI positive colorectal cancers. Whereas colorectal cancers with MSI have been previously demonstrated to contain higher ratios of CD8/CD3 message levels we observed no difference in endometrial cancers. In addition, levels of CD3 indicated no increases in TIL in MSI positive cases and 2 markers of activation, granzyme B and IL-2R were not different in MSI positive and negative cancers. These data indicate that significant differences in TIL derived transcripts do not occur between endometrioid endometrial cancers with and without microsatellite instability.
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PMID:Gene expression analysis of tumor infiltrating lymphocyte markers in endometrial cancers indicates no significant increases in those cases with microsatellite instability. 1719 60

This objective of this study was to investigate the expression of chemokine receptors in tumor cells and leukocytes in breast carcinoma effusions. The expression of leukocyte markers (CD3/4/8/14/16/19) and chemokine receptors (CXCR1/4, CCR2/5/7) was studied in 21 breast carcinoma effusions using flow cytometry. Breast carcinoma cells expressed CXCR4 in 7/21 (33%) effusions, with less frequent expression of CXCR1, CCR5, and CCR7. CXCR2 and CCR2 were absent. Lymphocytes showed frequent CXCR4, CCR5, and CCR7 expression, while CXCR1, CXCR2, CCR2 were rarely or never detected. Macrophages expressed all six receptors except for CXCR2. Comparative analysis of breast carcinoma effusions with previously studied ovarian and cervical/endometrial adenocarcinomas (ACs) showed significantly higher CXCR4 expression in breast carcinoma cells compared to the other gynecological ACs (p = 0.001). Breast and cervical/endometrial carcinoma effusions showed different expression of chemokine receptors in lymphocytes (lower CXCR1, higher CXCR4 and CCR7 levels; p = 0.012, p = 0.005, p < 0.001, respectively) and macrophages (higher CCR7 levels; p < 0.001), as well as lower CD8 counts (p < 0.001) and higher CD19 counts (p = 0.001) compared to ovarian carcinoma effusions. Higher numbers of CD8-positive lymphocytes (p = 0.080) and higher CCR7 monocyte expression (p = 0.087) were associated with a trend for shorter disease-free survival. In conclusion, breast carcinoma cells express CXCR4, a unique feature among metastatic ACs in effusions, with rare expression of other chemokine receptors. Chemokine receptor expression in leukocytes and lymphocyte counts significantly differ from those of ovarian carcinoma effusions. The prognostic role of CCR7 expression in monocytes and CD8 counts in breast carcinoma effusions merits further research.
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PMID:The chemokine receptor CXCR4 is more frequently expressed in breast compared to other metastatic adenocarcinomas in effusions. 1865 45

Progestins are used to treat complex atypical hyperplasia and well-differentiated endometrial carcinoma in women who desire fertility preservation and those who are poor surgical candidates. Although sensitivity to progestins is thought to be associated with the presence of estrogen and progesterone receptors, it is known that receptor-negative tumors can also respond to the agent, suggesting that there is another direct antitumor action of progestin. Because tumor immune response is an additional predictor of survival in well-differentiated endometrial carcinoma, it is surprising that the role of progestins in tumor immunity has not been investigated. Regulatory T cells modulate the immune response, whereas cytotoxic T cells directly target tumor cells. In this study, we investigated the effect of progestins on regulatory T cells and cytotoxic T cells. The pre- and posttreatment endometrial samples of 15 progestin-treated patients with complex atypical hyperplasia or well-differentiated endometrial carcinoma were evaluated for therapeutic response and the presence of cytotoxic T cells and regulatory T cells. Immunohistochemical analysis was performed for FOXP3 to identify regulatory T cells and for granzyme B to identify activated cytotoxic T cells. To further characterize the cytotoxic T cell's subpopulations, we performed CD8 (cytotoxic T-cell marker) and CD56 (natural killer cells marker). Ten of 15 patients had normal morphology on follow-up endometrial samplings, and 4 patients had persistence or progression of the disease. Regulatory T-cell counts pretreatment were significantly higher in complex atypical hyperplasia and well-differentiated endometrial carcinoma than in posttreatment normal endometrium. Residual complex atypical hyperplasia and well-differentiated endometrial carcinoma present in posttreatment samples maintained high regulatory T cells and low number of cytotoxic T cells. Progestin treatment was associated with striking increase in cytotoxic T cells in areas with decidual reaction. Before treatment, most of the granzyme B+ cytotoxic T cells in complex atypical hyperplasia and well-differentiated endometrial carcinoma were CD8(+) T cells, whereas after treatment, up to 80% of cytotoxic T cells were natural killer cells. These results suggest that progestin treatment affects subpopulations of lymphocytes in the endometrium and may induce immune suppression of complex atypical hyperplasia and well-differentiated endometrial carcinoma.
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PMID:Increased natural killer cells and decreased regulatory T cells are seen in complex atypical endometrial hyperplasia and well-differentiated carcinoma treated with progestins. 1973 83

In this study, we correlated the number of tryptase-reactive mast cells with the number of CD8-positive T cells in human endometrial adenocarcinoma biopsy specimens by means of immunohistochemical techniques. Results have shown that CD8-positive T cell counts correlate to tryptase-positive mast cell counts and that these parameters increase in accordance with the tumor progression of human endometrial carcinoma. These data suggest that inhibition of inflammation or manipulation of inflammatory resolution pathways may be a new therapeutic approach for the treatment of endometrial adenocarcinoma.
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PMID:Tryptase-positive mast cells and CD8-positive T cells in human endometrial cancer. 2170 49

This report describes the clinicopathologic features of a primary lymphoepithelioma-like carcinoma of the endometrium, representing only the fourth reported case of this tumor at this location. In addition to its classic morphologic features, focal clear cells were also identified within the tumor, thereby expanding the morphologic spectrum of the neoplasm at this location. A comprehensive immunohistochemical characterization of the tumor was performed, as was microsatellite instability testing. The tumor was diagnosed in a 79-year-old woman and was surgically/pathologically staged as IB by the International Federation of Gynecology and Obstetrics (FIGO) criteria. The tumor displayed typical morphologic features (tumor cells with a syncytial appearance in an inflammatory background) with the exception of the aforementioned polygonal cells with well-defined cell membranes and cytoplasmic clarity in <1% of the tumor. The epithelial component showed strong and diffuse immunoreactivity for CAM 5.2, p53, p16, E-cadherin, cytokeratin (CK) 7, vimentin, CKAE1/3, and epithelial membrane antigen. The MIB-1 proliferative index in these regions was about 70%. Approximately 10% to 30% of lesional cells showed strong immunoreactivity for CK903, S100, MOC31, CD138, but the pattern of positivity was patchy and discontinuous. The epithelial cells were entirely negative for CK5/6, smooth muscle actin, p504S, CK20, synaptophysin, chromogranin, CD56, CD99, WT-1, thyroid transcription factor-1, p63, CD117 (c-kit), CD34, calretinin, desmin, estrogen receptor, progesterone receptor, FLI-1, ALK-1, D2-40, cytomegalovirus antigen, Epstein-Barr virus-encoded RNA-1, Epstein-Barr virus, monoclonal carcinoembryonic antigen, and HER2/neu. The foci with clear cells were not immunophenotypically distinct from the non-clear cell areas and had an approximately similar proliferative index. The inflammatory component was mixed (lymphocytes, histiocytes, plasma cells, neutrophils) but was composed predominantly of CD45/CD3/CD8 T lymphocytes, with a CD3 to CD20 ratio of approximately 10:1 and CD8 to CD4 T-cell ratio of approximately 3:1. Numerous (>100 positive cells per 10 high-power fields) S100-positive tumor-infiltrating Langerhans cells were present. The tumor DNA did not exhibit microsatellite instability at any of the loci analyzed. In summary, the limited data available suggest that lymphoepithelioma-like carcinoma is a distinct histotype of endometrial carcinoma that is typically seen in postmenopausal women, seems to be unrelated to the Epstein-Barr virus, and has an uncertain prognosis. Differential diagnostic and pathogenetic considerations are discussed within the context of the lesional morphologic and immunophenotypic profile as described herein and in previously reported cases.
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PMID:Lymphoepithelioma-like carcinoma of the endometrium: immunophenotypic characterization of a rare tumor with microsatellite instability testing. 2430 May 38

Lymph node (LN) macrophages play critical roles in anti-tumor immunity, which develops via the activation of cytotoxic T cells (CTL) and NK cells. The present study aims to determine the prognostic significance of CD169(+) LN macrophages in patients with endometrial carcinoma (EC). The number of CD169(+) cells or the CD169(+) -to-CD68(+) macrophage ratio in regional LN (RLN), and the number of CD8(+) CTL or CD57(+) NK cells in tumor tissues were investigated by immunohistochemistry in paraffin-embedded tissue samples from 79 patients with EC. A high density of CD169(+) cells in the RLN of patients with EC was correlated with an early clinical stage or no LN metastasis. A high number of CD169(+) cells and a high CD169(+) -to-CD68(+) macrophage ratio were significantly associated with longer overall survival in EC. We also found that the density of CD169(+) macrophages was positively correlated with the number of CD8(+) CTL and CD57(+) NK cells that infiltrated into tumor tissues. A high density of CD57(+) cells in EC tissues was associated with a better prognosis, while a high density of CD8(+) cells was not linked to an altered prognosis. The present study showed that the density of CD169(+) macrophages in RLN was associated with an improved prognosis in EC patients. CD169(+) macrophages in RLN might represent a useful marker for assessing clinical prognoses and monitoring anti-tumor immunity in patients with EC.
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PMID:Prognostic significance of CD169-positive lymph node sinus macrophages in patients with endometrial carcinoma. 2699 48


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