Clinical characteristics and survival of patients with normal-sized ovarian carcinoma syndrome: Retrospective analysis of a single institution 10-year experiment.

BACKGROUND: Normal size ovarian cancer syndrome (NOCS) is a challenge for clinicians regarding timely diagnosis and management due to atypical clinical and imaging features. It is extremely rare with only a few cases reported in the literature. More data are needed to clarify its biological behavior and compare the differences with abnormal size ovarian cancer. AIM: To assess the clinical and pathological features of NOCS patients treated in our institution in the last 10 years and to explore risk factors for relapse and survival. METHODS: Patients who were pathologically diagnosed with NOCS between 2008 and 2018 were included. Papillary serous ovarian carcinoma (PSOC) patients were initially randomly recruited as the control group. Demographics, tumor characteristics, treatment procedures, and clinical follow-up were retrospectively collected. Risk factors for progression-free survival and overall survival were assessed. RESULTS: A total of 110 NOCS patients were included; 80 (72.7%) had primary adnexal carcinoma, two (1.8%) had mesotheliomas, 18 (16.4%) had extraovarian peritoneal serous papillary carcinoma, and eight (7.3%) had metastatic tumors. Carbohydrate antigen (CA)125 and ascites quantity were lower in the NOCS cohort than in the PSOC group. The only statistically significant risk factors for worse overall survival (P < 0.05) were the levels of CA199 and having fewer than six chemotherapy cycles. The 1-year, 3-year, and 5-year survival rates were 75.5%, 27.7%, and 13.8%, respectively. CONCLUSION: The clinical symptoms of the NOCS group are atypical, and the misdiagnosis rate is high. Ascites cytology and laparoscopic exploration are valuable in the early diagnosis to avoid a misdiagnosis. The level of CA199 is the most important predictor of overall survival, and more than six cycles of chemotherapy contributes to the increased survival rates of NOCS patients.

Tumor-associated Lymphatic Endothelial Cells Promote Lymphatic Metastasis By Highly Expressing and Secreting SEMA4C.

PURPOSE: Lymphatic vessels are mainly regarded as passive conduits for the dissemination of cancer cells. In this study, we investigate whether and how the tumor-associated lymphatic vessels may play an active role in tumor metastasis. EXPERIMENTAL DESIGN: In situ laser capture microdissection of lymphatic vessels followed by cDNA microarray analysis was used to determine the expression profiling of lymphatic endothelial cells (LEC). Gene expression levels and activity of signaling pathways were measured by real-time RT-PCR, ELISA, or immunoblotting. Lymphangiogenesis was assessed by IHC. Lymph node metastasis was measured using fluorescence imaging. The effects of SEMA4C on lymphangiogenesis in vitro were evaluated using migration assay and tube-formation assay of LECs. RESULTS: Tumor-associated LECs are molecularly and functionally different from their normal counterparts. In addition to expressing high levels of membrane-bound SEMA4C, tumor-associated LECs also produced soluble SEMA4C (sSEMA4C). Increased serum sSEMA4C was detected in patients with breast cancer and cervical cancer. Patients with metastasis had much higher levels of serum sSEMA4C. sSEMA4C promoted lymphangiogenesis by activating PlexinB2-ERBB2 signaling in LECs, and promoted the proliferation and migration of tumor cells by activating PlexinB2-MET signaling, thus promoting lymphatic metastasis. Although the SEMA4C signaling pathways differ between LECs and tumor cells, RHOA activation was necessary for the effects of SEMA4C in both types of cells. CONCLUSIONS: Tumor-associated LECs produce sSEMA4C to promote lymphatic metastasis of tumors. Our results suggest that SEMA4C and RHOA might be potential therapeutic targets, and that higher serum sSEMA4C could be a marker for breast cancer and cervical cancer. Clin Cancer Res; 23(1); 214-24. ©2016 AACR.

Knockdown of ezrin suppresses the migration and angiogenesis of human umbilical vein endothelial cells in vitro.

Progressive tumor growth is dependent on angiogenesis. The mechanisms by which endothelial cells (ECs) are incorporated to develop new blood vessels are not well understood. Recent studies reveal that the ezrin radixin moesin (ERM) family members are key regulators of cellular activities such as adhesion, morphogenetic change, and migration. We hypothesized that ezrin, one of the ERM family members, may play important roles in ECs organization during angiogenesis, and new vessels formation in preexisting tissues. To test this hypothesis, in this study, we investigated the effects of ezrin gene silencing on the migration and angiogenesis of human umbilical vein endothelial cells (HUVECs) in vitro. HUVECs were transfected with plasmids with ezrin-targeting short hairpin RNA by using the lipofectamine-2000 system. Wound assay in vitro and three-dimensional culture were used to detect the migration and angiogenesis capacity of HUVECs. The morphological changes of transfected cells were observed by confocal and phase contrast microscopy. Our results demonstrated that the decreased expression of ezrin in HUVECs significantly induced the morphogenetic changes and cytoskeletal reorganization of the transfected cells, and also reduced cell migration and angiogenesis capacity in vitro, suggesting that ezrin play an important role in the process of HUVECs migration and angiogenesis.

[Effects of vimentin on invasion and metastasis of prostate cancer cell lines PC-3M-1E8 and PC-3M-2B4].

BACKGROUND & OBJECTIVE: Vimentin, a cytoskeleton protein, is involved in regulating the migration and proliferation of cells. This study was to detect the expression of vimentin in prostate cancer cell lines PC-3M-1E8 and PC-3M-2B4, and evaluate the effects of vimentin on invasion and metastasis of prostate cancer cells. METHODS: Two-dimensional gel electrophoresis (2-DE) followed by matrix-assisted laser desorption/time of flight mass spectrometry (MALDI TOF-MS) were used to detect the expression of vimentin in prostate cancer cell lines PC-3M-1E8 and PC-3M-2B4. Genetic intervention of vimentin gene and in vitro invasion assay were used to investigate the effects of vimentin on the invasion and metastasis of prostate cancer cells. RESULTS: The protein level of vimentin was higher in PC-3M-1E8 cells with high metastatic potential than in PC-3M-2B4 cells with low metastatic potential. Eukaryotic vectors expressing antisense-and sense-vimentin were constructed successfully and transfected into PC-3M-1E8 and PC-3M-2B4 cells separately. The number of invasive cells was significantly lower in PC-3M-1E8/vas cells with antisense-vimentin than in control PC-3M-1E8/3.1(-) cells (99.3+/-4.8 vs. 319.4+/-6.5, P<0.01), and significantly higher in PC-3M-2B4/vs cells with sense-vimentin than in control PC-3M-2B4/3.1(+) cells (330.5+/-5.8 vs. 98.6+/-7.5, P<0.01). CONCLUSION: Vimentin is a promising marker for predicting the invasion and metastasis of prostate cancer cells.

[Expression of Ezrin and E-cadherin in invasive ductal breast cancer and their correlations to lymphatic metastasis].

BACKGROUND & OBJECTIVE: Ezrin, a cytoskeleton linker protein, is actively involved in regulating the growth and metastasis of cancer cells. This study was performed to detect the expression of Ezrin and E-cadherin in primary invasive ductal breast cancer in order to evaluate their possible roles in lymphatic metastasis. METHODS: The expression of Ezrin and E-cadherin in 60 specimens of primary invasive ductal breast cancer (23 with metastasis, 37 without metastasis) was detected by SP immunohistochemistry. RESULTS: The abnormal expression rates of Ezrin and E-cadherin were significantly higher in the cases with metastasis than in the cases without metastasis (73.91% vs. 51.35%, P=0.039; 65.22% vs. 40.54%, P<0.001). The abnormal expression of Ezrin was positively correlated to that of E-cadherin (r=0.898, P=0.038). CONCLUSION: Ezrin and E-cadherin are closely related to invasion and metastasis of ductal breast cancer, suggesting that they are important tumor markers in predicting lymphatic metastasis of invasive ductal breast cancer.