Transcriptional co-activator with PDZ-binding motif (TAZ), a downstream effector of the Hippo pathway, has been reported to regulate organ size, tissue homeostasis, and tumorigenesis by acting as a transcriptional co-activator. Lysophosphatidic acid (LPA) is a bioactive lipid implicated in tumorigenesis and metastasis of ovarian cancer through activation of G protein-coupled receptors. However, the involvement of TAZ in LPA-induced tumorigenesis of ovarian cancer has not been elucidated. In order to demonstrate the role of TAZ in LPA-stimulated tumorigenesis, the effects of LPA on TAZ expression and cell migration were determined by Western blotting and chemotaxis analyses in R182 human epithelial ovarian cancer cells. Treatment of R182 cells with the LPA receptor inhibitor Ki16425 blocked LPA-induced cell migration. In addition, transfection of R182 cells with small interfering RNA specific for LPA receptor 1 resulted in abrogation of LPA-stimulated cell migration. LPA induced phosphorylation of ERK and p38 MAP kinase in R182 cells and pretreatment of cells with the MEK-ERK pathway inhibitor U0126, but not the p38 MAPK inhibitor SB202190, resulted in abrogation of LPA-induced cell migration. Pretreatment of R182 cells with U0126 attenuated LPA-induced mRNA levels of TAZ and its transcriptional target genes, such as CTGF and CYR61, without affecting phosphorylation level of YAP. These results suggest that MEK-ERK pathway plays a key role in LPA-induced cell migration and mRNA expression of TAZ in R182 cells, without affecting stability of TAZ protein. In addition, small interfering RNA-mediated silencing of TAZ expression attenuated LPA-stimulated migration of R182 cells. These results suggest that TAZ plays a key role in LPA-stimulated migration of epithelial ovarian cancer cells.

Objective: The aim of the present study was to determine the prognostic significances of markers of preoperative systemic inflammatory response (SIR) in patients with ovarian clear cell carcinoma (OCCC).

Ovarian cancer is a fatal gynecological malignancy. Although first-line chemotherapy and surgical operation are effective treatments for ovarian cancer, its clinical management remains a challenge owing to intrinsic or acquired drug resistance and relapse at local or distal lesions. Cancer stem cells (CSCs) are a small subpopulation of cells inside tumor tissues, and they can self-renew and differentiate. CSCs are responsible for the cancer malignancy involved in relapses as well as resistance to chemotherapy and radiation. These malignant properties of CSCs are regulated by cell surface receptors and intracellular pluripotency-associated factors triggered by internal or external stimuli from the tumor microenvironment. The malignancy of CSCs can be attenuated by individual or combined restraining of cell surface receptors and intracellular pluripotency-associated factors. Therefore, targeted therapy against CSCs is a feasible therapeutic tool against ovarian cancer. In this paper, we review the prominent roles of cell surface receptors and intracellular pluripotency-associated factors in mediating the stemness and malignancy of ovarian CSCs.

Shin KH, et al. Ann Lab Med. 2020 Jan;40(1):40-47. https://doi.org/10.3343/alm.2020.40.1.40

Perivascular epithelioid cell tumor (PEComa) is a rare subtype of mesenchymal origin tumor composed of epithelioid cells which exhibits immunohistochemical co-expressions of melanocytic markers and smooth muscle markers. In the first case, malignant uterine PEComa with vaginal and multiple lung metastasis was misdiagnosed preoperatively as uterine leiomyosarcoma despite a preoperative punch biopsy and immunohistochemical analysis of the metastatic vaginal mass. In the second case, synchronous uterine PEComa showing benign histology with lymph node involvement was incidentally detected after a staging operation for ovarian cancer. Definitive diagnosis of uterine PEComa was achieved only after hysterectomy despite preoperative assessment with pelvic magnetic resonance imaging and punch biopsy of metastatic lesion. The authors report two rare cases of uterine PEComa diagnosed postoperatively based on the morphologic and immunohistochemical features.

Purpose: Preoperative diagnosis of uterine leiomyosarcoma (LMS) is challenging because the disease can mimic benign leiomyoma (LM). The objective of the present study was to investigate the role of preoperative clinical characteristics and hematologic parameters to differentiate uterine LMS and LM. Methods: Preoperative clinical and laboratory variables were reviewed retrospectively in patients with LMS or LM, and the significances of intergroup differences were assessed. Receiver operating characteristic (ROC) curves were used to determine optimal cut-off values for each variable. Logistic regression analysis was applied to identify variables predicting the presence of LMS. Results: The preoperative clinical and laboratory variables of 336 patients with uterine tumor were analyzed. Seventy-nine patients had LMS and 257 had LM. A significant difference was observed between LMS and LM in terms of the median value of age at diagnosis, menopausal status, white blood cell (WBC) count, absolute neutrophil count (ANC), C-reactive protein (CRP), lactate dehydrogenase (LDH), and neutrophil-to-lymphocyte ratio (NLR) (all P < 0.001). Multivariate analyses showed that menopausal status (odds ratio [OR] = 3.40, P= 0.002), WBC count (OR = 2.09, P = 0.012), ANC (OR = 3.17, P < 0.001), CRP (OR = 21.74, P < 0.001), LDH (OR = 10.77, P < 0.001), and NLR (OR = 2.58, P = 0.001) predicted the presence of LMS. Conclusion: Our results suggest that in older or postmenopausal patients, high WBC count, ANC, CRP, LDH, and NLR could be useful biomarkers for the differentiation of LMS and LM, which indicate that serum markers might be useful, cost-effective, and broadly available diagnostic markers for uterine LMS.