Extragenital endometrial stromal sarcoma of transverse mesocolon: A diagnostic conundrum

Endometrial stromal sarcoma (ESS) is a rare uterine neoplasm infrequently arising in extra-genital sites. Herein, we report an extremely rare case of primary extra-genital ESS of transverse mesocolon occurring in a 51-year-old female presenting with gradually increasing abdominal mass. The clinical diagnosis considered was a gastrointestinal stromal tumor. Intra-operatively, the mass was confined exclusively to the transverse mesocolon. Microscopy revealed a cellular tumor composed of oval to elongate neoplastic cells with hyperchromatic nuclei, inconspicuous nucleoli and were immunoreactive for CD10, progesterone receptor (PR), estrogen receptor (ER), and PAX8; negative for KIT, CD34, SMA, S100, synaptophysin, chromogranin, WT-1, and calretinin. A distinct arborizing network of arterioles along with foci of endometriosis was also seen. We present this case for its extreme rarity and the challenges entailed in its diagnosis.

The PGRMC1 Antagonist AG-205 Inhibits Synthesis of Galactosylceramide and Sulfatide

Sulfatide synthesis in the human renal cancer cell line SMKT-R3 was strongly inhibited in the presence of low µM concentrations of AG-205, a progesterone receptor membrane component 1 (PGRMC1) antagonist. This was also the case in Chinese hamster ovary (CHO) cells stably transfected with UDP-galactose: ceramide galactosyltransferase and cerebroside sulfotransferase, the two enzymes required for sulfatide synthesis. In CHO cells synthesizing galactosylceramide but not sulfatide, galactosylceramide was also strongly reduced, suggesting an effect at the level of galactolipid synthesis. Notably, AG-205 inhibited galactosylceramide synthesis to a similar extent in wild type CHO cells and cells that lack PGRMC1 and/or PGRMC2. In vitro enzyme activity assays showed that AG-205 is an inhibitor of UDP-galactose: ceramide galactosyltransferase, but not cerebroside sulfotransferase. This study shows that PGRMC1 is only one of several targets of AG-205 and should be used with caution, especially in studies using cells synthesizing galactosylceramide and sulfatide.

Application of preoperative ultrasound features combined with clinical factors in predicting HER2-positive subtype (non-luminal) breast cancer

Background Human epidermal growth factor receptor2+ subtype breast cancer has a high degree of malignancy and a poor prognosis. The aim of this study is to develop a prediction model for the human epidermal growth factor receptor2+ subtype (non-luminal) of breast cancer based on the clinical and ultrasound features related with estrogen receptor, progesterone receptor, and human epidermal growth factor receptor2. Methods We collected clinical data and reviewed preoperative ultrasound images of enrolled breast cancers from September 2017 to August 2020. We divided the data into in three groups as follows. Group I: estrogen receptor ± , Group II: progesterone receptor ± and Group III: human epidermal growth factor receptor2 ± . Univariate and multivariate logistic regression analyses were used to analyze the clinical and ultrasound features related with biomarkers among these groups. A model to predict human epidermal growth factor receptor2+ subtype was then developed based on the results of multivariate regression analyses, and the efficacy was evaluated using the area under receiver operating characteristic curve, accuracy, sensitivity, specificity. Results The human epidermal growth factor receptor2+ subtype accounted for 138 cases (11.8%) in the training set and 51 cases (10.1%) in the test set. In the multivariate regression analysis, age ≤ 50 years was an independent predictor of progesterone receptor + (p = 0.007), and posterior enhancement was a negative predictor of progesterone receptor + (p = 0.013) in Group II; palpable axillary lymph node, round, irregular shape and calcifications were independent predictors of the positivity for human epidermal growth factor receptor-2 in Group III (p = 0.001, p = 0.007, p = 0.010, p < 0.001, respectively). In Group I, shape was the only factor related to estrogen receptor status in the univariate analysis (p < 0.05). The area under receiver operating characteristic curve, accuracy, sensitivity, specificity of the model to predict human epidermal growth factor receptor2+ subtype breast cancer was 0.697, 60.14%, 72.46%, 58.49% and 0.725, 72.06%, 64.71%, 72.89% in the training and test sets, respectively. Conclusions Our study established a model to predict the human epidermal growth factor receptor2-positive subtype with moderate performance. And the results demonstrated that clinical and ultrasound features were significantly associated with biomarkers.

Progesterone Receptor Membrane Component 1 and Its Accomplice: Emerging Therapeutic Targets in Lung Cancer

: Progesterone receptor membrane component 1 (PGRMC1) is a trans-membrane evolutionarily conserved protein with a cytochrome b5 like heme/steroid binding domain. PGRMC1 clinical levels are strongly suggested to correlate with poor patient survival and lung cancer prognosis. PGRMC1 has been reported to possess pleiotropic functions, such as participating in cellular and membrane trafficking, steroid hormone signaling, cholesterol metabolism and steroidogenesis, glycolysis and mitochondrial energy metabolism, heme transport and homeostasis, neuronal movement and synaptic function, autophagy, anti-apoptosis, stem cell survival and the list is still expanding. PGRMC1 mediates its pleiotropic functions through its ability to interact with multiple binding partners, such as epidermal growth factor receptor (EGFR), sterol regulatory element binding protein cleavage activating protein (SCAP), insulin induced gene-1 protein (Insig-1), heme binding proteins (hepcidin, ferrochelatase and cyp450 members), plasminogen activator inhibitor 1 RNA binding protein (PAIR-BP1). In this review, we provide a comprehensive overview of PGRMC1 and its associated pleiotropic functions that are indispensable for lung cancer promotion and progression, suggesting it as a prospective therapeutic target for intervention. Notably, we have compiled and reported various preclinical studies wherein prospective agonists and antagonists had been tested against PGRMC1 expressing cancer cell lines, suggesting it as a prospective therapeutic target for cancer intervention.