An Uncommon Presentation of Carcinosarcoma of the Stomach and a Minimally Invasive Approach for Treatment.

Carcinosarcoma is a rare malignant neoplasm that is composed of both epithelial and mesenchymal tumor components. Gastric carcinosarcoma is even more rare and is often diagnosed at a late stage. In this report, we investigate a case of early gastric carcinosarcoma with regional lymph node metastasis in a 78-year-old woman. The patient underwent partial gastrectomy, lymphadenectomy, and splenectomy. The tumor was confined to the gastric submucosa, and a biopsy specimen led to a histological diagnosis of carcinosarcoma with adenocarcinoma, squamous-cell carcinoma, and undifferentiated pleomorphic sarcoma components. Metastasis was present in one lymph node and displayed osteosarcomatous differentiation. Vigilant monitoring for recurrence and metastatic disease will be required for this patient.

Siglec-15 as an immune suppressor and potential target for normalization cancer immunotherapy.

Overexpression of the B7-H1 (PD-L1) molecule in the tumor microenvironment (TME) is a major immune evasion mechanism in some patients with cancer, and antibody blockade of the B7-H1/PD-1 interaction can normalize compromised immunity without excessive side-effects. Using a genome-scale T cell activity array, we identified Siglec-15 as a critical immune suppressor. While only expressed on some myeloid cells normally, Siglec-15 is broadly upregulated on human cancer cells and tumor-infiltrating myeloid cells, and its expression is mutually exclusive to B7-H1, partially due to its induction by macrophage colony-stimulating factor and downregulation by IFN-γ. We demonstrate that Siglec-15 suppresses antigen-specific T cell responses in vitro and in vivo. Genetic ablation or antibody blockade of Siglec-15 amplifies anti-tumor immunity in the TME and inhibits tumor growth in some mouse models. Taken together, our results support Siglec-15 as a potential target for normalization cancer immunotherapy.

Fibrinogen-like Protein 1 Is a Major Immune Inhibitory Ligand of LAG-3.

Lymphocyte-activation gene 3 (LAG-3) is an immune inhibitory receptor, with major histocompatibility complex class II (MHC-II) as a canonical ligand. However, it remains controversial whether MHC-II is solely responsible for the inhibitory function of LAG-3. Here, we demonstrate that fibrinogen-like protein 1 (FGL1), a liver-secreted protein, is a major LAG-3 functional ligand independent from MHC-II. FGL1 inhibits antigen-specific T cell activation, and ablation of FGL1 in mice promotes T cell immunity. Blockade of the FGL1-LAG-3 interaction by monoclonal antibodies stimulates tumor immunity and is therapeutic against established mouse tumors in a receptor-ligand inter-dependent manner. FGL1 is highly produced by human cancer cells, and elevated FGL1 in the plasma of cancer patients is associated with a poor prognosis and resistance to anti-PD-1/B7-H1 therapy. Our findings reveal an immune evasion mechanism and have implications for the design of cancer immunotherapy.

Hormone producing gynecological tumors: pathologic entities and clinical significance.

INTRODUCTION: Due to their derivation from the cell types involved in gynecologic hormonal networks, many gynecologic tumors may produce hormones. In a normal physiological setting, these hormones are essential for regulating the biology and function of gynecological organs, the ovary and uterus in particular. Overproduction of hormones by the tumor may lead to abnormal clinical manifestations of the patients and spillage of excess hormonal products into the blood. Abnormal elevation of serum hormones may be considered as biomarkers that are important to pathologists and clinicians in making precise tumor diagnoses and likely useful in monitoring the tumor burden/recurrence to guide patient treatment options. This review will discuss gynecologic neoplasms that produce hormonal biomarkers and assess their relevance to pathological diagnosis, evaluation for therapeutic response and monitoring disease progression. AREAS COVERED: Studies involving hormonal production by a gynecologic tumor were candidates for inclusion in this review. EXPERT COMMENTARY: Serum hormonal biomarkers have clinical utility both in the diagnosis of gynecologic neoplasms and clinical monitoring of treatment efficacy and recurrence.

Strong androgen receptor expression can aid in distinguishing GATA3+ metastases.

GATA3 is a transcription factor used clinically as a marker of breast or urothelial differentiation. A marker is yet needed to distinguish this in the case of the GATA3-positive tumor of unknown origin. We tested classical markers of breast differentiation and hormonal signaling to see which correlated strongest with GATA3 expression in breast cancer and thus which could help correctly identify breast origin in the case of the GATA3-positive tumor of unknown origin. GATA3, estrogen receptor, progesterone receptor, androgen receptor (AR), HER2, GCDFP15, and mammaglobin expression was intercorrelated in a histologically diverse 259-case breast cancer tissue microarray. We show herein a uniquely high level of correlation between GATA3 and AR expression (r=0.61; 95% confidence interval 0.52-0.68) that was strongest among lobular carcinomas (r=1; 95% confidence interval 0.73-1) and stronger than any other correlation studied. Separate AR staining of 10 metastatic GATA3+ carcinomas of urothelial origin and 13 metastatic GATA3+ carcinomas of breast origin showed that strong AR staining (>60% of tumor cells) has a sensitivity of 54% and a specificity of 100% for correctly distinguishing GATA3+ carcinoma of mammary origin from urothelial origin in the metastatic setting. Androgen receptor expression is strongly correlated with GATA3 in breast cancer, particularly in tumors with lobular morphology. Strong AR expression (>60% of tumor cells) is an excellent test to rule out urothelial carcinoma in the GATA3+ metastatic setting (specificity 100%) and will effectively identify breast origin in approximately 50% of cases.