POTENTIAL LIFE PROGNOSTIC MARKER FOR MESENCHYMAL TUMOR RESEMBLING UTERINE LEIOMYOSARCOMA.

Benign uterine leiomyoma (U.LMA) and malignant uterine leiomyosarcoma (U.LMS), both uterine mesenchymal tumors, are distinguished by the number of cells exhibiting mitotic activity. However, uterine mesenchymal tumors contain tumor cells with various cell morphologies; therefore, making a diagnosis, including differentiating between benign and malignant tumors, is difficult. For example, cotyledonoid dissecting leiomyoma (CDL) or uterine smooth muscle tumors of uncertain malignant potential (STUMPs) are a group of uterine mesenchymal tumors for which a differential diagnosis is challenging. To date, a standardized classification system for uterine mesenchymal tumors has not yet been established. Furthermore, definitive preoperative imaging techniques or hematological examinations for the potential inclusion of CDL or STUMP in the differential diagnosis have not been defined. Several clinical studies have reported that there is no correlation between biomarker expression and mitotic rate or tumor recurrence. The immunohistochemical biomarkers reported so far cannot effectively help determine the malignant potential of CDL or STUMPs in patients who wish to become pregnant in the future. The establishment of gene expression profiles or detection of pathogenic variants by using next-generation molecular techniques can facilitate disease prediction, diagnosis, treatment, and prognosis. We examined the oncological properties of STUMP in adults using molecular pathological techniques on tissue excised from patients with uterine mesenchymal tumor. In a clinical study conducted by our medical team, the results of gene expression profiling indicated factors that may be associated with malignancy of uterine mesenchymal tumors. We herein describe the problems in diagnosing uterine mesenchymal tumors along with the results of the latest clinical studies. It is expected that the establishment of a diagnostic method targeting the characteristics of mesenchymal tumor cells will lead to the treatment of malignant tumors with a low risk of recurrence and metastasis.

Frequency and risk factors of thoracic metastases and optimisation of the use of cross-sectional chest imaging in follow-up patients with cervical cancer.

AIM: To optimise cross-sectional chest imaging usage by identifying frequency and risk factors associated with thoracic metastases in cervical cancer patients after initial definitive treatment. MATERIALS AND METHODS: This study, conducted during 2004-2015, examined 361 consecutive patients with histopathologically proven cervical carcinoma with at least 1 year of follow-up. Electronic medical records and all available imaging modes were used to record and assess patient and tumour characteristics and timing of thoracic metastases. Associations with these characteristics and thoracic metastases were assessed using univariate and multivariable Cox proportional hazards modelling. RESULTS: Of the 361 patients, 31 developed thoracic metastases. Multivariate regression results showed that adeno/adenosquamous carcinomas (hazard ratio [HR], 2.46; 95% confidence interval [CI], 1.06 to 5.72), other histology (HR, 5.61; 95% CI, 1.81 to 17.42), high International Federation of Gynaecology and Obstetrics (FIGO) stage (HR, 2.84; 95% CI, 1.09 to 7.37), and presence of initial intra-abdominal lymph node metastases (HR, 2.46; 95% CI, 1.02 to 5.90) were associated significantly and independently with thoracic metastases. The second analysis among the subgroup of surgical treatment identified intermediate-high risk classification of recurrence (HR, 5.12; 95% CI, 1.14 to 22.94), high FIGO stage (HR, 2.73; 95% CI, 1.05 to 7.13), and other histology (HR, 11.51; 95% CI, 3.66 to 36.19) as independent predictors of thoracic metastases. Two of the 361 and 2/313 patients with thoracic metastases who did not correspond to the conditions above were in the respective evaluation groups. CONCLUSION: Assessment of negative prognostic factors for thoracic metastases might contribute to reduced need for chest cross-sectional chest computed tomography examinations.

IFN-γ from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer.

BACKGROUND: PD-L1 (programmed cell death 1 ligand 1) on tumour cells suppresses host immunity through binding to its receptor PD-1 on lymphocytes, and promotes peritoneal dissemination in mouse models of ovarian cancer. However, how PD-L1 expression is regulated in ovarian cancer microenvironment remains unclear. METHODS: The number of CD8-positive lymphocytes and PD-L1 expression in tumour cells was assessed in ovarian cancer clinical samples. PD-L1 expression and tumour progression in mouse models under conditions of altering IFN-γ signals was assessed. RESULTS: The number of CD8-positive cells in cancer stroma was very high in peritoneally disseminated tumours, and was strongly correlated to PD-L1 expression on the tumour cells (P<0.001). In mouse models, depleting IFNGR1 (interferon-γ receptor 1) resulted in lower level of PD-L1 expression in tumour cells, increased the number of tumour-infiltrating CD8-positive lymphocytes, inhibition of peritoneal disseminated tumour growth and longer survival (P=0.02). The injection of IFN-γ into subcutaneous tumours induced PD-L1 expression and promoted tumour growth, and PD-L1 depletion completely abrogated tumour growth caused by IFN-γ injection (P=0.01). CONCLUSIONS: Interferon-γ secreted by CD8-positive lymphocytes upregulates PD-L1 on ovarian cancer cells and promotes tumour growth. The lymphocyte infiltration and the IFN-γ status may be the key to effective anti-PD-1 or anti-PD-L1 therapy in ovarian cancer.