Comprehensive assessment of the expression of the SWI/SNF complex defines two distinct prognostic subtypes of ovarian clear cell carcinoma.

Somatic mutations in the ARID1A tumor-suppressor gene have been frequently identified in ovarian clear cell carcinoma (CCC) cases. BAF250a encoded by ARID1A is a member of the SWI/SNF complex, but the expression and mutation status of other SWI/SNF subunits have not been explored. The current study aimed to elucidate the biological and clinical significance of the SWI/SNF complex subunits, by assessing the expression and mutation status of SWI/SNF subunits, and distinct genomic aberrations associated with their expression. Of 82 CCC specimens, 38 samples presented no BAF250a expression, and 50 samples exhibited the loss of at least one subunit of the SWI/SNF complex. Cases which lack at least one SWI/SNF complex component exhibited significantly more advanced stages, faster growth and stronger nuclear atypia compared with SWI/SNF-positive samples (p<0.05). Although BAF250a expression is not related to poor prognosis, the group presenting the loss of at least one SWI/SNF complex subunit exhibited significantly shorter overall and progression-free survivals (p<0.05). A multivariate analysis suggested that the expression status of the SWI/SNF complex serves as an independent prognostic factor (p<0.005). The cases positive for all SWI/SNF subunits demonstrated significantly greater DNA copy number alterations, such as amplification at chromosomes 8q.24.3 and 20q.13.2-20q.13.33 (including ZNF217) and deletion at chromosomes 13q12.11-13q14.3 (including RB1), 17p13.2-17p13.1 (including TP53) and 19p13.2-19p13.12. In conclusion, the CCCs exhibiting the loss of one or multiple SWI/SNF complex subunits demonstrated aggressive behaviors and poor prognosis, whereas the CCCs with positive expression for all SWI/SNF components presented more copy number alterations and a favorable prognosis.

Assessment of the early predictive power of quantitative magnetic resonance imaging parameters during neoadjuvant chemotherapy for uterine cervical cancer.

OBJECTIVES: The purpose of this study was to quantitatively evaluate 3 types of magnetic resonance imaging (MRI) parameters in parallel for the early prediction of neoadjuvant chemotherapy (NACT) effectiveness in cervical cancer-tumor volume parameters, diffusion parameters, and perfusion parameters. MATERIALS AND METHODS: We prospectively evaluated 13 patients with International Federation of Gynecology and Obstetrics stage IB to IIB cervical squamous cell carcinoma who underwent 3 serial MRI studies, that is, pretreatment, post-first course NACT, and post-second course NACT followed by radical hysterectomy. We obtained tumor volume parameters, diffusion parameters, and dynamic contrast material-enhanced perfusion parameters quantitatively from pretreatment MRI and post-first course MRI. The correlation of these parameters and the eventual tumor volume regression rate (TVRR) obtained from pretreatment MRI and post-second course MRI before surgery were investigated, statistically based on the Pearson correlation coefficient. RESULTS: Thirteen patients had a total of 39 scans. Early TVRR (r = 0.844; P < 0.001), the fractional volume of the tissue extracellular extravascular space (Ve, r = 0.648; P < 0.05), and the change of Ve during the first course of NACT (r = -0.638; P < 0.05) correlated with eventual TVRR. CONCLUSIONS: Early TVRR, Ve, and the change of Ve could be useful predictors for the treatment effectiveness of NACT. These parameters could help to modify strategy in the early stage of NACT and to choose individualized treatment to avoid the delay of radical treatment, even when NACT is ineffective.

The comprehensive assessment of local immune status of ovarian cancer by the clustering of multiple immune factors.

The aim of this study was to evaluate the local immune status of human ovarian cancers by the comprehensive analysis of tumor-infiltrating immune cells and immunosuppressive factors, and to elucidate the local immunity in clinical course. The numbers of CD1α+, CD4+, CD8+, CD57+, forkhead box P3+ and programmed cell death-1+ cells were counted, and the intensity of immunosuppressive factors, such as programmed cell death-1 ligand (PD-L)1, PD-L2, cyclooxygenase (COX)-1, COX-2 and transforming growth factor ß1, were evaluated in 70 ovarian cancer specimens stained by immunohistochemistry. Then hierarchical clustering of these parameters showed the four clusters into ovarian cancer cases. Cluster 1, which had significantly better prognosis than the others, was characterized by high infiltration of CD4+ and CD8+ cells. In conclusion the comprehensive analysis of local immune status led to subdivide ovarian cancers into groups with better or worse prognoses and may guide precise understanding of the local immunity.