When we examined the presence of ITB as a maker of destructive stromal invasion of SOCs, it was found to be a significant poor prognostic indicator for the PFS of women with SOC, but did not reach statistical significance for the OS of women with SOC in the univariate analysis. In a multivariate analysis, ITB was not an independent prognostic indicator. The prognostic significance of ITB was considered to be strongly affected by the 2014 FIGO stage. The large size studies stratified by the 2014 FIGO stage may be recommended.
It is well-known that TBs are part of the tumor microenvironment and are associated with epithelial-mesenchymal transition (EMT) 7. EMT is characterized by cytoskeletal rearrangements, cell motility and invasion, increased cell-associated proteolytic activity and reprogramming of the gene expression14. Although the association between ITB and lymph node metastasis did not reach statistical significance, ITB was significantly associated with the incidence of LVSI in the present study. Increasing evidence has highlighted a close relationship between EMT and chemoresistance in epithelial ovarian carcinoma (EOC) 15. In one study, the SKOV-3 EOC cells were shown to trigger both EMT and chemoresistance after treatment by carboplatin 16. ITB was found in all SOCs after NAC, except for in two complete regression cases, and was associated with a low mitotic index of tumors and poor prognosis of patients.
The stromal-epithelial patterns of invasion in SBTs of the ovary have been subclassified as destructive and nondestructive. By definition, well-differentiated serous tumors featuring destructive stromal invasion are classified as low-grade serous carcinomas whereas those with either no stromal invasion or stromal microinvasion are classified as SBTs of the ovary 17. In a review, low-grade serous carcinoma was defined as a serous neoplasm showing destructive invasion, mild to moderate cytologic atypia, and relatively low proliferative activity. Low-grade serous carcinoma accounts for 4.7% of SOCs and has an excellent prognosis, but long-term follow-up indicates that the prognosis for patients with stage III-IV disease is poor 18. In the present study, 3 SOCs without ITB and 1 SOC with ITB (5.6%) showed both histologic features of mild to moderate nuclear atypia and ≤ 12 mitoses/10 HPFs in 71 SOCs without NAC.
Analyses of gene expression microarray data from The Cancer Genome Atlas (TCGA) project revealed that high-grade SOC could be classified as one of four gene expression subtypes: mesenchymal, immunoreactive, proliferative, or differentiated 19. Tumors with the mesenchymal phenotype had poor prognoses, whereas those with the immunoreactive type had favorable prognoses. Murakami et al. 20 said that a feature of spindle and isolated cells with destructive stromal reaction was referred to as the mesenchymal phenotype. Tothill et al. 21 reported that a novel subtype of high-grade serous cancers reflected a mesenchymal cell type, characterized by the overexpression of N-cadherin and P-cadherin and low expression of differentiation markers, including CA125 and MUC1. A poor prognosis subtype was defined by a reactive stroma gene expression signature, correlating with extensive desmoplasia in such samples.
In conclusion, recent studies concerning the origin and molecular pathogenesis of SOCs support the performance of prophylactic salpingo-oophorectomy in high-risk women and new molecular target therapy in women with high-grade SOC. ITB was shown to be a cost-effective prognostic indicator for women with SOC and a histopathologic biomarker of the progression of SOC. We may need to pay closer attention to the progression of SOCs