Evaluation of Microinvasion and Lymph Node Involvement in Ovarian Serous Borderline/Atypical Proliferative Serous Tumors A Morphologic and Immunohistochemical Analysis of 37 Cases

Most of the literature on serous borderline/atypical proliferative serous tumors (SBT/APSTs) shows no effect of microinvasion or lymph node involvement on outcome. This study is a morphologic and immunohistochemical analysis of the cells comprising SBT/APSTs, microinvasion, lymph node involvement, and low-grade serous carcinoma (LGSC) in an attempt to explain this unusual behavior. We found that the cells in microinvasion and in lymph nodes were morphologically similar to the cells in SBT/APSTs but differed significantly from the cells in LGSCs. In addition, one particular population of cells, those with abundant eosinophilic cytoplasm (eosinophilic cells), in SBT/APSTs, microinvasion, and lymph nodes showed a significant loss of expression of ER, PR, and WT-1 compared with the cuboidal/columnar tumor cells, both in cases of microinvasion (P<0.001 for all 3 markers) and lymph node involvement (P<0.001, P=0.02, P=0.002, respectively). There was a significant decrease in the Ki-67 proliferation index for microinvasion (P=0.004) and a decreasing trend for lymph node involvement (nonsignificant) compared with the columnar/cuboidal cells. In addition, cells in these tumors showed morphologic evidence of apoptosis, which was confirmed by immunostaining with M30, a marker of apoptosis. In contrast, LGSCs lacked eosinophilic cells and showed no loss of expression of ER, PR, and WT-1. They also had a significantly higher Ki-67 proliferation index than their associated SBT/APSTs (P=0.029). On the basis of these findings, we propose that the cells comprising microinvasion do not represent an invasive neoplastic process. Instead, in view of the loss of expression of ER, PR, and WT-1, evidence of apoptosis, and decrease in the Ki-67 proliferation index, we postulate that they are senescent and terminally differentiated with a subset of cells undergoing apoptosis, which could explain their lack of an adverse effect on outcome.