Multidirectional Differentiation of Endometrial Carcinoma with Special Reference to Tumor Aggressiveness Evaluated by Ki-67 Expression

To clarify the correlation between multidirectional differentiation and aggressiveness of endometrial adenocarcinomas, we assessed both proliferative activities (PA) using Ki-67 expression and squamous and/or endocrine differentiation. We divided 51 adenocarcinomas into 22 adenocarcinomas with typical squamous differentiation (≥10% of tumor cells, typical SQ) classified into 10 adenoacanthomas (AA) and 12 adenosquamous carcinomas (AS), 17 adenocarcinomas with focal squamous differentiation (<10% of tumor cells), and 12 typical adenocarcinomas without morphological squamous differentiation (pure AC), according to the new WHO classification. Paraffin-embedded sections were stained using monoclonal antibodies against high-molecular-weight keratins (HMWK) to recognize squamous cells, chromogranin A to recognize endocrine cells, and Ki-67 antigen to recognize proliferating cells. Both AA and AS exhibited lower PA than pure AC. Typical SQ exhibited lower PA than pure AC. This difference was also significant after selecting only grade 1 or stage I/II cases. AA exhibited lower PA than AS and also after selecting only grade 1 or stage I/II cases. PA of adenocarcinoma with the expression of HMWK in ≥30% of tumor cells was lower than those without HMWK. PA of adenocarcinoma with the expression of chromogranin A in ≥10% of tumor cells was lower than those without chromogranin A. These differences were also significant after selecting only grade 1 or stage I/II cases. Squamous and/or endocrine differentiation is a good marker for a reduction of PA. Endometrial adenocarcinomas with multidirectional differentiation exhibited lower PA and were likely to be more mature than those with monodirectional differentiation.