Detection and importance of micrometastases in histologically negative lymph nodes in endometrial carcinoma

Lymph node status is the most important prognostic factor in terms of its relation to long-term survival of endometrial carcinoma (EC) patients. We aimed to investigate the rate of micrometastases in lymph nodes of EC patients that were previously reported as negative with routine histopathology, and the relationship with clinical and pathologic factors.

With immunohistochemistry, we retrospectively looked at cytokeratin staining of lymph nodes from 47 EC patients, that were previously reported to be negative for lymph node metastases after full surgical staging and routine histopathologic investigation. We also looked at the relationship between micrometastases and clinical, histopathologic factors and recurrence.

Of all 47 patients, seven (14.9%) were found to have micrometastases in their previously negatively reported lymph nodes. Six out of seven of these patients (85.7%) were high-risk EC patients. Among high-risk EC patients, 50% had micrometastases, whereas only one patient out of 35 with low or intermediate risk had micrometastases (2.9%). The difference between these groups was statistically significant (p = 0.001). Grade was also correlated with micrometastases (p = 0.0001). Mean follow-up time was 55.5 +/- 13.3 months. There were two recurrences in the group having cytokeratin micrometastasis, whereas no patients without micrometastases developed any recurrence. While 36 months recurrence-free survival (RFS) was 100% in patients without micrometastases, it was 71% in patients with micrometastases (mean rate 57 months) (p = 0.0004). Both RFS and overall survival were statistically significantly inferior for patients having micrometastases, high-risk status, and lymphovascular space involvement (p < 0.05).

It seems reasonable to further analyze negative lymph nodes in high-risk EC patients for micrometastases utilizing immunohistochemistry techniques. Half of this group of patients are still at risk of lymph node metastases even if routine histological findings are negative for metastases. The finding of micrometastases can change therapeutic decisions for the better by incorporating adjuvant treatment options.