Clinicopathological Significance of Extranodal Adipose Tissue Invasion in Metastatic Lymph Nodes in Patients With Prostate Cancer

Background: Lymph node (LN) metastasis is a poor prognostic factor in patients with prostate cancer. Elucidating the mechanisms underlying cancer progression in the metastatic microenvironment of LNs is crucial to establishing novel therapies. Adipocytes interact with cancer cells and regulate cancer progression. In this study, we aimed to clarify the clinicopathological significance of extranodal adipose tissue invasion in metastatic LNs and preoperative adipokine concentration in patients with prostate cancer exhibiting metastatic LNs. Methods: We examined the pathological findings of primary and metastatic nodes and clinical information of 66 specimens from 46 patients with prostate cancer. A sub-analysis was performed to assess the relationship between preoperative adiponectin/leptin concentrations and clinical/pathological findings in the blood samples of 56 patients with prostate cancer who either did or did not show LN metastasis. Results: The number of metastatic LNs in patients correlated with the involvement of adipose tissue and lymphovascular invasion (p = 0.039 and < 0.001, respectively). Preoperative adiponectin concentration was lower in patients with resected margin-positive and extraprostatic extension-positive primary cancers (p = 0.0071 and 0.02, respectively). Preoperative adiponectin concentrations were significantly lower in patients with metastatic LNs than in patients without LN metastasis (p < 0.001). Moreover, leptin concentrations were significantly higher in patients with metastatic LNs than in patients without LN metastasis (p < 0.001). In patients with metastatic LNs, preoperative adiponectin concentrations were significantly lower in patients with biochemical recurrence than in patients without biochemical recurrence (p = 0.031). There was no correlation between biochemical recurrence and pathological findings. Conclusions: This is the first report on the detailed histopathological characteristics of prostate cancer with LN metastases and the significance of preoperative adiponectin concentration in predicting the pathological features of primary cancers. Also, adipokines are a significant prediction factor of LN metastases for prostate cancer patients. Adipose tissue and adipose-secreting factors may be involved in the progression of metastatic and primary prostate cancer.