Clinical specificities of 246 Japanese with prostate anomalies: early bone metastases, aplastic anemia, lymphatic-related lung lesions, primary pleural and lung cancers, and fatty liver with insulin-resistant diabetes, which were related to prostate fusion gene anomalies

Abstract

A total of 246 Japanese composed of 121 with benign prostatic hyperplasia (BPH) and 125 with prostatic cancer (PCa) were analyzed clinically to explain fusion gene anomalies between erythroblast transformation-specific family transcription factor-related gene (ERG) and transmembrane protease serine 2 (TMPRSS2) on chromosome 21q22. Among the 246 cases, 12 (10%) BPH and 18 (14%) PCa showed prostate-specific antigen (PSA) values of >20 ng/ml. It was shown that PSA was not only secreted from the prostates of BPH and PCa, but also actively from bone metastases, which occurred in the 18 PCa, although PCa bone metastases through lymphatic vessels were shown to be blocked by a cystic abscess formation or skin lipoma derived from lymphatic vessels. Among the 30 cases of >20 ng/ml PSA, lymphatic-related lung lesions were observed in 4 (33%) BPH and 12 (67%) PCa. Except for 1 case with pleural PCa metastasis, pleural, lung, and liver metastases were not observed in the 125 PCa. Instead, primary pleural squamous cell carcinoma was detected in two BPH and one PCa and primary lung adenocarcinoma/lung neuroendocrine cell carcinoma (LNCC) was detected in two BPH and five PCa in which adenocarcinoma changes to LNCC were shown. Besides early PCa bone metastases, hematopoietic normal stem cell suppression was observed in two BPH and two PCa, probably on the basis of periosteal stem cell activation. The correlation between insulin and blood sugar (BS) was examined in 66 BPH and 24 PCa. A negative correlation coefficient of −0.297 was calculated in the nine PCa with abnormal BS. Among 23 PCa and 52 BPH of the 90 cases measured insulin, 10 (43%) PCa and 7 (13%) BPH were diagnosed with diffuse fatty liver. Insulin-resistant diabetes mellitus was observed with a high spike of insulin. High levels of triglyceride and total cholesterol (TC) were well improved by prostatectomy. The TMPRSS2:ERG gene fusions/deletions had caused bone marrow and fat metabolism anomalies and other primary cancers not only in PCa, but also in BPH, which indicated a better prognosis of early prostatectomy.