Electron Microscopic Identification of Distant Metastatic Cell in Human Prostate Cancer in Tissue section

Abstract

Mutation in chromatin/DNA/genes of stem cells is a prerequisite for the development of cancer in the benign prostate. Mutation imparts chronic proliferation advantage to invasive and metastatic cancer cells, but not in benign prostate. We hypothesize that identification of metastatic prostatic cancer (PC) cells in tissue sections can lead to an early diagnosis and treatment of patients, hopefully, reducing death due to this disease. We have tested our hypothesis using biopsy and/or radical prostatectomy specimens of untreated and DES (diethylstilbestrol)-treated prostate cancer and transmission electron microscopy. Materials and methods: Tissue samples embedded in Epon were thin sectioned and examined on RCA EMU 3 or 4 transmission electron microscope. Results: We have identified two types of PC stem cells. Invasive stem cell invades the adjacent stroma whereas metastatic cell, a lineage of stem cell, is dedifferentiated columnar/cuboidal cells. Metastatic cell is identified by nuclear plasticity (pleomorphic nucleus), loss of nuclear membranes, loss of boundary between nucleus and cytoplasm and presence of electron dense molecules. Nuclear chromatin/DNA appears as electron dense molecules which readily pass plasma and basement membranes and enter the capillary before adhering to the red cell surface. Electron dense molecules are found in capillary, undoubtedly, reach metastatic site (s). Discussion and conclusion: Chromatin/DNA are small molecules that can readily cross many barriers, unlike an individual cancer cell. We show that invasive a cell is stem cell and metastasis develops from dedifferentiated columnar/cuboidal nuclear electron dense molecules. This is the first study to cells characterize metastatic cell in tissue sections.