title: Bad seeds produce bad crops: a single stage-process of prostate tumor invasion.
abstract: It is a commonly held belief that prostate carcinogenesis is a multi-stage process and that tumor invasion is triggered by the overproduction of proteolytic enzymes. This belief is consistent with data from cell cultures and animal models, whereas is hard to interpret several critical facts, including the presence of cancer in "healthy" young men and cancer DNA phenotype in morphologically normal prostate tissues. These facts argue that alternative pathways may exist for prostate tumor invasion in some cases. Since degradation of the basal cell layer is the most distinct sign of invasion, our recent studies have attempted to identify pre-invasive lesions with focal basal cell layer alterations. Our studies revealed that about 30% of prostate cancer patients harbored normal appearing duct or acinar clusters with a high frequency of focal basal cell layer disruptions. These focally disrupted basal cell layers had significantly reduced cell proliferation and tumor suppressor expression, whereas significantly elevated degeneration, apoptosis, and infiltration of immunoreactive cells. In sharp contrast, associated epithelial cell had significantly elevated proliferation, expression of malignancy-signature markers, and physical continuity with invasive lesions. Based on these and other findings, we have proposed that these normal appearing duct or acinar clusters are derived from monoclonal proliferation of genetically damaged stem cells and could progress directly to invasion through two pathways: 1) clonal in situ transformation (CIST) and 2) multi-potential progenitor mediated "budding" (MPMB). These pathways may contribute to early onset of prostate cancer at young ages, and to clinically more aggressive prostate tumors.
authors: American Registry of Pathology and Armed Forces Institute of Pathology, Washington DC 20306-6000, USA. man@afip.osd.mil
authors: Yan-gao
authors: YG
authors: Man
authors: William A
authors: WA
authors: Gardner
mesh_terms: D000328:Adult; D049109:Cell Proliferation; D018450:Disease Progression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009361:Neoplasm Invasiveness; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D019998:Racemases and Epimerases / Q000378:metabolism
chemical_list: C081876:CKAP4 protein, human; D008565:Membrane Proteins; D018809:Proliferating Cell Nuclear Antigen; D012334:RNA, Neoplasm; D019998:Racemases and Epimerases; C108352:alpha-methylacyl-CoA racemase