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Fisher Biomarker Research Laboratory


Rudolf Virchow published in 1863 his famous aphorism "omnis cellula e cellula"("every cell stems from another cell") and he launched the field of cellular pathology and stated that all diseases involve changes in normal cells, that is, all pathology ultimately is cellular pathology.  Further, for over 140 years it has been shown that nuclear morphology is often disrupted in cancer. In the 1860s, Lionel S. Beale of King’s College Hospital examined unstained sputum from a patient with cancer of the pharynx and observed nuclear morphology variations in the cancerous cells. Lionel Beale also established a private laboratory near the King’s College Hospital and gave a course of lectures on "The Microscope in Medicine"which included demonstrations in clinical pathology.  

A Cancer (CaP) usually is the result of a multistep process and prostate cancer (CaP) is not different. This evolution includes initiation, which occurs through various aging events and multiple insults (such as chronic infection, inflammation and genetic instability through reactive oxygen species causing DNA double-strand breaks), followed by a multistep process of progression. These steps include several genetic and epigenetic alterations, as well as alterations to the chromatin structure, which occur in response to the carcinogenic stress-related events that sustain proliferative signaling. Events such as evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis are readily observed. In addition, in conjunction with these critical drivers of carcinogenesis, other factors related to the etiopathogenesis of CaP, involving energy metabolism and evasion of the immune surveillance system, appear to be involved. In addition, when cancer spread and metastasis occur, the ‘tumor microenvironment’ in the bone of CaP patients may provide a way to sustain dormancy or senescence and eventually establish a 'seed and soil' site where CaP proliferation and growth may occur over time. When CaP is initiated and progression ensues, significant alterations in nuclear size, shape and heterochromatin (DNA transcription) organization are found, and key nuclear transcriptional and structural proteins, as well as multiple nuclear bodies can lead to precancerous and malignant changes. These series of cellular and tissue-related malignancy-associated events can be quantified to assess disease progression and management.

FROM: Asian Journal of Andrology (2012) 14, 375–384; doi:10.1038/aja.2011.148; published online 16 April 2012

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