Multiphoton gradient index endoscopy for evaluation of diseased human prostatic tissue ex vivo.

Multiphoton microscopy can instantly visualize cellular details in unstained tissues. Multiphoton probes with clinical potential have been developed. This study evaluates the suitability of multiphoton gradient index (GRIN) endoscopy as a diagnostic tool for prostatic tissue. A portable and compact multiphoton endoscope based on a 1-mm diameter, 8-cm length GRIN lens system probe was used. Fresh ex vivo samples were obtained from 14 radical prostatectomy patients and benign and malignant areas were imaged and correlated with subsequent H&E sections. Multiphoton GRIN endoscopy images of unfixed and unprocessed prostate tissue at a subcellular resolution are presented. We note several differences and identifying features of benign versus low-grade versus high-grade tumors and are able to identify periprostatic tissues such as adipocytes, periprostatic nerves, and blood vessels. Multiphoton GRIN endoscopy can be used to identify both benign and malignant lesions in ex vivo human prostate tissue and may be a valuable diagnostic tool for real-time visualization of suspicious areas of the prostate.

Deficiency of DNA repair nuclease ERCC1-XPF promotes prostate cancer progression in a tissue recombination model.

BACKGROUND: The excision repair cross complementing (ERCC1) gene product plays a vital role in the nucleotide excision repair (NER) and DNA interstrand crosslink repair pathways, which protect the genome from mutations and chromosomal aberrations, respectively. Genetic deletion of Ercc1 in the mouse causes dramatically accelerated aging. We examined the effect of Ercc1 deletion in the development of prostate cancer in a prostate recapitulation model as Ercc1 deficient mice die within four weeks of birth. METHODS: Prostate tissues from Ercc1(-/-) mice or wild-type littermates were combined with embryonic rat urogenital mesenchyme and grown as renal grafts for a total of 8, 16, and 24 weeks before histological, expression and proliferative evaluation. RESULTS: Invasive adenocarcinoma was observed in Ercc1(-/-) tissue recombinants but not wild-type as early as 8 weeks post-grafting. PIN-like lesions in Ercc1(-/-) tissue recombinants had more cytologic and architectural atypia than wild-type (P = 0.02, P = 0.0065, and P = 0.0003 at the 8, 16, and 24 weeks, respectively), as well as more proliferative cells (P = 0.022 and P = 0.033 at 8 and 16 weeks, respectively). With serial grafting, Ercc1(-/-) tissue recombinants progressed to a more severe histopathological phenotype more rapidly than wild-type (P = 0.011). CONCLUSIONS: Results show that ERCC1 and by implication the NER and/or interstrand crosslink repair mechanisms protect against prostate carcinogenesis and mutations or polymorphisms affecting these DNA repair pathways may predispose prostate epithelial cells to transformation.