High-grade prostatic intraepithelial neoplasia

Bostwick, David G.; Qian, Junqi

doi:10.1038/sj.modpathol.3800053

Cited by 58 publications

(89 citation statements)

References 96 publications

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“…Rabbit preimmune IgG control using another adjacent section was negative. The progression of HGPIN to cancer is associated with progressive disruption of the basal cell layer and focal loss of the basement membrane [27]. Our current findings are analogous to our previous studies in breast cancer that show the highest expression of MMP-26 and TIMP-4 in DCIS, with lower expression present in normal breast epithelium and invasive cancer [13].…”

Section: Figuresupporting

confidence: 89%

Coordinated peak expression of MMP-26 and TIMP-4 in preinvasive human prostate tumor

et al. 2006

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The identification of novel biomarkers for early prostate cancer diagnosis is highly important because early detection and treatment are critical for the medical management of patients. Disruption in the continuity of both the basal cell layer and basement membrane is essential for the progression of high-grade prostatic intraepithelial neoplasia (HGPIN) to invasive adenocarcinoma in human prostate. The molecules involved in the conversion to an invasive phenotype are the subject of intense scrutiny. We have previously reported that matrix metalloproteinase-26 (MMP-26) promotes the invasion of human prostate cancer cells via the cleavage of basement membrane proteins and by activating the zymogen form of MMP-9. Furthermore, we have found that tissue inhibitor of metalloproteinases-4 (TIMP-4) is the most potent endogenous inhibitor of MMP-26. Here we demonstrate higher (p<0.0001) MMP-26 and TIMP-4 expression in HGPIN and cancer, compared to non-neoplastic acini. Their expression levels are highest in HGPIN, but decline in invasive cancer (p<0.001 for each) in the same tissues. Immunohistochemical staining of serial prostate cancer tissue sections suggests colocalization of MMP-26 and TIMP-4. The present study indicates that MMP-26 and TIMP-4 may play an integral role during the conversion of HGPIN to invasive cancer and may also serve as markers for early prostate cancer diagnosis.

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Section: Figuresupporting

confidence: 89%

Coordinated peak expression of MMP-26 and TIMP-4 in preinvasive human prostate tumor

et al. 2006

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“…In contrast, nuclear NF-kB staining was identified in scattered basal cells of normal glands and was undetected in luminal cells. We also analysed NF-kB expression in high-grade PIN lesions, which are considered as precursors of prostate cancer (Ashida et al, 2004;Bostwick and Qian, 2004). The 13 PIN specimens showed cytoplasmic immunoreactivity of strong intensity in the vast majority of epithelial cells.…”

Section: Resultsmentioning

confidence: 99%

Activation of nuclear factor-κB in human prostate carcinogenesis and association to biochemical relapse

et al. 2005

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Nuclear factor (NF)-kB/p65 regulates the transcription of a wide variety of genes involved in cell survival, invasion and metastasis. We characterised by immunohistochemistry the expression of NF-kB/p65 protein in six histologically normal prostate, 13 high-grade prostatic intraepithelial neoplasia (PIN) and 86 prostate adenocarcinoma specimens. Nuclear localisation of p65 was used as a measure of NF-kB active state. Nuclear localisation of NF-kB was only seen in scattered basal cells in normal prostate glands. Prostatic intraepithelial neoplasias exhibited diffuse and strong cytoplasmic staining but no nuclear staining. In prostate adenocarcinomas, cytoplasmic NF-kB was detected in 57 (66.3%) specimens, and nuclear NF-kB (activated) in 47 (54.7%). Nuclear and cytoplasmic NF-kB staining was not correlated (P ¼ 0.19). By univariate analysis, nuclear localisation of NF-kB was associated with biochemical relapse (P ¼ 0.0009; log-rank test) while cytoplasmic expression did not. On multivariate analysis, serum preoperative prostate specific antigen (P ¼ 0.02), Gleason score (P ¼ 0.03) and nuclear NF-kB (P ¼ 0.002) were independent predictors of biochemical relapse. These results provide novel evidence for NF-kB/p65 nuclear translocation in the transition from PIN to prostate cancer. Our findings also indicate that nuclear localisation of NF-kB is an independent prognostic factor of biochemical relapse in prostate cancer.

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“…Premalignant dysplastic lesions (prostatic intraepithelial neoplasia, PIN) are characterized by enlarged nuclei, decline in basal epithelial layer, and proliferation and abnormal differentiation of secretory cells. PIN is regarded as pre-invasive stage of prostatic adenocarcinoma [16,19].…”

Section: The Effect Of Aging On Sexual Organsmentioning

confidence: 99%

Effects of aging on the male reproductive system

Güneş

Hekim

Arslan

et al. 2016

J Assist Reprod Genet

196

118

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The study aims to discuss the effects of aging on the male reproductive system. A systematic review was performed using PubMed from 1980 to 2014. Aging is a natural process comprising of irreversible changes due to a myriad of endogenous and environmental factors at the level of all organs and systems. In modern life, as more couples choose to postpone having a child due to various socioeconomic reasons, research for understanding the effects of aging on the reproductive system has gained an increased importance. Paternal aging also causes genetic and epigenetic changes in spermatozoa, which impair male reproductive functions through their adverse effects on sperm quality and count as, well as, on sexual organs and the hypothalamic-pituitarygonadal axis. Hormone production, spermatogenesis, and testes undergo changes as a man ages. These small changes lead to decrease in both the quality and quantity of spermatozoa. The offspring of older fathers show high prevalence of genetic abnormalities, childhood cancers, and several neuropsychiatric disorders. In addition, the latest advances in assisted reproductive techniques give older men a chance to have a child even with poor semen parameters. Further studies should investigate the onset of gonadal senesce and its effects on aging men.

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High-grade prostatic intraepithelial neoplasia

Cited by 58 publications

References 96 publications

Coordinated peak expression of MMP-26 and TIMP-4 in preinvasive human prostate tumor

Coordinated peak expression of MMP-26 and TIMP-4 in preinvasive human prostate tumor

Activation of nuclear factor-κB in human prostate carcinogenesis and association to biochemical relapse

Effects of aging on the male reproductive system

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