Molecular biology of prostatic intraepithelial neoplasia

Abstract

ABSTRACT:High-grade PIN is the most likely precursor of prostatic adenocaranoma, according to virtually all available evidence to date. The clinical importance of recognizing PIN is based on its strong association with prostatic carcinoma. PIN has a high predictive value as a marker for adenocarcinoma. Its identification in biopsy specimens of the prostate warrants further search for concurrent invasive carcinoma.PIN is associated with progressive abnormalities of phenotype and genotype intermediate between normal prostatic epithelium and cancer, indicating impairment of cell differentiation and regulatory control with advancing stages of prostatic carcinogenesis. There is progressive gain or loss of a wide variety of biomarkers, including morphometric markers, differentiation markers, stromal markers, growth factors and associated receptors, oncogenes, tumor suppressor genes, and chromosomes. Abnormalities in expression of most biomarkers are amplified in the progression from high-grade PIN to localized cancer, metastatic cancer, and hormone-refractory cancer. Oncogenesis of prostatic carcinoma probably occurs through the selection of several genetic changes, each modifymg the expression or function of genes controlling cell growth and differentiation. Further studies are needed to evaluate the function and prognostic value of oncogene expression in the normal, preneoplastic, and neoplastic prostate. 0 1996 Wiley-Liss, Inc.

Apoptosis and nuclear shapes in benign prostate hyperplasia and prostate adenocarcinoma: Comparison with and relation to Gleason score

“…12 In PCA, the number of apoptotic bodies varied with cell type, being 1.7% for solid undifferentiated carcinomas, 25.2% for small cell undifferentiated carcinomas and 5.5% for prostatic transitional cell carcinomas. 14 In accordance with results from most previous studies, the present study showed a higher frequency of apoptotic bodies in PCA than in BPH and, also, the higher the Gleason score for PCA, the higher the frequency of apoptosis.…”

“…It is generally recognized that the frequency of apoptotic bodies increases from BPH through prostatic intraepithelial neoplasia (PIN) to PCA. [12][13][14] It can be explained, in part, by the fact that increased expression of apoptosis-related genes, including transforming growth factor-b1, was associated with induced mouse PCA compared with BPH. 15 The positive correlation between the frequency of apoptotic bodies and Gleason grade can be partly explained by significant differences in the longevity of apoptotic bodies compared with mitotic bodies.…”

Ornithine Decarboxylase Is Sufficient for Prostate Tumorigenesis via Androgen Receptor Signaling

“…44 Several gene alterations, such as decreased GSTP1 and Nkx3.1 expression, have been implicated in the malignant transformation of normal prostate epithelium to HGPIN. 45 HGPIN is a precursor of invasive prostate carcinoma, 46,47 but little is known about the genetic events involved in the advancement to invasive disease, 48,49 a sequence of events that remains unclear. 50 Few studies have shown specific genetic alterations in HGPIN, including in the SIRT1/S6K axis, mTOR-RAPTOR pathway, PEDF, and miR-21, 51e54 but much remains unexplained.…”

High-grade prostatic intraepithelial neoplasia

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] PIN is the abnormal proliferation within the prostatic ducts, ductules, and large acini of premalignant foci of cellular dysplasia and carcinoma in situ without stromal invasion. [18][19][20] The diagnostic term 'prostatic intraepithelial neoplasia' has been endorsed at multiple multidisciplinary and pathology consensus meetings, 6,14,[21][22][23][24] and the interobserver agreement between pathologists has been determined to be 'good to excellent' 25,26 for high-grade PIN.…”

“…31,63,64 Increasing rates of aneuploidy and angiogenesis as the grade of PIN progresses are further evidence that high-grade PIN is a precancer. 1,62,[65][66][67][68] Prostate cancer and high-grade PIN also have similar proliferative and apoptotic indices. 1,3,40,[69][70][71][72][73][74] It is often difficult with small foci in needle biopsies to separate cancer from suspicious foci (atypical small acinar proliferation suspicious for but not diagnostic of malignancy) when there is coexistent high-grade PIN; the difficulty is based on the inability to separate tangential cutting of the larger pre-existing acini of PIN (that may appear as small separate adjacent acini) from the smaller discrete acini of cancer.…”