title: Diagnostic value of DNA alteration: loss of heterozygosity or allelic imbalance-promising for molecular staging of prostate cancers.
abstract: The biological behavior of prostate cancer is uncertain, and therefore, search for molecular prognostic markers associated with disease progression seems to be essential. We performed microsatellite allelotyping of DNA isolated from primary prostate tumors biopsies (prostate adenocarcinoma, PCa). We evaluated the frequency of allelic imbalance (AI), including loss of heterozygosity and/or microsatellite imbalance (LOH/MSI) as well as the association of these DNA alterations with clinicopathological variables. We assessed the significance of LOH/MSI alterations in selected imprinted and non-imprinted chromosomal regions (IR and NIR) in PCa. A total of 50 biopsies of prostate tumor (containing >75 % tumor cells) were histologically examined confirming prostate carcinoma. Microsatellite allelotyping using 16 microsatellite markers linked to the following chromosomal regions: 1p31.2, 3p21.3-25.3, 7q32.2, 9p21.3, 11p15.5, 12q23.2, and 16q22.1 was performed. The incidence of LOH/MSI alterations in prostate tumor cells was the highest for chromosomal regions 7q32.2 and 16q22.1 (31.25 and 26.60 %, respectively), followed by 1p31.2 and 3p21.3-25.3 (26.50 and 17.40 %, respectively). Statistically significant increase in LOH/MSI alterations has been observed for markers: D1S2137 (1p region; p = 0.00032), D9S974 (9p region; p = 0.0017), and D16S3025 (16q region; p = 0.0017). Statistically significant differences in frequency of LOH/MSI alterations in particular chromosomal regions have been found for 1p31.2, 7q32.2 and 16q22.1 (p = 0.027, p = 0.012 and p = 0.031, respectively). We documented statistically significant association between Fractional Allele Loss (FAL) index and advanced tumor stage (p < 0.05). We suggest that genomic instability of LOH/MSI type is a frequent event in prostate carcinogenesis and assessed as FAL index has clinical value for the molecular staging of prostate cancer in (TRUS)-guided prostate biopsy material.
authors.affiliation: Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Łódź, Pomorska St. 141/143, 90-236 Lodz, Poland. zreg@biol.uni.lodz.pl
authors.forename: Magdalena
authors.initials: M
authors.lastname: Bryś
authors.forename: Monika
authors.initials: M
authors.lastname: Migdalska-Sęk
authors.forename: Dorota
authors.initials: D
authors.lastname: Pastuszak-Lewandoska
authors.forename: Ewa
authors.initials: E
authors.lastname: Forma
authors.forename: Karolina
authors.initials: K
authors.lastname: Czarnecka
authors.forename: Daria
authors.initials: D
authors.lastname: Domańska
authors.forename: Ewa
authors.initials: E
authors.lastname: Nawrot
authors.forename: Jacek
authors.initials: J
authors.lastname: Wilkosz
authors.forename: Waldemar
authors.initials: W
authors.lastname: Różański
authors.forename: Ewa
authors.initials: E
authors.lastname: Brzeziańska
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology*; D000368:Aged; D022981:Allelic Imbalance; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D009367:Neoplasm Staging / Q000379:methods*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D004273:DNA, Neoplasm