PMID- 8529469 OWN - NLM STAT- MEDLINE DCOM- 19960129 LR - 20141120 IS - 0196-4763 (Print) IS - 0196-4763 (Linking) VI - 21 IP - 1 DP - 1995 Sep 1 TI - Heterogeneity of chromosome 17 and erbB-2 gene copy number in primary and metastatic bladder cancer. PG - 40-6 AB - To study the relationship of tumor genomic heterogeneity with bladder cancer phenotype and p53 gene alterations, 138 primary bladder tumors were examined by dual labeling fluorescence in situ hybridization (FISH) using probes for chromosome 17 centromere (p17H8) and p53 (17p13.1). The number of different aneusomic populations > 5% (and monosomic populations > 20%) of cells served as a marker for heterogeneity. Nuclear p53 overexpression and Ki67 labeling index (Ki67 LI) were determined by immunohistochemistry. The number of aneusomic populations was 0 in 53 tumors, 1 in 18, 2 in 47, 3 in 9, and > 3 in 11 tumors. Presence of aneusomy was associated with tumor grade and stage (P < 0.0001 each). Ki67 LI was low in disomic tumors (11.0 +/- 7.7), higher in tumors with 1-3 aneusomic populations (17.4 +/- 11.3), and highest in tumors with > 3 aneusomic populations (25.8 +/- 10.9; P = 0.02 for > 3 vs. 1-3 populations). Aneusomy and heterogeneity were associated with p53 alterations. Aneusomy was seen in 35% of tumors with neither p53 expression nor p53 deletion but in 97% of tumors with both p53 deletion and expression. Nine of 11 tumors with > 3 aneusomic populations exhibited both p53 deletion and overexpression. To study genomic heterogeneity in tumor progression, two recurrences and three metastases of a tumor with known erbB-2 amplification were examined for centromere 17 and erbB-2 copy number. A considerable heterogeneity in centromere 17 and erbB-2 gene copy number was found in both recurrences and metastases, indicating a marked genomic instability in these metastatic cells.(ABSTRACT TRUNCATED AT 250 WORDS) FAU - Sauter, G AU - Sauter G AD - Institute for Pathology, University of Basel, Switzerland. FAU - Moch, H AU - Moch H FAU - Gasser, T C AU - Gasser TC FAU - Mihatsch, M J AU - Mihatsch MJ FAU - Waldman, F M AU - Waldman FM LA - eng GR - CA47537/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Cytometry JT - Cytometry JID - 8102328 RN - 0 (Fluorescent Dyes) RN - 0 (Tumor Suppressor Protein p53) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM MH - Carcinoma, Transitional Cell/*genetics/*secondary MH - Cell Division/genetics MH - Chromosomes, Human, Pair 17/*genetics MH - Fluorescent Dyes MH - Gene Deletion MH - Gene Dosage MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization MH - *Population MH - Receptor, ErbB-2/*genetics MH - Recurrence MH - Tumor Suppressor Protein p53/genetics MH - Urinary Bladder Neoplasms/*genetics/pathology/*secondary EDAT- 1995/09/01 00:00 MHDA- 1995/09/01 00:01 CRDT- 1995/09/01 00:00 PHST- 1995/09/01 00:00 [pubmed] PHST- 1995/09/01 00:01 [medline] PHST- 1995/09/01 00:00 [entrez] AID - 10.1002/cyto.990210109 [doi] PST - ppublish SO - Cytometry. 1995 Sep 1;21(1):40-6. doi: 10.1002/cyto.990210109.