PMID- 19893027 OWN - NLM STAT- MEDLINE DCOM- 20100225 LR - 20231213 IS - 1525-2191 (Electronic) IS - 0002-9440 (Print) IS - 0002-9440 (Linking) VI - 175 IP - 6 DP - 2009 Dec TI - Fluorescence in situ hybridization markers for prediction of cervical lymph node metastases. PG - 2637-45 LID - 10.2353/ajpath.2009.090289 [doi] AB - The presence of lymph node metastases is associated with poor prognosis in early stage cervical cancer. As of yet, no molecular markers predicting lymph node metastases have been identified. We examined single genetic markers and a composite marker, comprised of three fluorescence in situ hybridization (FISH) probes targeting the genes LAMP3, PROX1, and PRKAA1, in pretreatment cervical biopsies from 16 lymph node positive cases and 15 lymph node negative controls from women with stage IB and IIA cervical cancer. In addition, we determined clonal patterns by including CCND1 to compare the clonal constitution of primary tumors and associated lymph node metastases. The composite FISH marker allowed for classification of patients into those with and without lymph node metastases with a sensitivity and specificity of 75% and 87%, respectively (P = 0.001). The positive predictive value and negative predictive value were 86% and 76%, respectively. Clonal patterns varied among the tumors. In many cases, changes between the primary tumor and lymph node metastases in the most common clones may indicate that certain clones have a growth advantage for establishing metastases in lymph nodes. We conclude that the composite FISH marker may be useful for determining risk for subsequent development of lymph node metastases in patients with cervical cancer. FAU - Wangsa, Darawalee AU - Wangsa D AD - Department of Oncology-Pathology, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden. FAU - Heselmeyer-Haddad, Kerstin AU - Heselmeyer-Haddad K FAU - Ried, Patricia AU - Ried P FAU - Eriksson, Elina AU - Eriksson E FAU - Schaffer, Alejandro A AU - Schaffer AA FAU - Morrison, Larry E AU - Morrison LE FAU - Luo, Juhua AU - Luo J FAU - Auer, Gert AU - Auer G FAU - Munck-Wikland, Eva AU - Munck-Wikland E FAU - Ried, Thomas AU - Ried T FAU - Lundqvist, Elisabeth Avall AU - Lundqvist EA LA - eng GR - Intramural NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Intramural PT - Research Support, Non-U.S. Gov't DEP - 20091105 PL - United States TA - Am J Pathol JT - The American journal of pathology JID - 0370502 RN - 0 (Biomarkers, Tumor) RN - 0 (CCND1 protein, human) RN - 0 (Homeodomain Proteins) RN - 0 (LAMP3 protein, human) RN - 0 (Lysosomal Membrane Proteins) RN - 0 (Neoplasm Proteins) RN - 0 (Tumor Suppressor Proteins) RN - 0 (prospero-related homeobox 1 protein) RN - 136601-57-5 (Cyclin D1) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) RN - EC 2.7.11.31 (PRKAA1 protein, human) SB - IM MH - AMP-Activated Protein Kinases/biosynthesis/genetics MH - Adult MH - Aged MH - Biomarkers, Tumor/*genetics MH - Cyclin D1/biosynthesis/genetics MH - Female MH - Homeodomain Proteins/biosynthesis/genetics MH - Humans MH - *In Situ Hybridization, Fluorescence MH - Lymphatic Metastasis/*pathology MH - Lysosomal Membrane Proteins/biosynthesis/genetics MH - Middle Aged MH - Neoplasm Proteins/biosynthesis/genetics MH - Neoplasm Staging MH - ROC Curve MH - Sensitivity and Specificity MH - Tumor Suppressor Proteins/biosynthesis/genetics MH - Uterine Cervical Neoplasms/*genetics/*pathology PMC - PMC2789632 EDAT- 2009/11/07 06:00 MHDA- 2010/02/26 06:00 PMCR- 2010/12/01 CRDT- 2009/11/07 06:00 PHST- 2009/11/07 06:00 [entrez] PHST- 2009/11/07 06:00 [pubmed] PHST- 2010/02/26 06:00 [medline] PHST- 2010/12/01 00:00 [pmc-release] AID - S0002-9440(10)60771-7 [pii] AID - 10.2353/ajpath.2009.090289 [doi] PST - ppublish SO - Am J Pathol. 2009 Dec;175(6):2637-45. doi: 10.2353/ajpath.2009.090289. Epub 2009 Nov 5.