PMID- 19861998 OWN - NLM STAT- MEDLINE DCOM- 20091113 LR - 20211020 IS - 1532-1827 (Electronic) IS - 0007-0920 (Print) IS - 0007-0920 (Linking) VI - 101 IP - 9 DP - 2009 Nov 3 TI - Intraepithelial CD8-positive T lymphocytes predict survival for patients with serous stage III ovarian carcinomas: relevance of clonal selection of T lymphocytes. PG - 1513-21 LID - 10.1038/sj.bjc.6605274 [doi] AB - BACKGROUND: The aim of this study was to investigate the prognostic effect of tumour-infiltrating lymphocytes (TILs) in serous stage III ovarian carcinoma to determine TIL clonality and to correlate this to Her2/neu expression. METHODS: Formalin-fixed and paraffin-embedded ovarian carcinomas were examined for CD20-, CD3-, CD4- and CD8-positive lymphocytes (n=100), and for Her2/neu-positive tumour cells (n=55/100) by immunohistochemistry. Clonality analysis was carried out by T-cell receptor gamma (TCRgamma) gene rearrangements (n=93/100). Statistical analyses included experimental and clinico-pathological variables, as well as disease-free (DFS) and overall (OS) survival. RESULTS: CD20-positive B lymphocytes were present in 57.7% (stromal)/33.0% (intraepithelial) and CD3-positive T lymphocytes in 99.0% (stromal)/90.2% (intraepithelial) of ovarian carcinomas. Intraepithelial CD3-positive T lymphocytes were correlated with improved DFS in optimally debulked patients (P=0.0402). Intraepithelial CD8-positive T lymphocytes were correlated with improved OS in all optimally debulked patients (P=0.0201) and in those undergoing paclitaxel/carboplatin therapy (P=0.0092). Finally, rarified and clonal TCRgamma gene rearrangements were detected in 37 out of 93 (39.8%) and 15 out of 93 (16.1%) cases, respectively. This was marginally associated with improved DFS (P=0.0873). Despite a significant correlation of HER2/neu status and intraepithelial CD8-positive lymphocytes (P=0.0264), this was non-directional (R=-0.257; P=0.0626). CONCLUSION: Improved survival of ovarian cancer patients is related to the infiltration, clonal selection and intraepithelial persistence of T lymphocytes. FAU - Stumpf, M AU - Stumpf M AD - Department of Obstetrics and Gynecology, Albert-Ludwigs-University, Freiburg 79106, Germany. FAU - Hasenburg, A AU - Hasenburg A FAU - Riener, M-O AU - Riener MO FAU - Jutting, U AU - Jutting U FAU - Wang, C AU - Wang C FAU - Shen, Y AU - Shen Y FAU - Orlowska-Volk, M AU - Orlowska-Volk M FAU - Fisch, P AU - Fisch P FAU - Wang, Z AU - Wang Z FAU - Gitsch, G AU - Gitsch G FAU - Werner, M AU - Werner M FAU - Lassmann, S AU - Lassmann S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090929 PL - England TA - Br J Cancer JT - British journal of cancer JID - 0370635 RN - EC 2.7.10.1 (ERBB2 protein, human) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - CD8-Positive T-Lymphocytes/*immunology MH - Female MH - Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor MH - Humans MH - Lymphocytes, Tumor-Infiltrating/*immunology MH - Middle Aged MH - Neoplasm Staging MH - Ovarian Neoplasms/*immunology/*mortality/pathology MH - Receptor, ErbB-2/analysis PMC - PMC2778517 EDAT- 2009/10/29 06:00 MHDA- 2009/11/17 06:00 PMCR- 2010/11/03 CRDT- 2009/10/29 06:00 PHST- 2009/10/29 06:00 [entrez] PHST- 2009/10/29 06:00 [pubmed] PHST- 2009/11/17 06:00 [medline] PHST- 2010/11/03 00:00 [pmc-release] AID - 6605274 [pii] AID - 10.1038/sj.bjc.6605274 [doi] PST - ppublish SO - Br J Cancer. 2009 Nov 3;101(9):1513-21. doi: 10.1038/sj.bjc.6605274. Epub 2009 Sep 29.