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 ¼ 100), and for Her2/neu-positive tumour cells (n ¼ 55/100) by immunohistochemistry. Clonality analysis was carried out by T-cell receptor g (TCRg) gene rearrangements (n ¼ 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 ¼ 0.0402). Intraepithelial CD8-positive T lymphocytes were correlated with improved OS in all optimally debulked patients (P ¼ 0.0201) and in those undergoing paclitaxel/carboplatin therapy (P ¼ 0.0092). Finally, rarified and clonal TCRg 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 ¼ 0.0873). Despite a significant correlation of HER2/neu status and intraepithelial CD8-positive lymphocytes (P ¼ 0.0264), this was non-directional (R ¼ À0.257; P ¼ 0.0626). CONCLUSION: Improved survival of ovarian cancer patients is related to the infiltration, clonal selection and intraepithelial persistence of T lymphocytes.
Hepatocellular carcinomas (HCC) and bile duct carcinomas (BDC) have a poor prognosis since they are often detected at advanced stages and respond poorly to adjuvant therapy. Serum markers (e.g. AFP, CA19-9, etc.) can be used for early detection of these tumours but have only moderate sensitivity and specificity. The Golgi-associated protein GOLPH2 was found in the tissue and serum of patients with HCC and CCC and might be used to detect these tumours in time. The biopsy still remains the gold standard in the diagnosis of HCC and CCC. When biopsies are taken from these tumours they are often fragmented and contain reactive changes. Therefore immunohistochemical markers can aid in excluding or ascertaining malignancy. Studies have shown that the oncofetal protein "IGF-II mRNA-binding protein 3" (IMP3), the cell adhesion molecules P-cadherin and CD24, the cancer testis antigen MAGE-C2/CT-10 as well as the protein periostin can be used as tissue markers in the diagnosis of HCC and CCC.
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